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Identifying Risk of Severe Neonatal Abstinence Syndrome Among - - PowerPoint PPT Presentation

Sep 25, 2022 444 likes •633 views

Identifying Risk of Severe Neonatal Abstinence Syndrome Among Poly-Substance Exposed Infants Lauren Sanlorenzo MD Perinatal-Neonatal Fellow, Division of Neonatology Monroe Carrell Jr. Childrens Hospital at Vanderbilt Disclosures No

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Identifying Risk of Severe Neonatal Abstinence Syndrome Among Poly-Substance Exposed Infants

Lauren Sanlorenzo MD Perinatal-Neonatal Fellow, Division of Neonatology Monroe Carrell Jr. Children’s Hospital at Vanderbilt

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Disclosures

  • No disclosures to report
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Neonatal Abstinence Syndrome

  • Postnatal opioid withdrawal syndrome
  • Characterized by hyperactivity of central and

autonomic nervous system and gastrointestinal tract

  • Emerging public health crisis across the USA

McQueen et al. NEJM. 2016 Patrick et al. J Perinatol. 2015

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Neonatal Abstinence Syndrome- 2

  • Variable disease severity among opioid

exposed infants

  • Poly-substance use is common among opioid

using pregnant women

  • Benzodiazepine co-exposure may influence

NAS severity

Fitzsimons et al. J Sub Abuse Tx 2007 Dryden et al. BJOG 2009 Cleary et al Addiction 2012

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Hypothesis

  • The prevalence of antenatal benzodiazepine

exposure is higher among infants with pharmacologically treated NAS compared to infants with non-pharmacologically treated NAS.

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Methods

  • Study Design: nested case-control study
  • Population: woman and infants enrolled in

TennCare, Tennessee’s Medicaid program, in 2009-2011

  • Data Source: prescription and hospital claims

linked to vital statistics, hospital records, and toxicology tests

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Primary Study Base

  • Inclusion Criteria:

– Mother was 15-44 years old at the time of delivery – Mother enrolled in TennCare at least 30 days before delivery – Infant enrolled in TennCare within 30 days of delivery – Infants born between January 1, 2009 and December 31, 2011

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Methods

112,847 maternal-infant dyads ICD-9-CM 779.5 1,086 maternal-infant dyads validated standardized adjudication process

CASES: n=598 Pharmacologically treated NAS, LOS >5 days CONTROLS: n=224 Non-pharmacologically treated NAS

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Exposure Definition

  • Benzodiazepine exposure during pregnancy:

– Self-report of benzodiazepine use during pregnancy – Positive maternal urine toxicology test at time of delivery – Positive infant toxicology test at time of delivery (Urine, Meconium, Umbilical Cord, Blood)

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Maternal Characteristics

Maternal Characteristics Non- pharmacologically treated NAS (CONTROLS) n=224 Pharmacologically treated NAS (CASES) n=598 Age, yrs (mean) 25.5 26.2 Education, yrs (mean) 12 12 Race n (%) n (%) Black 4 (1.8) 15 (2.5) White 219 (98) 597 (97) Depression or Anxiety 120 (20) 41 (18) Hepatitis C Infection* 19 (8) 84 (14) * p-value <0.05

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Infant Characteristics

Infant Characteristics Non- pharmacologically treated NAS n (%) Pharmacologically treated NAS n (%)

Preterm (<37weeks) 41 (18) 92 (15) Low Birth Weight (<2500g) 50 (22) 131 (21) Female 110 (49) 247 (45) Respiratory Complications* 44 (19) 165 (27)

* p-value <0.05

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Cohort Exposed to Multiple Opioid Preparations

2% 37% 20% 40% 6% 48% 20% 35%

No Identified Opioid Exposure Short Acting Opioid Exposure Long Acting/MT Opioid Exposure Short Acting and Long Acting/MT Exposure Cases Controls

MT- Maintenance Opioid Therapy

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Poly-substance Exposed Infants

Exposure Non- pharmacologically treated NAS n (%) Pharmacologically Treated NAS n(%) p- value Tobacco 176 (78) 471 (82) 0.25 Marijuana 68 (30) 155 (25) 0.20 Cocaine 19 (8) 66 (11) 0.28 Methamphetamine 5 (2) 20 (3) 0.41 Phencyclidine 2 (0.9) 9 (1.3) 0.60 Benzodiazepines 69 (30) 245 (40) 0.01 SSRIs 33 (14) 102 (17) 0.42

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Benzodiazepine Exposure Increases Odds of Severe NAS

Exposure aOR 95% CI Female 0.86 0.62-1.18 Low Birth Weight (<2500g) 1.08 0.70-1.66 Preterm (<37wks) .71 0.44-1.13 Short Acting Opioid 1.67 1.12-2.47 Long Acting/Maintenance Opioid 2.07 1.46-2.93 Tobacco 1.18 0.79-1.75 SSRI 1.16 0.75-1.81 Benzodiazepine 1.50 1.08-2.13 THC 0.79 0.55-1.13 Cocaine 1.33 0.76-2.32 Gabapentin 1.67 0.46-6.0 Maternal Hepatitis C 1.54 0.90-2.65

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Conclusions

  • Benzodiazepine exposure is common in a

population based cohort of infants with NAS

  • Overall, after accounting for multiple

exposures, benzodiazepine exposure is independently associated with NAS severity

  • Population based methods overcame many of

the limitations of prior work, demonstrating this relationship in univariate and multivariate analysis

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Limitations

  • Data set restricted to one state, limiting

generalizability

  • Benzodiazepine prescription claims limited

during the study period; non-differential exposure misclassification

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Implications

  • Providers caring for opioid-dependent

pregnant women should be aware of adverse neonatal effects of antenatal benzodiazepine exposure

  • Tools used to predict NAS severity should

account for benzodiazepine exposure

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Thank you

Mentorship Team

  • Mentor

– Stephen W. Patrick MD MPH MS

  • Research Team

– William O. Cooper MD MPH – Faouzi Maalouf MD – Judith Dudley – Shannon Stratton

  • Funding:
  • NICHD T32HD060554

(Cooper)

  • NIDA K23DA038720

(Patrick)

  • John and Leslie Hooper

Neonatal-Perinatal Endowment Fund