Two Children with Developmental Delay and Behavioral Problems

Pediatric Pathways

Two Children with Developmental Delay and Behavioral Problems

After reading this article and answering the review questions the reader will be able to:

  1. Identify the most common preventable cause of intellectual and behavioral disabilities in children
  2. Describe the range of potential effects of prenatal alcohol exposure which constitute the fetal alcohol spectrum disorders (FASD)
  3. Answer: “How much alcohol is safe to drink during pregnancy?”
  4. Access and navigate the American Academy of Pediatrics FASD Toolkit

Case 1

Myra and Jon are parents of a 4-year-old boy they adopted two years ago from a Russian orphanage. They were told he was small at birth but have no other information about his biological family, the pregnancy, or his birth. Myra describes the orphanage as “one of the good ones,” with nutritious food, one-on-one attention, and a play room providing developmentally appropriate toys and opportunities for children to interact.

At the time of his adoption, they were aware of delays in his growth and development but were assured that these were common among children in the orphanage and were hopeful he would thrive under their care. His weight gain has improved, but he remains below the 10th percentile for height and is not catching up developmentally. Now enrolled in a 4K/early childhood program, he seems withdrawn and gets agitated when interacting with other children. His teachers report that he seems “lost” during class activities.

A developmental assessment confirms delays in several domains. In clinic, you note mildly unusual facial characteristics including small eyes, a smooth philtrum, and a thin upper lip. Chromosomal microarray analysis is ordered and results are normal.

Case 2

Elana is a 12-year-old girl who is struggling in school; she has special education support for math and an aid for several other classes, but seems to be at the limit of what she is able to do. She often loses concepts she had previously grasped and has to work very hard to relearn them. This is frustrating for her and she acts out in disruptive ways at school and at home. She is socially isolated, with just one or two “friends” who know she is gullible and often get her in trouble.

Her parents have long histories of heavy alcohol abuse, but her mother entered a treatment program when Elana was born and is celebrating her sobriety. Even before the pregnancy she had been aware that the most important time to avoid drinking was during the first trimester. Knowing this, she stopped drinking altogether as soon as she knew she was pregnant and didn’t start again until 14 weeks, then limiting herself to only two drinks per day.

Elana was appropriately grown at birth and had no congenital anomalies. She has grown normally throughout childhood. In clinic, you note that her facial features are completely normal.

Fetal Alcohol Syndrome

Alcohol is the most prevalent of all teratogens, and is among the most potent. The effects of prenatal exposure typically have greater long-term impact on the lives of affected individuals than those of exposures to methamphetamine, cocaine or heroin. The most recognizable manifestation is fetal alcohol syndrome (FAS), the most common preventable cause of intellectual disability. FAS is defined by diagnostic criteria set forth by the National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect (FAE) in 2004:

  1. Growth impairment: length/height or weight below the 10th percentile
  2. Characteristic facial features: short palpebral fissures, smooth philtrum, and thin upper lip
  3. Central nervous system anomalies: microcephaly, structural brain anomalies, or functional deficits

Note that a history of prenatal alcohol exposure is not listed here. This was excluded to acknowledge the difficulties frequently encountered when attempting to obtain accurate and complete information about alcohol use by the mother.

Even without information about his prenatal alcohol exposure, the child described in the first case, satisfies these criteria, and the diagnosis of FAS is appropriate. Moreover, international adoption specialists familiar with Russian and Ukrainian orphanages consistently report that prenatal alcohol exposure is nearly universal among children in those institutions. Microarray analysis is reasonable given his delays and dysmorphism, but is not necessary when the diagnosis of FAS is clear.

Other Disorders – The Range of Effects of Prenatal Alcohol Exposure

Effects on brain development can be severe in the absence of growth impairment or characteristic facial features. These effects are often not evident on imaging and, yet, can result in substantial intellectual disabilities, other learning disabilities, and challenging patterns of behavior. Congenital anomalies such as heart defects, cleft palate, and vertebral abnormalities are also more common. The spectrum of effects of prenatal alcohol exposure encompasses growth, physical, developmental, and behavioral abnormalities, which are typically present throughout the life of the individual; only in a minority of instances do these satisfy the criteria for the diagnosis of FAS. Other diagnoses under the FAS umbrella include partial FAS, alcohol-related birth defects (ARBD) and alcohol-related neurodevelopmental disorder (ARND). Diagnostic criteria for these disorders were reviewed and amended by Hoyme et al; importantly, the diagnoses of ARBD and ARND require a confirmed history of alcohol exposure before birth.

