PERINATAL AND FAMILY SERVICES

Prenatal Exposure and Effect on Children

This webpage identifies the major literature in the field of perinatal and family services: prenatal exposure and effect on children. The time frame is from January 2000 through December 2014.

Backes, C. H., Backes, C. R., Gardner, D., Nankervis, C. A., Giannone, PJ., & Cordero, L. (2012). Neonatal abstinence syndrome: transitioning methadone-treated infants from an inpatient to an outpatient setting. Journal of Perinatology, 32(6), pp. 425–430

This study compares the safety and efficacy of a traditional inpatient only approach with a combined in-patient and out-patient methadone treatment program. Based on this study, the authors suggest that a combined inpatient and outpatient methadone treatment in the management of NAS decreases hospital stay and reduces cost. Additional studies are needed to evaluate the potential long-term benefits of the combined approach on infants and their families.

Bagley, S. M., Wachman, E. M., & Holland, E., & Brogly, S. B. (2014). Review of the assessment and management of neonatal abstinence syndrome. Addiction Science & Clinical Practice, 2014, pp. 9-19.

In this article, the authors present the findings of a systematic review examining the available evidence for NAS assessment tools, nonpharmacologic interventions, and pharmacologic management of opioid-exposed infants. The authors found that opioid medications such as morphine or methadone are recommended as first-line therapy, with phenobarbital or clodine, as second-line adjunctive therapy.

Baldacchino, A., Arbuckle, K., Petrie, D. J., & McCowan, C. (2014). Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis. BMC Psychiatry, 14(1), pp. 104.

This article presents the findings of a quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children. The authors found that 5 studies out of 200 identified, reported on neurobehavioral function of children after maternal opioid use during pregnancy. According to these findings, the authors conclude that exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed children, however in all domains, there was a trend of poorer outcomes.

Bandstra, E. S., Morrow, C. E., Mansoor, E., & Accomero, V. H. (2010). Prenatal Drug Exposure: Infant and Toddler Outcomes. Journal of Addictive Diseases, 29(2), pp. 245-258.

In this article, the authors provide an overview of the current literature on the impact of maternal drug use, with a specific focus on opioids and cocaine during pregnancy and the long-term outcomes on infants and toddlers from birth through age 3 years. The findings presented focus on comparing cocaine-exposed with non-exposed infants and toddlers focusing on anthropometric growth, infant neurobehavior, visual and auditory function, and cognitive, motor, and language development.

Barth, R. P., Freudlich, M., & Brodzinsky, D. (Eds.). (2000). Adoption and prenatal alcohol and drug exposure: Research, Policy and Practice. Washington, DC: Child Welfare League of America.

As professionals become aware of the impact of prenatal substance exposure on children in the adoption process or who are available for adoption, there is a heightened need for understanding the range of issues connected with prenatal alcohol and drug exposure. This book addresses many of these issues, providing important information on: the impact of prenatal substance exposure on children’s immediate health and well-being; the long-term implications for the health and development of substance-exposed infants; the role that a positive postnatal environment can play in remediating the effects of prenatal substance exposure; counseling suggestions for prospective adoptive parents regarding the effects of prenatal substance exposure; and the ongoing services and supports that are needed for adoptive families and their substance-exposed children to maximize positive outcomes.

Barth, R. P. (2001). Research outcomes of prenatal substance exposure and the need to review policies and procedures regarding child abuse reporting. Child Welfare, 80(2), pp. 275-296.

Research on the outcomes of drug-exposed children evinces elevated developmental risks from the interaction of subtle biological vulnerabilities and compromised parenting. States, however, have generally not reviewed the procedures and policies they developed in the early 1990s when there was less research and experience with these children. At that time the gravest risks related to perinatal substance exposure seemed to be excessively punitive treatment of mothers by overzealous criminal justice prosecutors. This article discusses primary and secondary risks of prenatal drug exposure. The author also clarifies policy options for reporting and serving children who are born testing positive for controlled substances and calls for strengthening existing state policies regarding child abuse reporting and response.

Bauer, C. R., Langer, J. C., Shankaran, S., Bada, H. S., Lester, B., Wright, L. L., Krause-Steinrauf, M. S…Verter, J. (2005). Acute neonatal effects of cocaine exposure during pregnancy. Archives of Pediatrics & Adolescent Medicine, 159(9), pp. 824-834.

The purpose of this study was to identify associations between cocaine-exposure during pregnancy and medical conditions in newborn infants from birth through hospital discharge. A total of 717 cocaine-exposed infants and 7442 non-exposed infants participated in a multi-site, prospective, randomized study. The authors examined results of physical examination and conditions observed during hospitalization. The study found that cocaine-exposed infants were about 1.2 weeks younger, weighed 536 g less, measured 2.6 cm shorter, and had head circumference 1.5 cm smaller than non-exposed infants. Results did not confirm previously reported abnormalities. Central and autonomic nervous system symptoms were more frequent in the exposed group: jittery/tremors, high-pitched cry, irritability, excessive suck, hyperalertness, and autonomic instability. No differences were detected in organ systems by ultrasound examination. Exposed infants had more infections, including hepatitis, syphilis, and human immunodeficiency virus exposure; were less often breastfed; had more child protective services referrals; and were more often not living with their biological mother. The authors conclude that central and autonomic nervous system symptoms were more frequent in the exposed cohort and persisted in an adjusted analysis. They were usually transient and may be a true cocaine effect. Abnormal anatomic outcomes previously reported were not confirmed. Increased infections, particularly sexually transmitted diseases, pose a serious public health challenge. Exposure increased involvement of child protective services and out-of-home placement.

Bauer, C. R., Lambert, B. L., Bann, C. M., Lester, B. M., Shankaran, S., Bada, H. S., Whitaker, T. M…Higgins, R. D. (2011). Long-term impact of maternal substance use during pregnancy and extrauterine environmental adversity: Stress hormone levels of preadolescent children. Pediatric Research, 70(2), pp. 213-219. DOI: 10.1203/PDR.0b013e3182226e26

This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (n = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. Although repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE.

Belcher, H. M. E, Butz, A. M., Wallace, P., Hoon, A. H., Reinhardt, E., Reeves, S. A., & Pulsifer, M. B. (2005). Spectrum of early intervention services for children with intrauterine drug exposure. Infants and Young Children, 18(1), pp. 2-15.

This article highlights three different approaches utilized by programs to provide early intervention and improve the well-being of parents for parents who have a history of drug dependence and their children. All three programs are community-based, using comprehensive culturally relevant developmental models. The first program, Project STRIVE (Support, Trust, Rehabilitation, Initiative, Values, and Education), provided onsite comprehensive substance abuse treatment, intensive center- and home-based social work, and parent education care for pregnant women with drug dependence and their newborns. The second program, the Early Infant Transition Center, enrolled newborns with a history of neonatal abstinence syndrome and their mothers and provided 24-hour nursing care, on call physicians and nurse practitioners, social workers, parent education, and onsite sleeping accommodation for parents during their infant’s recovery. The third program, Home-U-Go Safely, used community-based nurses to give home-based health monitoring, education, and support to new mothers with a history of cocaine and/or opiate dependence. Data collected from these programs showed significant improvements in maternal/caregiver and child outcomes such as improved parent knowledge, decreased parental stress and better perceptions of their children’s behavior, improved neonatal birth growth parameters including weight and head circumference. The authors point out that interventions for children with intrauterine drug exposure require a comprehensive culturally relevant family-oriented approach. Intervention strategies which address the multiple needs of the drug-dependent mother and the child have the greatest promise in improving overall outcomes.

Berger, L. M, & Waldfogel, J. (2000). Prenatal cocaine exposure: Long-run effects and policy implications. Social Service Review, 74(1), pp. 28-54.

This article reviews the literature regarding prenatal cocaine exposure and child development. The authors reexamine current child welfare policies in light of that literature, paying particular attention to laws that mandate reporting substance-exposed newborns and substance use during pregnancy as well as policies that view such reports as prima facie evidence of child maltreatment. The authors also reassess the utility of such policies, given the current knowledge of the long-term effects of prenatal exposure, and consider alternative approaches to protecting children who are born to parents who are using crack cocaine.

