1. Wisconsin Association for Perinatal Care
The Impact of Methamphetamine on Fetal Development and Newborn Behavior
Kyle Mounts, MPH
Program Director
Wisconsin Association for Perinatal Care
Madison, WI

2. Objectives
Describe the effects of methamphetamine on the developing fetus.
Describe the effects of methamphetamine on newborn behavior.
Describe other factors that can affect fetal and newborn outcomes.

3. Disclosure
The speaker has no conflicts of interest.

4. Overview Introduction Effects of methamphetamine on the fetus
Effects of methamphetamine on the newborn
Longer-term effects of methamphetamine
Confounding
Summary

5. Methamphetamine

6. FETAL EFFECTS

7. Fetal Development
Embryonic
Period

8. Fetal Development
Fetal
Period

9. Brain development

10. Brain development

11. Stimulants Increase dopamine in reward circuit
Increase dopamine in regions responsible for attention and focus on tasks
Cause release of norepinephrine, causing a user to feel energized
US Dept HHS, Office Surgeon General, 2016

12. US Dept HHS, Office Surgeon General, 2016

13. US Dept HHS, Office Surgeon General, 2016

14. US Dept HHS, Office Surgeon General, 2016

15. US Dept HHS, Office Surgeon General, 2016

16. Teratogenicity
Some reports suggest higher prevalence of congenital malformations, such as cleft palate and limb defects.
Case-control and prospective studies have not confirmed the findings.
Risk of teratogenicity: low
Dinger et al., 2017

17. Roos et al., 2014

18. Fetal growth Exposed ((N=204) Unexposed (N=3501) P-value
Gestational age (wk)
38.6
39.1
<0.001
Male
110 (53.9%)
1791 (51.2%)
0.452
Birth weight (g)
3180
3369
0.154
Small for gestational age (%)
35 (17.3%)
310 (8.9%)
0.005
Nguyen et al., 2010

19. Neonatal outcomes Methamphetamine Exposed Control P-value
Gestational age (wk)
37.5
39.7
<0.001
Birth weight (g)
3427
3527 NS
Birth length (cm)
50.2
50.5
Head circumference (cm)
34.4
34.7
Tobacco/Meth-exposed
Birth weight
3336
3573
0.01
Birth length
49.8
50.7
34.1
34.9
Smith et al., 2003

20. NEONATAL EFFECTS

21. Withdrawal Lethargy Abnormal sleep patterns Poor movement quality
Poor sucking/excessive sucking
Jitteriness
Polysubstance use may be associated with other symptoms
Dinger et al., 2017

22. Withdrawal (Pt II)
Why is withdrawal from methamphetamine different from withdrawal from opioids?
Badiani et al., 2011

23. Badiani et al., 2011

24. Badiani et al., 2011

25. Badiani et al., 2011

26. Neurobehavior 380 infants (PME 185)
NICU Network Neurobehavioral Scale (NNNS)
Within first 5 days
At one month age
Kiblawi et al., 2014

27. NICU Network Neurobehavioral Scale (NNNS)
Habituation
Attention
Arousal
Regulation
Handling
Quality of movement
Excitability
Lethargy
Nonoptimal reflexes
Asymmetric reflexes
Hypertonicity
Hypotonicity
Stress/Abstinence
Kiblawi et al., 2014

28. Neurobehavior Time (birth to one-month) Exposure Time/exposure
Higher arousal
Quality of movement
Reduced lethargy
Exposure
No significant effects
Time/exposure
Arousal
Total stress
Kiblawi et al., 2014

29. LONGER-TERM EFFECTS

30. IDEAL Study Infant Development, Environment, and Lifestyle
Recruitment from 4 sites over 2-year period
Screened: 34,833
Eligible: 17,961
Consented: 3705
Longitudinal follow-up: 412
Exposed: 204
Matched comparisons: 208
Smith et al., 2015

31. IDEAL Study
Smith et al., 2015

32. NZ IDEAL Study
Smith et al., 2015

33. Child Development Physical Motor Cognitive/intellectual
Social-emotional
Behavioral
Language and communication

34. Adjusted height trajectories
Zabaneh et al., 2012

35. Roos et al., 2014

36. PDMS-2 by Methamphetamine Exposure
Exposed
Control
P-value
1 year
Gross motor
103.8
103.6
0.630
Fine motor
104.9
106.2
0.240
Grasping
10.2
10.6
0.027
3 years
95.3
94.8
0.492
98.8
0.697
Smith et al., 2011

37. Neurodevelopment Exposed Control P-value Length (cm) 3 years 95.3 96.8
0.009
Weight (cm)
2 years
12859
13366
0.035
Head circumference (cm)
1 year
46.7
47.2
0.036
PDI
87.1
94.3
0.015
Wouldes et al., 2014

