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

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.

Disclosure The speaker has no conflicts of interest.

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

Methamphetamine

FETAL EFFECTS

Fetal Development Embryonic Period

Fetal Development Fetal Period

Brain development

Brain development

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

US Dept HHS, Office Surgeon General, 2016

US Dept HHS, Office Surgeon General, 2016

US Dept HHS, Office Surgeon General, 2016

US Dept HHS, Office Surgeon General, 2016

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

Roos et al., 2014

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

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

NEONATAL EFFECTS

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

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

Badiani et al., 2011

Badiani et al., 2011

Badiani et al., 2011

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

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

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

LONGER-TERM EFFECTS

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

IDEAL Study Smith et al., 2015

NZ IDEAL Study Smith et al., 2015

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

Adjusted height trajectories Zabaneh et al., 2012

Roos et al., 2014

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

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

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

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

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

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

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

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

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

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

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

Neurobehavior Exposed (N=31) Unexposed (N=35) P-value Age (yr) 8.1 8.4 NS 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

CONFOUNDING

Confounding CAUSE EFFECT

Confounding ? CAUSE EFFECT CONFOUNDER

MOM BABY

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

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

Physical growth Abar et al., 2014

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

SUMMARY/CONCLUSIONS

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

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

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

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