Bersani, I, Corsello, M., Mastandrea, M., Patacchiola, V., Foligno, S., Garofalo, V., & Dotta, A. (2013). Neonatal abstinence syndrome. Early Human Development, 89S4, pp. S85–S87

This article provides a brief and succinct introduction to NAS. The authors give background on drug use during pregnancy and provide safe nursing techniques for mothers wishing to breastfeed their children.

Bhatt-Mehta, V., Ng, C. M., Schumacher, R. E. (2014). Effectiveness of a clinical pathway with methadone treatment protocol for treatment of neonatal abstinence syndrome following in utero drug exposure to substances of abuse. Pediatric Critical Care Medicine: A Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 15(2), pp. 162-169. DOI: 10.1097/PCC.0b013e3182a12611

The aim of this study was to evaluate the effectiveness of methadone for the treatment of neonatal abstinence syndrome (NAS) according to a preexisting clinical pathway. The neonates in this study received methadone for the treatment of neonatal abstinence syndrome according to a predefined clinical treatment pathway and were evaluated for treatment success as defined by adherence to the methadone regimen with no residual signs of withdrawal. The clinical pathway used proved to be insufficient for adequate symptom control.

Bridgett, D., & Mayes, L. C. (2011). Development of inhibitory control among prenatally cocaine exposed and non-cocaine exposed youths from late childhood to early adolescence: The effects of gender and risk and subsequent aggressive behavior. Neurotoxicology and Teratology, 33(1), pp. 47-60.

The goal of the present investigation was to characterize the development of inhibitory control, an aspect of executive functions, in a sample of prenatally cocaine exposed (CE; n = 165) children compared to an at-risk, but prenatally cocaine unexposed (NCE; n = 119) sample across time (i.e. 7.5 to 11.5 years of age). Although all participants improved across development, higher cumulative risk in both groups was associated with slower age-related improvements (i.e. higher slopes) in the time to complete the Stroop task across development. After accounting for gender and cumulative risk, findings in both groups indicated that those who made more errors at 7.5 years of age and/or who had slower age-related changes (i.e. higher slopes) of time to complete the Stroop task across development were more aggressive as rated by caregivers at 14 years of age. Although qualified by gender and cumulative risk, these findings are consistent with reduced cognitive processing efficiency and executive function difficulties in CE children relative to NCE children. Findings suggest that executive function difficulties in CE children may be subtle as development continues to unfold over time. Furthermore, these findings indicate that development of inhibitory control may be an important mechanism linking prenatal cocaine exposure, gender, and cumulative risk to later adverse outcomes.

Broome, L., & So, T. (2012). Neonatal abstinence syndrome: the use of clonidine as a treatment option. Neoreviews, 12(1), pp. e575. DOI: 10.1542/neo.12-10-e575.

This article presents findings of a study on the effects of clonidine as a treatment option for neonatal abstinence syndrome (NAS). The authors argue that the drug has the potential to serve as an option to treat NAS because it is easy to administer, does not require a long tapering period. The authors advise that more long-term studies are needed to determine the efficacy and safety of clonidine in treatment.

Burry, C. L., & Wright, L. (2006). Facilitating visitation for infants with prenatal substance exposure. Child Welfare, 85(6), pp. 899-918.

Permanency planning for infants with prenatal substance exposure is challenging due to characteristics of the infants and the ongoing substance use or relapse of the parents. This article addresses the use of visitation as a child welfare intervention when a child with prenatal substance exposure is in out-of-home care, and discusses special issues in providing such intervention. The authors suggest that although substance use is a critical factor in planning, it cannot be the deciding factor in decision making about permanency. The authors state that the child welfare service of visitation is the primary mechanism through which workers normally deal with issues such as psychological or emotional reactions to separation, improvement of parenting skills, sharing information, and determining and supporting permanency planning. The authors conclude that visitation is no less important when substances are involved and the productive use of visitation for permanency planning depends on workers understanding of how substance use affects the dynamics of visitation and skillfully focusing visits on issues and needs that are particularly relevant to this population.

Burstyn, I., Kapur, N., & Cherry, N. M. (2010). Substance use of pregnant women and early neonatal morbidity: where to focus intervention? Canadian Journal of Public Health, 101(2), pp. 149-53.

Few studies, and none in Canada, have examined the relation between maternal smoking, alcohol consumption and drug dependence during pregnancy and early neonatal morbidity. In this study, the authors analyzed records of singleton live births in Alberta, Canada. Maternal smoking during pregnancy was the most prevalent risk factor, affecting 20% of mothers by self-report, with the figure being possibly twice as high once corrected for under-reporting. Smoking (ORs 1.2), alcohol consumption (ORs 1.2-1.5) and drug dependence (ORs 1.7-2) by the mother during pregnancy were associated with increased risk for each of the markers of early neonatal morbidity (p<0.05, after correcting for covariates). Eliminating the most common among these risk factors, maternal smoking, would prevent 10-15% of each of the three neonatal morbidity markers. Other recorded factors related to mother's pre-conception health, despite some strong associations, were responsible for only a small proportion of cases. We conclude that in preventing early neonatal morbidity among singleton births in Alberta, control of maternal smoking, the most common of the potentially modifiable risk factors, remains an important goal.

Chaplin, T. M., Fahy, T., Sinha, R., & Mayes, L. C. (2009). Emotional arousal in cocaine exposed toddlers: Prediction of behavior problems. Neurotoxicology & Teratology, 31(5), pp. 275-282. DOI: 10.1016/j.ntt.2009.05.002

Prenatal cocaine exposure (PCE) may be associated with alterations in children’s developing emotional arousal and regulation systems. The authors examined emotional responses to a frustrating task and subsequent behavior problems in 225 2 1/2 year olds (129 Prenatally Cocaine and Other Drug Exposed [PCE], 30 Non Cocaine but other drug Exposed [NCE], 66 Non Drug Exposed [NDE]). Findings indicated a trend for PCE toddlers to show greater agitated emotional arousal than NCE and NDE toddlers. Further, PCE boys made more references to their caregivers in the task than NDE boys. Higher agitated arousal at age 2 1/2 years was related to greater decreases in externalizing behaviors through age 5 1/2 years. Findings suggest a link between cocaine exposure and emotional arousal and regulation and highlight the need to understand complex relations between emotion and risk for later psychopathology in exposed youth.

Chasnoff, I. (2001). The nature of nurture: Biology, environment, and the drug-exposed child. Chicago: National Training Institute Publishing.

The health consequences for children exposed to alcohol, cocaine, and other drugs are enormous, but the implications for behavior and learning are even greater. This book explores the biological and environmental factors that impact the ultimate development of drug-exposed children and presents practical strategies for helping children reach their full potential at home and in the classroom. In particular, this book addresses risk and protective factors in the life of a child; fetal alcohol syndrome; drugs, pregnancy, and the growing child; understanding children’s behavior; a theoretical basis for behavioral change; developing an intervention strategy; and the problem-solving process for behavior management.

Cleary, B. J., Donnelly, J., Strawbridge, J., Gallagher, P. J., Fahey, T., Clarke, M., & Murphy, D. J. (2010). Methadone dose and neonatal abstinence syndrome – systematic review and meta-analysis. Addiction, 105(1), pp. 2071-2084.

This article presents the findings of a study aimed at determining of there is a relationship between maternal methadone doses in pregnancy and the diagnosis or medical treatment of neonatal abstinence syndrome (NAS) using a review of the literature. According to the authors, severity of NAS does not appear to differ according to whether mothers are on high- or low-dose methadone maintenance therapy.

Creanga, A. A., Sabel, C. J., Ko, Y. J., Wasserman, R. C., Shapiro-Mendoza, K. C., Taylor, P., Barfield, W…Paulozzi, L. J. (2012). Maternal drug use and its effect on neonates: A population-based study in Washington State. The American College of Obstetricians and Gynecologists, 119(5), pp. 924-933.

The objective of this study was to estimate the effect of maternal illicit and prescription drug use on neonates in Washington State between 2000 and 2008. According to the authors, drug exposure and neonatal abstinence syndrome rates increased significantly between 2000 and 2008, neonatal abstinence syndrome rates being consistently higher than national figures. Maternal use of illicit and prescription drugs was associated with considerable neonatal morbidity and significantly higher rates of drug exposure and neonatal abstinence syndrome in recent years. Data suggest that opioid analgesics contributed to the increase in prenatal drug exposure and neonatal abstinence syndrome in Washington State. In accordance with current guidelines, our findings emphasize the need for clinicians to screen pregnant women for illicit and prescription drug use and minimize use of opioid analgesics during pregnancy.

