Association between Neonatal Abstinence Syndrome and Congenital Anomalies in the United States

 

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Abstract

Objective Studies exploring the relationship between neonatal abstinence syndrome (NAS) and congenital anomalies (CA) in the United States are limited given the small sample size or data prior to the opioid epidemic. We aimed to determine if there is an association between NAS and CA in a nationally representative cohort of newborn hospitalization in the United States.

Study Design This was a cross-sectional analysis of NAS-related hospitalizations within the 2016 Kids Inpatient Database. International Classification of Diseases (ICD-10-CM) diagnostic codes were used to identify NAS hospitalizations and those with and without CA. The primary outcome was the odds of CAs in NAS hospitalizations. Multivariate survey logistic regression was used to analyze the relationship between NAS and CA.

Results Among 3.7 million newborn hospitalizations, 25,394 had NAS (6.7 per 1,000). The prevalence of any CA was higher in those with NAS when compared with non-NAS hospitalizations (10.3 vs. 4.9%; odds ratio = 2.27; 95% confidence interval [CI]: 2.13–2.43). Adjusted analysis showed similar results (adjusted odds ratio: = 1.83, CI: 1.71–1.95). NAS hospitalizations with CA had a higher mortality rate (0.6 vs 0.04%, p < 0.0001) and higher resource use.

Conclusion This nationwide study shows that NAS may be associated with increased odds of CAs, suggesting that NAS may be a risk factor for increased morbidity in the newborn period.

Key points

• 1 in 10 newborns with NAS had at least one congenital anomaly.

• NAS hospitalization with congenital anomalies had higher resource use and mortality.

• Pediatricians caring for newborns with NAS should have a high index of suspicion for birth defects.

Note

Prior presentation of abstract or Poster: An abstract of this study was accepted for poster presentation at the 2022. The Eastern Society for Pediatric Research (ESPR) Meeting and Oral presentation at the 2021 Pediatric Academic Societies (PAS) meeting.

Data Sharing Statement: Deidentified individual participant data will not be made available. The raw data were obtained from the Agency for Healthcare Research and Quality ( https://www.hcupus.ahrq.gov )

Authors' Contributions

V.G.L., N.P., J.P., S.P. conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. C.A.-D., H.D., G.A.C., I.O., and A.O.A conceptualized and designed the study, designed the data collection instruments, collected data, performed the initial analyses, and reviewed and revised the manuscript. P.B., K.D., and F. D.-S. conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Publication History

Received: 15 June 2022

Accepted: 08 November 2022

Article published online:
26 December 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