38. Cognitive, language, behavioral outcomes
Relationship between infant temperament, environmental risk, and cognitive, language, and behavioral outcomes
12 mos: Infant Behavioral Questionnaire
“Easy” and “difficult” temperament profiles
36 mos: Child Behavior Checklist, Bayley Scales of Infant Development, Preschool Language Scale-4
Derauf et al., 2011

39. Cognitive, language, behavioral outcomes
Internalizing and externalizing behaviors were:
Lower with easy temperament
Higher with increased environmental risk
High-risk environment/temperament factors not related to cognitive/motor outcomes
PME not associated with 3-yr outcomes; did not alter protective effects of easy temperament
Derauf et al., 2011

40. Behavioral/cognitive outcomes
298 mother-infant pairs (151 PME)
Follow-up at 7.5 years
Connors Parent Rating Scale-Revised
Diaz et al., 2014

41. Behavioral/cognitive outcomes
Exposed
(N=151)
Comparison
(N=147)
P-value
Oppositional
54.6
52.4
0.355
Cognitive problems
54.8
51.6
0.048
Hyperactivity
57.2
54.3
0.129
ADHD index
55.2
52.9
0.226
Diaz et al., 2014

42. Behavioral/cognitive outcomes
PME was associated with increased cognitive problems, which may affect academic achievement and lead to increased negative behavioral outcomes
Additional studies on how prenatal methamphetamine exposure impacts behavioral and cognitive outcomes during childhood are still necessary.
Diaz et al., 2014

43. Neurobehavioral disinhibition (ND)
Deficits
Behavioral and emotional control
Executive function
To what extent does methamphetamine exposure predict ND?
To what extent does early adversity mediate the relationship?
Abar et al., 2013

44. Neurobehavioral disinhibition (ND)
320 mother-infant dyads (162 PME)
Followed from birth to 6.5 years age
Results
PME associated with behavioral and emotional control at 5 years, which was associated with executive function deficits at 6.5 years
Early adversity (birth-year 3) significantly mediated the relationship between PME and ND
Implications: Prevention and support
Abar et al., 2013

45. Behavior 330 children (PME 166) Child Behavior Checklist Results:
At 3-years age and 5-years age
Results:
Increased emotional reactivity and anxious/depressed problems at both ages
Externalizing and attention-deficit/hyperactivity disorder problems and withdrawn behavior at age 5
LaGasse et al., 2012

46. ADHD 301 mother-infant pairs (PME 153)
Conners’ Kiddie Continuous Performance Test (K-CPT) at 5.5 years
Results: Subtle differences in some aspects of testing
Conclusion: Infants with PME exhibit indicators of risk for ADHD and warrant monitoring
Kiblawi et al., 2013

47. Neurobehavior Exposed (N=31) Unexposed (N=35) P-value Age (yr) 8.1 8.4NS
Male (%)
46.7
57.1
Ethnicity (% non-Caucasian)
20.0
25.7
Below grade level (%)
25.9
3.0
<0.05
Below reading level (%)
38.5
20.6
ADHD (%)
11.8
<0.005
Piper et al., 2011

48. CONFOUNDING

49. Confounding
CAUSE
EFFECT

50. Confounding ?
CAUSE
EFFECT
CONFOUNDER

51. MOM
BABY

52. GENETICS INCARCERATION ENVIRONMENT STRESS DRUGS SUPPORT MENTAL ILLNESS
MOM
STRESS
DRUGS
BABY
SUPPORT
MENTAL ILLNESS

53. Physical growth
Compare effects of PME on infant/child growth between US and New Zealand
Sample
US: 204 children with PME; 212 controls
NZ: 108 children with PME; 115 controls
Abar et al., 2014

54. Physical growth
Abar et al., 2014

55. Adversity and behavior
Assess relationship between PME, behavior problems, and early adversity
412 mother-infant pairs (PME 204)
PME associated with increased early adversity score and with increased externalizing, rule-breaking behavior, and aggressive behavior
Early adversity significantly mediated relationship between PME and behavior
Eze et al., 2016

56. SUMMARY/CONCLUSIONS

57. Summary Effects of methamphetamine on the developing fetus
Effects of methamphetamine on newborn behavior
Other factors that can affect fetal and newborn outcomes

58. Surgeon General’s report
Enhanced public education
Widespread implementation of evidence-based prevention policies and programs
Improved access to evidence-based treatment services, integrated with mainstream health care
Recovery support services
Research-informed public policies and financing strategies
US Dept HHS, Office Surgeon General, 2016

59. Public health systems approach
Define the problem through systematic data collection
Identify risk and protective factors
Public/private sector collaboration
Broad implementation of effective interventions and recovery support
Monitor impact of interventions
US Dept HHS, Office Surgeon General, 2016

60. If questions, please feel free to contact: mounts@perinatalweb.org