Davies, J. K., & Bledsoe, J. M. (2005). Prenatal alcohol and drug exposures in adoption. Pediatric Clinics of North America, 52(5), pp. 1369-1393.

Families choosing to adopt domestically or internationally are faced with the possibility of prenatal substance exposure for their child. As more families turn to medical providers for consultation before adoption, the challenge of accurately identifying risk factors (such as prenatal substance exposure) for poor medical or cognitive outcomes becomes paramount. Although accurate data from the pregnancy history are crucial to helping medical professionals assess the risk of adverse neurodevelopmental outcomes in waiting children, these data are frequently not available at the time of a pre-adoptive medical review. Even with prenatal history available, it is extremely difficult to disentangle the consequences of prenatal substance exposure from the frequent comorbidities of prematurity, malnutrition, neglect, abuse, multiple placements, or institutional deprivation as discussed elsewhere in this issue. In addition, prenatal exposure to potentially harmful substances often occurs in the context of social dysfunction: poverty, parental addiction, impaired parenting, and poor access to services. A family history of mental illness or learning disabilities is often present, which can carry additional genetic risk for adoptees. This article addresses the major potential prenatal substance exposures for children joining families by adoption or, indeed, by birth: alcohol, opiates, tobacco, marijuana, cocaine, and methamphetamines. For each substance, the authors review the teratogenicity of the exposure and identify the spectrum of neurodevelopmental issues that can present in children exposed to this substance. Diagnosis of the spectrum of fetal alcohol outcomes is also discussed. When possible, the authors provide country-specific statistics on exposure risks for adopted children.

Day, N. L., Goldschmidt, L., & Thomas, C. A. (2006). Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14. Addiction, 101(9), pp. 1313-1322.

The purpose of this study was to evaluate the effects of prenatal marijuana exposure (PME) on the age of onset and frequency of marijuana use among 14-year-olds. In this longitudinal cohort study, women were recruited in their fourth prenatal month from a hospital-based prenatal clinic. Women and children were followed throughout pregnancy and at multiple time-points into adolescence. The women ranged in age from 18 to 42, half were African American and half Caucasian, and most were of lower socio-economic status. The women were generally light to moderate substance users during pregnancy and subsequently. At 14 years, 580 of the 763 offspring-mother pairs (76%) were assessed regarding socio-demographic, environmental, psychological, behavioral, biological and developmental factors. A total of 563 pairs (74%) were included in this analysis. Outcomes were age of onset and frequency of marijuana use at age 14. PME predicted age of onset and frequency of marijuana use among the 14-year-old offspring. This finding was significant after controlling for other variables including the child's current alcohol and tobacco use, pubertal stage, sexual activity, delinquency, peer drug use, family history of drug abuse and characteristics of the home environment including parental depression, current drug use and strictness/supervision. The authors conclude that prenatal exposure to marijuana, in addition to other factors, is a significant predictor of marijuana use at age 14.

De Cubas, M. M. (1984). Developmental outcome of children of methadone dependent women. ProQuest Dissertations and Theses.

The aim of this article is to provide a detailed report on research concerning children living in an environment in which drugs are used. The results indicate that children in the study born prenatally exposed presented with appropriate intellectual development but suggest difficulties in the emotional/behavioral domain.

Derauf, C., LaGasse, L. L., Smith, L. M ., Grant, P., Shah, R., Arria, A., Huestis, M….Lester, B. M. (2007). Demographic and psychosocial characteristics of mothers using methamphetamine during pregnancy: Preliminary results of the infant development, environment, and lifestyle study (IDEAL). The American Journal of Drug and Alcohol Abuse, 33(2), pp. 281.

This study describes the psychological characteristics and caretaking environments of 131 women enrolled in the first longitudinal study of prenatal methamphetamine (MA) exposure and child development. Prenatal MA use was associated with lower maternal perceptions on quality of life, greater likelihood of substance use among family and friends, increased risk for ongoing legal difficulties, and a markedly increased likelihood of developing a substance abuse disorder. Our preliminary findings suggest that MA using women are more likely to have multiple, intertwined psychosocial risks that may result in maladaptive parenting and caregiving. These factors may impact the developmental outcomes of affected children.

Effects of prenatal alcohol exposure on hippocampal volume, verbal learning, and verbal and spatial recall in late childhood. (2008). Journal of the International Neuropsychological Society, 14(6), pp. 1022-1033.

Children with prenatal alcohol exposure (PAE) show deficits in verbal learning and spatial memory, as well as abnormal hippocampal development. The relationship between their memory and neuroanatomic impairments, however, has not been directly explored. Given that the hippocampus is integral for the synthesis and retrieval of learned information and is particularly vulnerable to the teratogenic effects of alcohol, we assessed whether reduced learning and recall abilities in children with fetal alcohol spectrum disorders (FASDs) are associated with abnormal hippocampal volumes. Nineteen children with FASDs and 18 typically developing controls aged 9 to 15 years were assessed for verbal learning and verbal and spatial recall and underwent structural magnetic resonance imaging. Images were analyzed for total intracranial volume and for right and left hippocampal volumes. Results revealed smaller left hippocampi and poorer verbal learning and verbal and spatial recall performance in children with FASDs than controls, as well as positive correlations between selective memory indices and hippocampal volumes only in the FASD group. Additionally, hippocampal volumes increased significantly with age in controls only, suggesting that PAE may be associated with long-term abnormalities in hippocampal development that may contribute to impaired verbal learning and verbal and spatial recall.

Eiden, R. D., McAuliffe, S., Kachadourian, L., Coles, C., Colder, C., & Schuetze, P. (2009). Effects of prenatal cocaine exposure on infant reactivity and regulation. Neurotoxicology & Teratology, 31(1), pp. 60-68.

The purpose of this study was to examine the role of prenatal cocaine exposure and associated risk factors on infant reactivity and regulation at 7 months of infant age. Participants consisted of 167 mother–infant dyads participating in an ongoing longitudinal study of prenatal cocaine exposure, who completed the arm restraint procedure at the 7-month assessment (87 cocaine exposed, 80 non-cocaine exposed). The authors hypothesized that cocaine exposed infants would display higher arousal or reactivity and lower regulation during a procedure designed to arouse anger/frustration. Results indicated that cocaine exposed infants were more reactive to increases in the level of stress from trial 1 to trial 2 but exhibited no change in the number of regulatory strategies as stress increased, unlike the control group infants. Infant birth weight moderated the association between cocaine exposure and infant regulation. Among cocaine exposed infants, those with lower birth weight displayed higher reactivity compared to those with higher birth weight. Contrary to expectations, there were no indirect effects between cocaine exposure and infant reactivity/regulation via environmental risk, parenting, or birth weight. Results are supportive of a teratological model of prenatal cocaine exposure for infant reactivity/regulation in infancy.

Eiden, R. D., Granger, D. A., Schuetze, P., & Veira, Y. (2011). Child behavior problems among cocaine-exposed toddlers: Indirect and interactive effects. Development and Psychopathology, 23(2), pp. 539-550. DOI: 10.1017/S0954579411000058

This study examined the role of maternal psychopathology and maternal warmth as mediators of the association between prenatal cocaine and other substance exposure and toddler behaviour problems. It was also hypothesized that infant cortisol reactivity and environmental risk may moderate these associations. Participants were 220 caregiver–infant dyads (119 cocaine exposed, 101 not cocaine exposed; 49% boys). Mother–infant dyads were recruited at delivery with assessments at 4–8 weeks and 7, 13, and 18 months of child ages. Results yielded no direct associations between prenatal cocaine/other substance exposure and toddler behaviour problems, but significant indirect associations between prenatal cigarette/alcohol exposure and toddler behaviour problems at 18 months. With regard to moderation, results indicated an indirect association between prenatal cocaine exposure and toddler behaviour problems via lower maternal warmth for children with higher, but not lower, cortisol reactivity at 7 months. Results suggest potential pathways to toddler behaviour problems among children at high biological risk.