• References

• 1 Kocherlakota P. Neonatal abstinence syndrome. Pediatrics 2014; 134 (02) e547-e561
  CrossrefPubMedGoogle Scholar
• 2 National Institute on Drug Abuse; National Institutes of Health. U.S. Department of Health and Human Services. Dramatic Increases in Maternal Opioid Use and Neonatal Abstinence Syndrome | NIDA Archives. . Accessed May 16, 2022 at: https://archives.drugabuse.gov/trends-statistics/dramatic-increases-in-maternal-opioid-use-neonatal-abstinence-syndrome
  PubMedGoogle Scholar
• 3 Broussard CS, Rasmussen SA, Reefhuis J. et al; National Birth Defects Prevention Study. Maternal treatment with opioid analgesics and risk for birth defects. Am J Obstet Gynecol 2011; 204 (04) 314.e1-314.e11
  CrossrefPubMedGoogle Scholar
• 4 Auger N, Luu TM, Healy-Profitós J, Gauthier A, Lo E, Fraser WD. Correlation of neonatal abstinence syndrome with risk of birth defects and infant morbidity. J Stud Alcohol Drugs 2018; 79 (04) 553-560
  CrossrefPubMedGoogle Scholar
• 5 Fornoff J, Sandidge T. Prevalence of birth defects among infants with neonatal abstinence syndrome in Illinois, 2015-2016. Birth Defects Res 2021; 113 (02) 134-143
  CrossrefPubMedGoogle Scholar
• 6 Brogly SB, Turner S, Lajkosz K. et al. Infants born to opioid-dependent women in Ontario, 2002-2014. J Obstet Gynaecol Can 2017; 39 (03) 157-165
  CrossrefPubMedGoogle Scholar
• 7 Danis III DO, Bachrach K, Piraquive J, Marston AP, Levi JR. Cleft lip and palate in newborns diagnosed with neonatal abstinence syndrome. Otolaryngol Head Neck Surg 2021; 164 (01) 199-205
  CrossrefPubMedGoogle Scholar
• 8 Mullens CL, McCulloch IL, Hardy KM, Mathews RE, Mason AC. Associations between orofacial clefting and neonatal abstinence syndrome. Plast Reconstr Surg Glob Open 2019; 7 (01) e2095
  CrossrefPubMedGoogle Scholar
• 9 Lind JN, Interrante JD, Ailes EC. et al. Maternal use of opioids during pregnancy and congenital malformations: a systematic review. Pediatrics 2017; 139 (06) 20164131
  CrossrefPubMedGoogle Scholar
• 10 Hussaini KS, Drummond D, Bartoshesky LE. et al. Assessing the relationship between neonatal abstinence syndrome and birth defects in Delaware. Birth Defects Res 2021; 113 (02) 144-151
  CrossrefPubMedGoogle Scholar
• 11 Hospitalizations for Neonatal Abstinence Syndrome in Mississippi. Accessed February 27, 2021 at: https://msdh.ms.gov/msdhsite/_static/resources/7001.pdf
  PubMed
• 12 Bunn TL, Ouyang BJ, Slavova S. Newborn congenital malformations associated with prenatal exposure to drugs in Kentucky, 2009-2013. South Med J 2016; 109 (02) 124-129
  CrossrefPubMedGoogle Scholar
• 13 Agency for Healthcare Research and Quality. Introduction to the HCUP Kids' Inpatient Database (KID) 2016. Accessed May 16, 2022 at: www.hcup-us.ahrq.gov/db/nation/kid/KID_2016_Introduction.pdf
  PubMedGoogle Scholar
• 14 Healthcare Cost and Utilization Project (HCUP) KID Notes. Accessed May 16, 2022 at: https://www.hcup-us.ahrq.gov/db/vars/i10_hospbrth/kidnote.jsp
  PubMed
• 15 Hirai AH, Ko JY, Owens PL, Stocks C, Patrick SW. Neonatal abstinence syndrome and maternal opioid-related diagnoses in the US, 2010-2017. JAMA 2021; 325 (02) 146-155
  CrossrefPubMedGoogle Scholar
• 16 Strahan AE, Guy Jr. GP, Bohm M, Frey M, Ko JY. Neonatal abstinence syndrome incidence and health care costs in the United States, 2016. JAMA Pediatr 2020; 174 (02) 200-202
  CrossrefPubMedGoogle Scholar
• 17 Healthcare Cost and Utilization Project (HCUP) KID Notes. Accessed October 10, 2022 at: https://www.hcup-us.ahrq.gov/db/vars/hosp_location/kidnote.jsp
  PubMed
• 18 Healthcare Cost and Utilization Project (HCUP) KID Notes. Accessed October 10, 2022 at: https://www.hcup-us.ahrq.gov/db/vars/hosp_locteach/kidnote.jsp
  PubMed
• 19 Introduction to the HCUP KIDS' Inpatient Database (KID). 2019. Accessed October 10, 2022 at: https://www.hcup-us.ahrq.gov/db/nation/kid/kid_2019_introduction.jsp#table4
  PubMed
• 20 HCUP-US Cost-to-Charge Ratio for Inpatient Files. Accessed February 2, 2021 at: https://www.hcup-us.ahrq.gov/db/nation/nis/NISIntroduction2017.pdf
  PubMed
• 21 U.S. Bureau of Labor Statistics. CPI Inflation Calculator. Accessed April 22, 2020 at: https://www.bls.gov/data/inflation_calculator.htm
  PubMedGoogle Scholar
• 22 Asdjodi S, Rubarth RB, Hardy J, Lee H. The effects of opioids during pregnancy: a literature review. Georg Med Rev 2020; 4 (01) 16759
  PubMedGoogle Scholar
• 23 Wang G, Wang H, Yang Y, Wong TM. κ-opioid receptor stimulation inhibits growth of neonatal rat ventricular myocytes. Eur J Pharmacol 2004; 498 (1-3): 53-58
  CrossrefPubMedGoogle Scholar
• 24 Medication-Assisted Treatment (MAT) | SAMHSA. Accessed May 24, 2022 at: https://www.samhsa.gov/medication-assisted-treatment
  PubMedGoogle Scholar
• 25 Prevent Opioid Use Disorder. CDC's Response to the Opioid Overdose Epidemic. CDC. Accessed May 20, 2022 at: https://www.cdc.gov/opioids/overdoseprevention/opioid-use-disorder.html
  PubMedGoogle Scholar
• 26 Patrick SW, Schiff DM. Committee on substance use and prevention. A public health response to opioid use in pregnancy. Pediatrics 2017; 139 (03) e20164070
  CrossrefPubMedGoogle Scholar
• 27 Short TD, Stallings EB, Isenburg J. et al. Gastroschisis trends and ecologic link to opioid prescription rates—United States, 2006-2015. MMWR Morb Mortal Wkly Rep 2019; 68 (02) 31-36
  CrossrefPubMedGoogle Scholar
• 28 Goyal S, Saunders KC, Moore CS. et al. Identification of substance-exposed newborns and neonatal abstinence syndrome using ICD-10-CM - 15 Hospitals, Massachusetts, 2017. MMWR Morb Mortal Wkly Rep 2020; 69 (29) 951-955
  CrossrefPubMedGoogle Scholar
• 29 Coleman PK. Diagnosis of fetal anomaly and the increased maternal psychological toll associated with pregnancy termination. Issues Law Med 2015; 30 (01) 3-23
  PubMedGoogle Scholar

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