As with most teratogens, dosage and timing are important determinants of the consequences of prenatal alcohol exposure. However, this is only true in a very general sense; there are loose correlations between the pattern and amount of maternal alcohol consumption and the likelihood and severity of effects, but no risk-free level of consumption has been identified.

In regard to timing, Elana’s mother, in the second case, is correct only in that exposures during the first trimester are most likely to affect structural development of many organs and tissues. Unfortunately the brain remains vulnerable to the effects of alcohol throughout the entire period of gestation, since active development of the cerebral architecture (neurogenesis, neuronal migration, synapse formation, myelination, etc.) continues through all three trimesters and into postnatal life.

Elana’s diagnosis is ARND, based on her learning and behavioral problems, and her mother’s self-reported history of drinking before the pregnancy was recognized and again from 14 weeks onward. Neuropsychological assessment can be extremely informative in characterizing the deficits in individuals with ARND, and for the development of effective interventions. As the importance of nutritional, genetic, epigenetic, and psychosocial factors in determining the effects of prenatal alcohol exposure is revealed, the multifactorial nature of this group of disorders is becoming clear.

It is still nevertheless true that, at least for the time being, the one factor which is both essential and can be prevented is the alcohol exposure itself. Wisconsin has the highest rates in the U.S. of binge drinking (23%) and overall alcohol consumption (68%) among women between the ages of 18 and 44 according to the State Department of Health Services.3 Alcohol consumption is an established risk factor for unintended pregnancies, and continued consumption results in alcohol exposure during critical periods of embryonic and fetal development.

Prevention takes substantial effort but is essential to reducing the impact of prenatal alcohol exposure, and the core message still holds true; there is no amount of alcohol that is known to be safe, no safe time during pregnancy to drink, and no safe type of alcohol to consume during pregnancy. But prevention alone is not sufficient.

CDC estimates of the incidence of FAS range from 0.2-1.5/1000 live births, while the incidence of the full range of FASD is estimated to be 9-10/1000 live births. In Wisconsin, this equates to dozens of children born each year with FAS, and hundreds of children in need of related medical care as well as developmental, educational and behavioral health services.

Interventions are now available that are based on an abundance of research on the neurobiology of FASD, and the body of evidence for their effectiveness is growing. There are however substantial barriers to diagnosis, which has led national agencies, including the CDC in partnership with the American Academy of Pediatrics (AAP), to make new efforts to raise FASD awareness and provide education and resources to providers in order to facilitate diagnosis and referral of children suspected of having these disorders.

One outcome of this joint effort has been the creation of an FASD Toolkit, available on the AAP website at www.aap.org/fasd. Under the “Identification, Diagnosis and Referral” heading is an algorithm which is a ready-reference and reminder of the things to consider in the assessment of children and adults who may have been affected by prenatal exposure to alcohol. With this tool and other education and awareness efforts, a wider array of providers who care for children will hopefully become comfortable with the assessment, and FASD diagnoses will become more widely available to children in Wisconsin and throughout the country.

What about the issue of low levels of exposure? Are we going too far by recommending complete abstinence?

From a purely biochemical and teratologic standpoint, there should be “threshold” levels below which alcohol consumption poses little or no risk to the developing embryo and fetus. Threshold levels have been established for many other teratogens. To take this to the extreme, it is improbable from a physiologic standpoint that a minute sip of wine at any point in the pregnancy poses a significant risk. However, there are three persisting problems.

First, as is repeated extensively throughout the FASD literature, no threshold level has been identified for prenatal alcohol exposure in humans. Second, based on the emerging multifactorial model of FASD, one would predict that, if there are thresholds, they differ between individual mothers and even between individual pregnancies, and we are far from being able to synthesize all of the factors involved to identify a risk-free level of consumption for any individual pregnancy. Third, this is not a simple biochemical or teratologic problem. Particularly for people who have difficulty controlling their use of alcohol, any advice from a health care provider that legitimizes a small amount of alcohol intake carries the risk of opening the door to heavier use than the provider intended.