Finnegan, L. P., Kron, R. E., Connaughton, J. F., & Emich, J. P. (1975). Neonatal abstinence syndrome: assessment and management. Addictive Diseases an International Journal, 2(1), pp. 141-158.

This article reports on the experiences of doctors at Philadelphia General Hospital and their use of a clinically based scoring system that monitors the full spectrum of abstinence symptoms, and is used to regulate the therapeutic drug dosage level in the passively addicted infants. From January 1970 to June 1972, 121 passively addicted infants were admitted to the high risk nursery for close observation and management. The scoring method used in this study appeared to be successful.

Flak, A. L., Bertrand, J., Denny, C. H., Kesmodel, U. S., & Cogswell, M. E. (2014). The association of mild, moderate, and binge prenatal alcohol exposure and child neuropsychological outcomes: A meta-analysis. Alcoholism: Clinical and Experimental Research, 38(1), pp. 214-226.

This article evaluates the literature on the association between mild, moderate, and binge prenatal alcohol exposure and child neurodevelopment. The authors’ findings support previous findings suggesting the detrimental effects of prenatal binge drinking on child cognition. Prenatal alcohol exposure at levels less than daily drinking might be detrimentally associated with child behavior. The results of this review highlight the importance of abstaining from binge drinking during pregnancy and provide evidence that there is no known safe amount of alcohol to consume while pregnant.

Goins, M. (2010). Newborn Drug Withdrawal. Pediatrics for Parents, 26(7/8), pp. 3-4.

In today's world, those working in health care know that careful screening of pregnant women and good prenatal care result in healthier babies by identifying those who may have a difficult start. Knowing the mother was taking prescription or illicit drugs can be helpful in the baby's first days. Sometimes, though, the mother denies her drug use and the baby shows signs of problems, of drug withdrawal. Newborn drug withdrawal is known in the medical world as neonatal abstinence syndrome, or NAS. This is the physical process the baby goes through once not receiving a medication anymore. A baby going through withdrawal may have tense muscles, tremors, frequent sneezing/yawning/hiccups, sweaty and mottled skin, vomiting and loose stools, and may be very restless, often unable to stop crying frantically. There are two causes for NAS: mother's prenatal drug use and drugs prescribed to the baby once born, such as fentanyl for pain control.

Gray, T. R., Choo, R. E., Concheiro, M., Williams, E., Elko, A., Jansson, L. M., Jones, H. E., & Huestis, M. A. (2010). Prenatal methadone exposure, meconium biomarker concentrations and neonatal abstinence syndrome. Addiction, 105(12), pp. 2151.

Methadone is standard pharmacotherapy for opioid-dependent pregnant women, yet the relationship between maternal methadone dose and neonatal abstinence syndrome (NAS) severity is still unclear. This research evaluated whether quantification of fetal methadone and drug exposure via meconium would reflect maternal dose and predict neonatal outcomes. Forty-nine opioid-dependent pregnant women received 30-110mg methadone daily. Maternal methadone dose, infant birth parameters and NAS assessments were extracted from medical records. Thrice-weekly urine specimens were screened for opioids and cocaine with newborn meconium specimens quantified for methadone, opioid, cocaine and tobacco biomarkers. According to the findings, methadone and its metabolite 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) concentrations in meconium did not predict infant birth parameters or NAS severity. Prospective urine testing defined meconium drug detection windows for opiates and cocaine as 3 months, rather than the currently accepted 6 months. The presence of opioids in meconium could be used as a biomarker for infants at elevated risk in the newborn period.

Grim, K., Harrison, E. T., Wilder, T. R. (2012). Management of neonatal abstinence syndrome from opioids. Clinics in Perinatology, 40(3), pp. 509-524.

This article provides background on NAS, as well as treatment and management strategies. The constellation of behavioral and physiologic signs and symptoms include tremulousness, irritability, inconsolability, as well as feeding intolerance, emesis, watery stools, seizures, tachycardia, and respiratory distress. It has been suggested that affected neonates have an increased propensity for the development of attention-deficit/hyperactivity disorder as they mature.

Hamilton, G. (2012). Neonatal abstinence syndrome as consequence of prescription opioid use during pregnancy. International Journal of Childbirth Education, 27(3), pp. 69-72.

This article recreates a day in the life of a nurse/counselor who well knows the dilemmas faced by women who are depen¬dent on prescription opioids and discover they are pregnant. The article also focuses on the newborns and the decisions that must be made at the time of delivery, and provides treatment options for withdrawal of prescription drugs.

Hyter, Y. D. (2007). Understanding children who have been affected by maltreatment and prenatal alcohol exposure. Language Speech and Hearing Services in Schools, 38(2), pp. 93-98.

This prologue introduces an important topic for multiple disciplines involved with children and their families. This introduction includes a review of some of the current literature on the effects of maltreatment and prenatal alcohol exposure on child development, an explanation of why this topic is essential learning for communication professionals, prevalence figures for the occurrence of these effects, and a summarization of the articles that have been contributed by a cross section of researchers from various disciplines.

Hudak, M. L., & Tan, R. C. (2012). Clinical report: neonatal drug withdrawal. American Academy of Pediatrics, 129(2), pp. e540-e560. DOI: 10.1542/peds.2011-3212

This statement updates information about the clinical presentation of infants exposed to intrauterine drugs and the therapeutic options for treatment of withdrawal and is expanded to include evidence-based approaches to the management of the hospitalized infant who requires weaning from analgesics or sedatives.

Jansson, L. M., Di Pietro, J. A., Elko, A., Williams, E. L., Milio, L., Velez, M. (2012). Pregnancies exposed to methadone, methadone and other illicit substances, and poly-drugs without methadone: A comparison of fetal neurobehaviors and infant outcomes. Drug and Alcohol Dependence, 122(1), pp. 213-219.

This article presents findings of a study comparing infants exposed to methadone and other illicit drugs with two control groups (methadone only and no drug exposure), focusing on neurobehavioral development and infant outcomes. Results of the study show that poly-drug exposure may potentiate the effects of methadone on the fetus and infant and highlight the need for intensive treatment for methadone-maintained women who abuse other substances.

Jones, H. E., Fischer, G., Heil, S., Kaltenbach, K., Martin, P. R., Coyle, M. G., Selby, P... Arria, A. M. (2014). Maternal opioid treatment: human experimental research (MOTHER) – approach, issues and lessons learned. Addiction, 107(Supplement 1), pp. 28-35.

This article presents the findings of the MOTHER study, aimed at investigating the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. The authors present seven important lessons learned from the study.

Jones, H. E., Dengler, E., Garrison, A., O’Grady, K. E., Seashore, C., Horton, E., Andringa, K., Janson, L. M., & Thorp, J. (2014). Neonatal outcomes and their relationship to maternal buprenorphine dose during pregnancy. Drug and Alcohol Dependence, 134(1), pp. 414-417.

This article aims to look at (1) examined the relationship between maternal buprenorphine dose at delivery and neonatal abstinence syndrome (NAS) peak score, estimated gestational age at delivery, Apgar scores at 1 and 5 min, neonatal head circumference, length, and weight at birth, amount of morphine needed to treat NAS, duration of NAS treatment, and duration of neonatal hospital stay and (2) compared neonates who required pharmacotherapy for NAS to neonates who did not require such pharmacotherapy on these same outcomes. Findings failed to support the existence of a dose-response relationship between maternal buprenorphine dose at delivery and any of 10 neonatal clinical outcomes, including NAS severity and (2) that infants treated for NAS had a higher mean NAS peak score and, spent a longer time in the hospital than did the group not treated for NAS is unsurprising.

Kaltenbach, K., Holbrook, M. A., Coyle, G. M., Heil, H. S., Salisbury, L. A., Stine, M. S., Martin, R. P., & Jones, E. H. (2012). Predicting treatment for neonatal abstinence syndrome in infants born to women maintained on opioid agonist medication. Addiction, 107, pp. 45-52. DOI: 10.1111/j.1360-0443.2012.04038.x

The authors of this study tried to identify factors that predict the expression of neonatal abstinence syndrome (NAS) in infants exposed to methadone or buprenorphine in utero. According to the results, maternal weight at delivery, estimated gestational age, infant birth weight, delivery type, maternal nicotine use and days of maternal study medication received and the use of psychotropic medications in pregnancy may play a role in the expression of neonatal abstinence syndrome severity in infants exposed to either methadone or buprenorphine.

Kocherlakota, P. (2014). Neonatal abstinence syndrome. Pediatrics, 134(2), pp. e547-e561. DOI: 10.1542/peds.2013-3524

This article provides a brief explanation of what neonatal abstinence syndrome (NAS) is, historical background, incidence rates, clinical presentation of NAS, and management of NAS including non-pharmacological and pharmacological care. This is a great resource for direct practitioners to educate themselves on how to identify and treat babies presenting with NAS upon birth.

Kraft, K. W., & Van den Anker, N. J. (2012). Pharmacologic management of the opioid neonatal abstinence syndrome. Pediatric Clinics of North America, 59(5), pp. 1147-1165.

Neonatal withdrawal symptoms have been noted following prenatal exposure to several drugs. Examples include opioids,1,2 benzodiazepines,3,4 mood-stabilizing medications, 5 selective serotonin reuptake inhibitors,6 and nicotine.7 For all drug classes except opioids, these symptoms are usually self-limited and do not require pharmacologic treatment. Infants born to mothers with opioid abuse or receiving methadone maintenance often develop withdrawal symptoms, following the postpartum cessation of in utero exposure to opioids. This complex is known as the neonatal abstinence syndrome (NAS). The full mechanistic basis for the clinical presentation is unclear. Tolerance induced by long-term exposure to opioids is primarily mediated by receptor down regulation coupled with up regulation in the cyclic adenosine monophosphate (cAMP) pathway.

Lambert, B. L., Bauer, C. R. (2012). Developmental and behavior consequences of prenatal cocaine exposure: a review. Journal of Perinatology, (61) Supplement 1, pp. 819-828.

This article reviews the most recent literature regarding the association between in utero cocaine exposure and developmental and behavioral outcomes from birth through adolescence across various domains of functioning (growth, neurobiology, intelligence, academic achievement, language, executive functioning, behavioral regulation and psychopathology). Given the large number of exposed children in the child welfare system and the increased need for medical, mental health and special education services within this population, more definitively documenting associations between prenatal cocaine exposure and later child outcomes is essential in order to be able to prospectively address the many significant public health, economic and public policy implications.

Lemola, S., Stadlmayr, W., & Grob, A. (2009). Infant irritability: The impact of fetal alcohol exposure, maternal depressive symptoms, and low emotional support from the husband. Infant Mental Health Journal, 30(1), pp. 57-81.

The aim of this study was to investigate the impact of fetal alcohol exposure, maternal depressive symptoms, and low emotional support from the husband on infant irritability in the first one and a half years of life. Four models describing the interplay of these factors were assessed: A direct effect model, an interaction or threshold model, a mediational model and a transactional model. Method: A sample of initially 458 women was assessed in a prospective 3-wave study across the first 17 months after childbirth. Fetal alcohol exposure was questioned retrospectively six weeks after birth. Infant irritability was reported by the mothers and fathers. Direct effects of fetal alcohol exposure, maternal depressive symptoms, and low emotional support from the husband on infant irritability as well as an interaction between fetal alcohol exposure and maternal depressive symptoms were revealed. The interaction can be understood in terms of a diathesis-stress model. However, no longitudinal associations between maternal depressive symptoms and infant irritability could be found.

Lester, B. M., Bagner, D. M., Liu, J., LaGasse, L. L., Seifer, R., Bauer, C. R., Shankaran, S...Das, A. (2009). Infant neurobehavioral dysregulation: Behavior problems in children with prenatal substance exposure. Pediatrics, 124(5), pp. 1355-1362. DOI: 10.1542/peds.2008-2898

The objective of this study was to test a developmental model of neurobehavioral dysregulation relating prenatal substance exposure to behavior problems at age 7. The sample included 360 cocaine-exposed and 480 unexposed children from lower to lower middle class families of which 78% were black. Structural equation modeling was used to test models whereby prenatal exposure to cocaine and other substances would result in neurobehavioral dysregulation in infancy, which would predict externalizing and internalizing behavior problems in early childhood. The paths in the models indicate that there are direct effects of prenatal substance exposure on 7-year behavior problems as well as indirect effects, including neurobehavioral dysregulation. The findings suggest that prenatal substance exposure affects behavior problems at age 7 through 2 mechanisms. The direct pathway is consistent with a teratogenic effect. Indirect pathways suggest cascading effects whereby prenatal substance exposure results in neurobehavioral dysregulation manifesting as deviations in later behavioral expression. Developmental models provide an understanding of pathways that describe how prenatal substance exposure affects child outcome and have significant implications for early identification and prevention.

Lester, M. B., Lin, H., DeGarmo, S. D., Fisherd, A. P., LaGassea, L. L., Levine, P. T., Shankaran, S…Higginsk, D. R. (2012). Neurobehavioral disinhibition predicts initiation of substance use in children with prenatal cocaine exposure. Drug and Alcohol Dependence, 126, pp. 80-86.

Through this study, the authors aim to determine if there is an association between these Neurobehavioral Disinhibition scores and initiation of substance use between ages 8 and 16. Our hypothesis was that prenatal cocaine exposure predisposes the child to ND, which, in turn, is associated with initiation of substance use by age 16. The results show that prenatal drug exposure appears to be a risk pathway to ND, which by 8/9 years portends substance use initiation.

Lewis, B. A., Minnes, S., Short, E.J., Weishampel, P., Satayathum, S., Min, M., Nelson, S., & Singer, L. T. (2011). The effects of prenatal cocaine on language development at 10 years of age. Neurotoxicology and Teratology, 33(1), pp. 17-24.

To examine the long term effects of prenatal cocaine exposure (PCE) on the language development of 10-year-old children utilizing a prospective design, controlling for confounding drug and environmental factors. Children exposed to cocaine in utero (PCE; n = 175) and non-exposed children (NCE; n = 175) were followed prospectively to 10 years of age and were compared on language subscales of the Test of Language Development-Intermediate 3rd Edition (TOLD-I: 3) and phonological processing as measured by the Comprehensive Test of Phonological Processing (CTOPP). According to the findings, the caregiver factors of vocabulary, HOME, and psychological symptoms also had consistent effects on language subtests and phonological processing scores. Children with PCE who experienced foster or adoptive care had enhanced language development compared to those living with birth mothers or in relative care. Cocaine exposed girls had lower scores on the phonological awareness subscale of the CTOPP than non-exposed girls. PCE has subtle effects on specific aspects of language development and phonological processing at age 10, even after controlling for confounding variables. Environmental factors (i.e., postnatal lead exposure, home environment, and caregiver vocabulary and psychological symptoms) also impact language skills at 10 years. Adoptive or foster care appears to enrich PCE children's linguistic environment and protects children against language delay in the PCE sample.

Logan, B. A., Brown, M. S., Hayes, M. J. (2013). Neonatal abstinence syndrome: treatment and pediatric outcomes. Clinical Obstetrics and Gynecology, 56(1), pp. 186-192.

This article presents short-term and long-term developmental outcomes associated with prenatal opiate exposure, including symptoms and severity of NAS and early cognitive and motor delays. The authors discuss maternal and infant risk factors including patterns of maternal substance use during pregnancy, genetic risk, polysubstance exposure pharmacological treatment for NAS and breastfeeding.

Mactier, H. (2013). Neonatal and longer term management following substance misuse in pregnancy. Early Human Development, 89(11), pp. 887-892.

This article is a review of the current literature on NAS and considers current evidence and discusses best practice in the neonatal management and follow-up of affected babies. Authors state that more studies are required to explore alternatives to methadone maintenance in pregnancy and to define optimal treatment for neonatal abstinence syndrome. All infants born to drug-misusing mothers must be considered vulnerable, even if they have not required treatment for neonatal abstinence syndrome.

Mactier, H., Shipton, D., Dryden, C., & Tappin, D. M. (2014). Reduced fetal growth in methadone-maintained pregnancies is not fully explained by smoking or socio-economic deprivation. Addiction, 109(3), pp. 482-488. DOI: 10.1111/add.12400

The aim of this article is to determine if reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is explained by cigarette smoking or socio-economic deprivation. This study shows that reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is not fully explained by cigarette smoking, area deprivation, maternal age or parity.