All of this means that we as providers are not able to assure patients that any specific amount of alcohol use is safe during their pregnancy. Papers published in the last two years from the UK and Denmark,4,5 as well as articles in the popular press6 have led some to challenge the advice to abstain completely from alcohol use during pregnancy. The CDC, AAP, ACOG and others have responded to this information in the context of risk.

Acknowledging what is still unknown about the contribution of nutritional, genetic, epigenetic and other environmental factors that each play a role in the etiology of FASD, it is not possible to predict with any certainty the effect of a given exposure to a specific embryo or fetus. On the other hand, what is known is that the effects can be devastating and lifelong for the affected individual, and life-changing for the parents. The added prevention message is, “Why take the risk?” All of the professional groups mentioned above continue to recommend abstinence from alcohol use during pregnancy.

What about ARND? How do we know the neurobehavioral effects are due to the alcohol exposure?

This continues to be an important and difficult area of ongoing study. First, it is well established based on an abundance of data from controlled animal studies and clinical research that prenatal alcohol exposure can cause CNS deficits in the absence of growth and morphologic effects; it is clear that ARND exists. The question is how to identify it in an individual. Second, as neurobiological studies of FASD and neuropsychological assessments in children become more sophisticated, a pattern of deficits that is relatively specific to the effects of prenatal alcohol exposure is emerging.7

An ARND task force, modeled on the National task force on FAS/FAE*1 has been established, and there is a proposal in the DSM V to create a category of behavioral disorders related to prenatal alcohol exposure. If adopted, this will change the emphasis of the clinical categorization of the FASD from the physical effects to the developmental and behavioral effects. In the meantime, clinical judgment continues to be an important part of the assessment.

* FAE and “fetal alcohol effects” are terms that are no longer in use

Online Resources

Local resources based at the UW SMPH Department of Family Medicine and Community Health:

AAP: www.aap.org/fasd (navigate via the menu on the left)

CDC: http://www.cdc.gov/ncbddd/fasd/index.html

To schedule an appointment in the Medical Genetics or Biochemical Genetics Clinic, please call (608) 263-3301 or visit our website.

Go to CME questions

Back to top 

References

  1. Bertrand J, Floyd RL, Weber MK, O’Connor M, Riley EP, Johnson KA, Cohen DE, National task force on FAS/FAE. Fetal Alcohol syndrome: Guidelines for Referral and Diagnosis. Atlanta, GA: Centers for Disease Control and Prevention; 2004
  2. Hoyme HE, May PA, Kalberg WO, Kodituwakku P, Gossage P, Trujillo PM, Buckley DG, Miller JH, Aragon AS, Khaole N, Viljoen DL, Jones KL, Robinson L. A Practical Guide to Diagnosis of Fetal Alcohol Spectrum Disorders: Clarification of the 1996 Institute of Medicine Criteria. Pediatrics 2005; 115(1):39-47
  3. Wisconsin Department of Health Services, Division of Public Health and Division of Mental Health and Substance Abuse Services (2012). Wisconsin Epidemiological Profile on Alcohol and Other Drug Use. P-45718-12. Prepared by the Office of Health Informatics, Division of Public Health, in consultation with the Division of Mental Health and Substance Abuse Services and the University of Wisconsin Population Health Institute.
  4. Kelly YJ, Sacker A, Gray R, Kelly J, Wolke D, Head J, Quigley MA. Light drinking during pregnancy: still no increased risk for socioemotional difficulties or cognitive deficits at 5 years of age?
  5. Falgreen Eriksen H-L, Mortensen EL, Kilburn T, Underbjerg M, Bertrand J, Støvring H, Wimberley T, Grove J, Kesmodel US. The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5- year-old children. BJOG 2012; 119(10);1191 - 1200 DOI: 10.1111/j.1471-0528.2012.03394.x
  6. Oster E. Take Back Your Pregnancy. The Saturday Essay. Wall Street Journal, August 9, 2013: http://online.wsj.com/article/SB10001424127887323514404578652091268307904.html
  7. Mattson SN, Roesch SC, Glass L, Deweese BN, Coles CD, Kable JA, May PA, Kalberg WO, Sowell ER, Adnams CM, Jones KL, Riley EP, and the CIFASD. Further Development of a Neurobehavioral Profile of Fetal Alcohol Spectrum Disorders. Alcohol Clin Exp Res, 37(3), 2013: 517–528