Minnes, S., Singer, L. T., Humphrey-Wall, R., & Satayathum, S. (2008). Psychosocial and behavioral factors related to the post-partum placements of infants born to cocaine-using women. Child Abuse & Neglect, 32(3), pp. 353-366.

One of the objectives of this study was to determine if cocaine-using women who did not maintain infant custody (NMC) would report more psychological distress, domestic violence, negative coping skills, lower social support and more childhood trauma than cocaine-using women who maintained custody (MC) of their infant. A second objective was to evaluate the relative contribution of psychosocial factors to infant placement. Psychosocial profiles of MC women (n = 144) were compared with NMC (n = 66) cocaine-using women. Subjects were low income, urban, African-American women who delivered an infant at a county teaching hospital. The NMC group reported greater overall psychological distress, psychoticism, somatization, anxiety and hostility than the MC group. Findings suggest that the NMC women have more negative psychological and behavioral functioning post-partum than MC women. Less prenatal care and greater cocaine use, psychological distress and maternal childhood emotional neglect are associated with the post-partum placement of infants born to cocaine-using women. Results of this study indicate that poor, urban women who use cocaine prenatally display several measurable differences on psychosocial and behavioral risk factors based on child placement status. Among these risk factors heavier cocaine use, lack of prenatal care, more severe psychological symptoms and early childhood experiences of emotional neglect increase the likelihood of loss of infant custody. Routine, objective assessments of psychosocial and behavioral characteristics of women who use cocaine during pregnancy can aid Child Protective Service workers and clinicians by providing baseline data from which to tailor interventions and set improvement criteria for mother-child reunification.

Minnes, S., Singer, L. T., Min, M. O., Lang, A. M., Ben-Harush, A., Short, E., & Wu, M. (2014). Comparison of 12-year-old children with prenatal exposure to cocaine and non-exposed controls on caregiver ratings of executive function. Journal of Youth and Adolescence, 43, pp. 53-69. DOI: 10.1007/s10964-013-9927-3

This article looks at differences in caregiver reported executive function in 12-year-old children who were prenatally exposed to cocaine (PCE) compared to children who were not prenatally exposed. Higher current caregiver psychological distress levels were independently associated with poorer ratings on executive function scales. Assessment and targeted interventions to improve metacognitive processes are recommended for girls who were prenatally exposed to cocaine.

Minnes, S., Singer, L., Min, M.O., Wu, M., Lang, A., & Yoon, S. (2014). Effects of prenatal cocaine/poly-drug exposure on substance use by age 15. Drug and Alcohol Dependence, 134 (1), pp. 201-210.

This study examined effects of prenatal cocaine exposure (PCE) on tobacco, alcohol, marijuana and cocaine use by age 15. Results of the study reflects percentages of drug use as follows: tobacco 35% vs. 26%; marijuana 33% vs. 23%; alcohol 40% vs. 35%; and any drugs 59% vs. 50%. PCE adolescents were twice as likely to use tobacco, 2.2 times more likely to use alcohol; and 1.8 times more likely to use marijuana than NCE adolescents. Results also reflected that PCE non-African American adolescents had greater probability of tobacco use (65%) than NCE non-African American youth (21%). PCE was associated with any drug use while higher BLL predicted alcohol use. Violence exposure was a predictor of tobacco, marijuana and any drug. PCE and exposure to violence increased the likelihood of tobacco, marijuana or any drug use by age 15, while PCE and higher early BLL predicted alcohol use. Prevention efforts should target high risk groups prior to substance use initiation.

Murphy-Oikonen, J., Montelpare, J. W., Bertoldo, L., Southon, S., & Persichino, N. (2012). The impact of a clinical practice guideline on infants with neonatal abstinence syndrome. British Journal of Midwifery, 20(7), pp. 493-501.

This study evaluated the effectiveness of clinical practice guideline (CPG) on increasing identification of neonates with neonatal abstinence syndrome (NAS) symptoms based on a toxicology screening protocol, decreasing the mean NAS score for neonates and, decreasing the average length of hospital admission, based on standardized treatment and weaning protocol of morphine or phenobarbital. A high proportion of neonates born to opiate-using pregnant women develop the withdrawal condition known as NAS. This study was successful in describing the benefit of implementing new CPG for managing neonates identified with NAS, and mothers suspected of using substances during their pregnancy.

Narkowicz, S., Plotka, J., Polkowska, Z., Biziuk, M., & Namiesnik, J. (2013). Prenatal exposure to substance of abuse: a worldwide problem. Environment International, 54(1), pp. 141-163.

This article presents general information on prenatal exposure to substances. It provides a brief introduction on maternal effects, and effects of substances in utero, effects on pregnancy and delivery, effects on the fetus, the newborn and the developing child, metabolism of the substances, and why it is important to use biological samples for the assessment of in utero exposure.

Nordstrom Bailey, B., Sood, B. G., Sokol, R. J., Ager, J., Janisse, J., Hannigan, J. H., Covington, C., & Delaney-Black, V. (2005). Gender and alcohol moderate prenatal cocaine effects on teacher-report of child behavior. Neurotoxicology & Teratology, 27(2), pp. 181-190.

The purpose of the current study was to determine the degree to which gender-specific effects of prenatal cocaine exposure on teacher-reported child externalizing behavior problems were evident when evaluated in relation to prenatal alcohol exposure. Subjects were single birth infants of mothers who were prospectively evaluated during pregnancy. At age seven, 499 children (214 exposed prenatally to cocaine) were evaluated in our laboratory and teacher reports were solicited. Results revealed that among boys with prenatal alcohol exposure, co-occurring prenatal cocaine exposure was associated with increased levels of teacher reported externalizing behavior, particularly delinquent behavior. Boys with any prenatal cocaine exposure were twice as likely as unexposed boys to have clinically significant externalizing behavior scores. For girls, prenatal cocaine exposure only was associated with increased levels of externalizing behaviors and aggressive behavior. The current findings support gender- and alcohol-moderated effects of prenatal cocaine exposure on school-age teacher-reported child behavior problems. These findings are consistent with other studies that have suggested that behavior of boys is more likely to be negatively impacted by prenatal and postnatal environmental influences than the behavior of girls.

Ondersma, J. S., Winhusen, T. & Lewis, F. D. (2012). Pre-treatment change in a randomized trial with pregnant substance-abusing women in community-based outpatient treatment. Contemporary Clinical Trials, 33(5), pp. 1074–1079 DOI: 10.1016/j.cct.2012.06.002

This article summarizes the results of a study which evaluated a) the presence of pre-treatment change; b) the extent to which that change, if any could be specifically associated with a baseline assessment and randomization session; and c) the specificity of any observed change in pregnant woman from a clinical trial. The results of the study reflect that change was sudden and non-linear. The authors suggest that change may be the result of a series of interactions between external efforts (i.e. brief intervention), personal characteristics, substance use severity, state variables, recency and salience of use-related negative consequences or pro-change messages.

Patrick, S. W., Kaplan, H. C., Passarella, M., Davis, M. M., & Lorch, S. A. (2014). Variation in treatment of neonatal abstinence syndrome in U.S. Children’s Hospitals, 2004-2011. Journal of Perinatology, 34(1), pp. 867-872.

The objective of this study was to determine whether different pharmacotherapies for NAS are associated with differences in outcomes and to determine whether pharmacotherapy and outcome vary by hospital. The findings of the study suggest that there is variation in hospital treatment for NAS among major US children’s hospitals, findings also reflect that methadone as the initial treatment was associated with reduced length of treatment and hospital stay.

Popoval, S., Stade, B., Bekmuradov, D., Lange, S., & Rehm, J. (2011). What do we know about the economic impact of fetal alcohol spectrum disorder? A systematic literature review. Alcohol and Alcoholism, 46(4), pp. 490-497. DOI: 10.1093/alcalc/agr029

The objective of this study was to conduct a systematic review of the literature related to the measurement of the economic impact of Fetal Alcohol Spectrum Disorder (FASD) in different countries and to categorize the available literature. There are a limited number of studies found in Canada and the USA, and data from the rest of the world are absent. Existing estimates of the economic impact of FASD demonstrate significant cost implications on the individual, the family and society. However, these estimates vary considerably due to the different methodologies used by different studies. Limitations and gaps in the existing methodologies of calculating the economic costs of FASD are discussed. It is evident that there is an urgent need to develop a comprehensive and sound methodology for calculating the economic impact of FASD to the society.

Pritham, A. U., Paul, A. J., & Hayes, J. M. (2012). Opioid dependency in pregnancy and length of stay for neonatal abstinence syndrome. Journal of Obstetric, Gynecologic, & Neonatal Nursing, 41(2), pp. 180-190. DOI: 10.1111/j.1552-6909.2011.01330.x

This study examines opioid replacement therapy in pregnancy and effect on neonatal outcomes, including length of hospital stay for neonatal abstinence syndrome. The findings of this study suggest that the simultaneous use of methadone and benzodiazepines during pregnancy provide further direction for the treatment of opioid dependency during pregnancy. Harm reduction strategies for opioid-dependent pregnant women in substance abuse treatment with MMT may one day include guidance on daily treatment doses and recommendations to avoid the concomitant use of benzodiazepines to lessen NAS. Breastfeeding should be recommended to shorten length of stay.

Richardson, G. A., Larkby, C., Goldschmidt, L., & Day, N. L. (2013). Adolescent initiation of drug use: effects of prenatal cocaine exposure. Journal of the American Academy of Child & Adolescent Psychiatry, 52(1), pp. 37-46.

This study seeks to investigate the direct effects of prenatal cocaine exposure (PCE) on adolescent drug use, while controlling for other predictors of adolescent use. First trimester cocaine exposure significantly predicted earlier adolescent marijuana and alcohol initiation. The hazard of marijuana and alcohol initiation among exposed adolescents was almost two times greater than among non-exposed adolescents, adjusting for other significant factors. There were no differences in tobacco initiation. Other significant predictors of adolescent drug use were family history of alcohol problems, exposure to violence, and childhood maltreatment. Cocaine exposure during early pregnancy was associated with initiation of marijuana and alcohol use. Exposure to violence, childhood maltreatment, and familial factors also predicted adolescent initiation, but did not mitigate the effects of PCE. The combination of these risk factors has significant implications for the development of later substance use, social, and psychiatric problems.

Riley, E. P., & McGee, C. L. (2005). Fetal alcohol spectrum disorders: An overview with emphasis on changes in brain and behavior. Experimental Biology and Medicine, 230(6), pp. 357-365.

Fetal alcohol spectrum disorders constitute a major public health problem. This article presents an overview of important issues that surround these disorders and emphasizes the structural and neurobehavioral consequences associated with prenatal exposure to alcohol. Diagnostic criteria are discussed, and possible moderating factors for the range of outcomes are mentioned. In addition, the prevalence of fetal alcohol spectrum disorders is described, and estimates of the financial impact of these disorders are given. A wide range of neuropsychological deficits have been found in children prenatally exposed to alcohol, including deficits in visuospatial functioning, verbal and nonverbal learning, attention, and executive functioning. These children also exhibit a variety of behavioral problems that can further affect their daily functioning. Children exposed to alcohol prenatally, with and without the physical features of fetal alcohol syndrome, display qualitatively similar deficits.

Sarkola, T., Gissler, M., Kahila, H., Autti-Ramo, I. & Halmesmaki, E. (2012). Alcohol and substance abuse identified during pregnancy: maternal morbidity, child morbidity and welfare interventions. Acta Pediatrica, 101(7), pp. 784-790.

The authors look at the relations between postnatal maternal morbidity, child morbidity and welfare interventions in families with prenatal alcohol or substance abuse. Postnatal maternal abuse-related healthcare utilization and use of medication were associated with child out-of-home care. Significant differences were observed in the categories of maternal mental and behavioral disorders caused by psychoactive substance use as well as injury and poisoning. Maternal inpatient care for mental and behavioral disorders peaked at the time of child out-of-home care. Maternal abuse related healthcare utilization was associated with early child healthcare utilization and use of medication for mental and behavioral disorders. These associations were largely explained by the association with child out-of-home care. The authors suggest that postnatal maternal abuse-related morbidity is associated with significant early child morbidity, use of medication and timing of out-of-home care.

Schiller, C., & Allen, P.J. (2005). Follow-up of infants prenatally exposed to cocaine. Pediatric Nursing, 31(5), pp. 427-436.

Maternal cocaine use during pregnancy continues to be of great concern for health care professionals. Research in this area has increased as investigators examine the effects of prenatal cocaine exposure in the infant/young child. This paper reviews the literature, identifies the primary care needs of infants and young children with a known history of prenatal cocaine exposure, and presents guidelines for the primary care practitioner to monitor the infant's physiologic and developmental sequelae during the first 3 years of life. Findings in the literature demonstrate inconsistencies in regard to the physiologic and developmental outcomes of infants/young children prenatally exposed to cocaine. The authors conclude that further research is warranted, as it is evident from studies that not all investigators are controlling for confounding variables such as poly-drug use, which is necessary in isolating cocaine's effects.

Serane, V. T., & Kurian, O. (2012). Neonatal abstinence syndrome. Indian Journal of Pediatrics, 75(9), pp. 911-914.

This is a case note review of the population affected by Neonatal Abstinence Syndrome. Infants of mothers who had taken substance of misuse were monitored regularly using Finnegan’s score and treatment initiated based on a pre-existing protocol. The parameters that were studied included maternal drug habits, antenatal problems, and neonatal epidemiology with particular reference to growth, Neonatal Abstinence Syndrome (NAS), its severity and management. According to the study, the dose of methadone taken by the mother related well with the likelihood of development of NAS. The most common symptoms noted at the time of diagnosis were irritable cry, increased tone, tachypnea, sleeplessness and tremor. Majority of neonates born to mothers on methadone exhibit neonatal abstinence syndrome and require pharmacological treatment. Neonates who had not exhibited symptoms of drug withdrawal within the first 3 days of life are unlikely to present with NAS requiring treatment.

Shankaran, S., Lester, B. M., Das, A., Bauer, C. R., Bada, H.S., Lagasse, L., & Higgins, R. (2007). Impact of maternal substance use during pregnancy on childhood outcome. Seminars in Fetal Neonatal Medicine, 12(2), pp. 143-150.

The impact of maternal substance abuse is reflected in the 2002-2003 National Survey on Drug Use and Health. Among pregnant women in the 15-44 age group, 4.3%, 18% and 9.8% used illicit drugs, tobacco and alcohol, respectively. Maternal pregnancy complications following substance use include increases in sexually transmitted disorders, placental abruption and HIV-positive status. Effects on the neonate include a decrease in growth parameters and increases in central nervous system and autonomic nervous system signs and in referrals to child protective agencies. In childhood, behavioral and cognitive effects are seen after prenatal cocaine exposure; tobacco and alcohol have separate and specific effects. The ongoing use of alcohol and tobacco by the caretaker affects childhood behavior. Therefore, efforts should be made to prevent and treat behavioral problems as well as to limit the onset of drug use by adolescent children born to women who use drugs during pregnancy.

Slamberova, R. (2012). drugs in pregnancy: the effects on mother and her progeny. Physiological Research, 61 Supplement 1, pp. S123-35.

This article reviews and summarizes the clinical and experimental evidence showing how opioids and psychostimulants can affect maternal behavior of drug-abusing mother and the development of their offspring. Authors conclude that the adverse effects of prenatal drug exposure are partially reversible by postnatal care, however preventive care is still the best “therapy.”

Smith, L. M., LaGasse, L. L., Derauf, C., Grant, P., Shah, R., Arria, A., et al. (2006). The infant development, environment, and lifestyle study: effects of prenatal methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth. Pediatrics, 118(3), pp. 1149-1156.

Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. This study examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development, Environment and Lifestyle (IDEAL) study. The IDEAL study screened 13 808 subjects at 4 clinical centers: 1618 were eligible and consented, among which 84 were methamphetamine exposed, and 1534 were unexposed. The authors found that the methamphetamine exposed group was 3.5 times more likely to be small for gestational age than the unexposed group. Mothers who used tobacco during pregnancy were nearly 2 times more likely to have small-for-gestational-age infants. In addition, less maternal weight gain during pregnancy was more likely to result in a small-for-gestational-age infant. Birth weight in the methamphetamine exposed group was lower than the unexposed group. These findings suggest that prenatal methamphetamine use is associated with fetal growth restriction after adjusting for covariates. Continued follow-up will determine if these infants are at increased risk for growth abnormalities in the future.

Sood, B. G., Nordstrom Bailey, B., Covington, C., Sokol, R. J., Ager, J., Janisse, J., Hannigan, J. H., & Delaney-Black, V. (2005). Gender and alcohol moderate caregiver reported child behavior after prenatal cocaine. Neurotoxicology & Teratology, 27(2), pp. 191-201.

This study evaluates the effects of prenatal cocaine exposure on child behavior in a sample of 506 mothers and their children. Maternal alcohol, cigarette, and illicit drug use were assessed pre- and postnatally. Caregiver report of child behavior was assessed with the Achenbach Child Behavior Checklist. The authors found girls prenatal exposed to cocaine only had higher rates of adverse behavioral outcomes on caregiver reported child behaviors, such as externalizing (i.e., aggression), internalizing, and attention problems. No differences were found for boys prenatally exposed to cocaine only. Girls and boys with both prenatal cocaine and alcohol exposure had higher scores on delinquent behavior. Maternal age, cigarette and alcohol exposure during pregnancy, and current drug use were increased with prenatal cocaine exposure. In addition, children with any prenatal cocaine exposure were less likely to have consistently been in the custody of their biologic mother. These results emphasize the need for collection of longitudinal data to follow the effects of prenatal exposure in children. The manifestations of prenatal cocaine exposure are likely to change with the development of the child and are probably different in adolescents.

Sublett, J. (2013). Neonatal abstinence syndrome: Therapeutic interventions. MCN, March/April 2013. pp. 102-107.

This article provides an overview of the possible risks, benefits, and outcomes of pharmacologic and complementary therapies in the neonatal population, and illustrates the gaps in knowledge related to their use for neonatal withdrawal. It reviews guidelines for treatment, monitoring Neonatal Abstinence Syndrome (NAS), Pharmacologic Therapy, Nonpharmacologic Therapy, and Complimentary Alternative Medicine (CAM).

Soyka, M. (2013). Buprenorphine use in pregnant opioid users: A critical review. CNS Drugs, 27(8), pp. 653-662. DOI: 10.1007/s40263-013-0072-z

This article is a review of the literature on buprenorphine use in pregnancy. It discusses the most recent data which the author believes may facilitate clinical decisions on buprenorphine use for this group of women. According to the review of the literature, findings suggest that buprenorphine produces maternal outcomes similar to those associated with methadone. However neonates exposed to buprenorphine in utero who were treated for NAS required on average shorter treatment and less medication than those exposed to methadone. Findings also suggest that transferring pregnant women from methadone to buprenorphine can put the fetus at risk. These novel findings indicate that buprenorphine is emerging as a first-line treatment for pregnant opioid users.

Thomas, J. D., Warren, K. R., & Hewitt, B. G. (2010). Fetal alcohol spectrum disorders: From research to policy. Alcohol Research and Health, 33(1/2), pp. 118-126.

Research supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has contributed to the identification of the range and prevalence of fetal alcohol spectrum disorders (FASD), as well as methods for prevention and treatment of FASD. The worldwide prevalence and high personal and societal costs of FASD speak to the importance of this research. This article briefly examines some of the ways that NIAAA has contributed to our understanding of FASD, the challenges that we still face, and how this research is translated into changes in public policy.

Unger, A., Metz, V., & Fischer, G. (2012). Review article: Opioid dependent and pregnant: what are the best options for mothers and neonates? Obstetrics and Gynecology International, 2012, pp. 1- 6. DOI: 10.1155/2012/195954

This article seeks to provide an update to health professionals on the latest treatment approaches for mothers suffering from opioid dependence and their neonates. The article provides brief background on opioid dependence statistics, medical treatment of opioid-dependent pregnant women, perinatal pain management, NAS, predisposition to NAS and breastfeeding.

Vassoler, F. M., Byrnes, E. M., & Pierce, R. C. (2014). The impact of exposure to addictive drugs on future generations: Physiological and behavioral effects. Neuropharmacology, 76(1), pp. 269-275.

The goal of this review is to describe the trans-generational consequences of preconception exposure to drugs of abuse for five major classes of drugs: alcohol, nicotine, marijuana, opioids, and cocaine. The findings by the authors suggest that exposure to drugs produce transmissible epigenetic changes that result in alterations to the physiology and behavior of offspring.

Winklbaur, B., Kopf, N., Ebner, N., Jung, E., Thau, K., & Fischer, G. (2008). Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: a knowledge synthesis for better treatment for women and neonates. Addiction, 103(1), pp. 1429-1440. DOI: 10.1111/j.1360-0443.2008.02283.x

In this article, the authors review the literature on opioid dependence among pregnant women and provide recommendations as guidance in the management of treatment. The authors suggest that because women enter prenatal care at different stages in their pregnancy and from various settings, treatment services should be provided in a culturally sensitive and non-judgmental environment by the whole health-care personnel spectrum.

Whitaker, T. M., Bada, H. S., Bann, C. M., Shankaran, S., LaGasse, L., Lester, B. M., Bauer, C. R., Hammond, J., & Higgins, R. (2011). Serial pediatric symptom checklist screening in children with prenatal drug exposure. Journal of Development & Behavioral Pediatrics, 32(3), pp. 206-215. DOI: 10.1097/DBP.0b013e318208ee3c

The objective of this study was to examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure. The Maternal Lifestyle Study enrolled children with prenatal cocaine exposure (PCE) at birth for longitudinal assessments of developmental, behavioral, and health outcomes. At 8, 9, 10, 11, and 12 years of age, caregivers rated participants on the Pediatric Symptom Checklist (PSC). Serial PSC results were compared with an established broad-based behavioral measure at 9, 11, and 13 years. PSC results were analyzed for 1081 children who had at least 2 annual screens during the 5-year time span. Most subjects (87%) had 4 or more annual screens rated by the same caregiver (80%). PSC scores (and Positive screens) over time were compared at different time points for those with and without PCE. Covariates, including demographic factors and exposures to certain other substances, were controlled. Children with PCE had significantly higher scores overall, with more Positive screens for behavior problems than children without PCE. Children with PCE had more externalizing behavior problems. Children exposed to tobacco prenatally and postnatally also showed higher PSC scores. Over time, PSC scores differed slightly from the 8-year scores, without clear directional trend. Earlier PSC results predicted later behavioral outcomes. Findings of increased total PSC scores and Positive PSC screens for behavioral concerns in this group of children with prenatal substance exposure support the growing body of evidence that additional attention to identification of mental health problems may be warranted in this high-risk group.

Wobie, K., Eyler, F. D., Garvan, G. W., Hou, W., & Behnke, M. (2004). Prenatal cocaine exposure: An examination of out-of-home placement during the first year of life. Journal of Drug Issues, 34(1), pp. 77-94.

This paper presents basic placement issues for infants at risk for out-of-home placement by describing the postnatal living arrangements of a group of cocaine-exposed infants and a matched control group of non-exposed infants during their first year of life. Risk factors for infant placement outside of the maternal home are identified. Of this predominantly African-American, low socioeconomic status, multiparous cohort, 46% of the women who used cocaine prenatally had infants in out-of-home placement at some time during the first year of life. More positive life experiences and higher education significantly improved the potential of retaining custody. The prenatal and post-partum period is an important time to provide services that encourage substance abuse recovery and associated factors of stability that facilitate an intact mother-infant dyad. This study reinforces the idea that the pregnancy and postpartum period presents an opportunity for physicians and other medical practitioners to engage in more extensive interviewing of at-risk patients in order to identify and refer users as early as possible to substance abuse treatments and services.

Zabaneh, R., Smith, L. M., LaGasse, L. L., Defauf, C., Newman, E., Shah, R., Arria, A…Lester, B. M. (2012). The effects of prenatal methamphetamine exposure on childhood growth patterns from birth to 3 years of age. American Journal of Perinatology, 29(3), pp. 203-210.

This study examined the effects of prenatal methamphetamine (MA) exposure on growth parameters from birth to age 3 years. Results of the study suggest that children exposed prenatally to MA have a modest decrease in height growth trajectory during the first 3 years of life with no observed difference in weight, head circumference, or weight-for-length trajectories. The authors suggest that long-term follow-up is needed to determine if the decreased height trajectories of MA exposed children continues into later adulthood.

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