Assessment of the Standardized Surveillance Case Definition for Neonatal Abstinence Syndrome by the Council of State and Territorial Epidemiologists, 4 Jurisdictions, 2020-2021

Abstract

Objectives:

In 2019, the Council of State and Territorial Epidemiologists ratified a multitiered standardized surveillance case definition (SSCD) for neonatal abstinence syndrome (NAS) to minimize variability in definitions across states. This evaluation of the tier 1 NAS SSCD aimed to identify common challenges and opportunities for enhancement to support consistent implementation of the definition.

Methods:

This mixed-methods analysis consisted of 3 virtual focus groups in March 2021 with site principal investigators, medical record abstractors, and data analysts (1 focus group each) from 4 jurisdictions piloting the tier 1 NAS SSCD. We analyzed focus group transcripts to create a codebook. We collected written reports in February 2022 from the 4 jurisdictions, conducted thematic analysis of focus group transcripts and written reports to identify themes, and collected surveillance data on infants identified with NAS born from January 2020 through December 2021 from the pilot sites. We analyzed surveillance data to further inform identified themes. We examined agreement among tier 1 classifications assigned independently by each pilot site and the Centers for Disease Control and Prevention to cases of NAS.

Results:

Three major themes emerged in the data: challenges abstracting data on withdrawal signs from the medical record, difficulty determining the time frame of prenatal substance exposure, and challenges assigning case classifications. In a comparison of tier 1 classifications assigned by the Centers for Disease Control and Prevention and the sites, 82.1% of cases in the dataset were concordant.

Conclusions:

We identified several opportunities to modify the SSCD to promote consistency and ease implementation across jurisdictions. Promoting consistent implementation supports comparability of NAS incidence estimates across jurisdictions, evaluation of prevention efforts, and allocation of resources to support families.

Neonatal abstinence syndrome (NAS) is a constellation of symptoms that an infant can experience following birth after in utero exposure to some substances, particularly opioids. The national prevalence of NAS increased through 2017; recent national discharge data suggest, however, that in 2018 it began to decrease but remains high and varies considerably by state.^1-3 In 2020, the estimated national NAS rate was 6.3 per 1000 hospital births. ³ Neonatal opioid withdrawal syndrome is an emerging term for opioid-specific exposure, yet the term NAS remains dominant in the literature. Although NAS is most notably associated with opioids, benzodiazepines, and barbiturates (OBBs), limited evidence suggests that it can occur from other substances as well. ⁴

In spring 2019, the Council of State and Territorial Epidemiologists (CSTE) ⁵ conducted an environmental scan to understand how states define and operationalize NAS surveillance; results of this scan found that reporting and data requirements varied by jurisdiction. In response to the environmental scan, CSTE ratified a standardized surveillance case definition (SSCD) for NAS to minimize variability across states. ⁶ This definition includes 2 implementation tiers: tier 1 uses real-time case reporting to public health legal authorities and tier 2 is based on administrative data. The tier 1 CSTE NAS SSCD (hereinafter, the SSCD) identifies and classifies infants with NAS by diagnosis/chief concern (“chief complaint” in the SSCD), withdrawal signs, maternal history of substance or prescription medication (MSPM) use, and laboratory evidence of exposure.

The SSCD includes confirmed, probable, and suspect case classifications for public health surveillance purposes. ⁶ Probable and suspect classifications are further categorized into probable types 1 and 2 and suspect types 1-5 for a total of 8 classifications. Each classification criterion requires different combinations of evidence of exposure and evidence of withdrawal (Table 1). Evidence of exposure is defined as MSPM use or positive maternal or infant laboratory testing results for OBB or non-OBB substances. Evidence of withdrawal is defined as NAS diagnosis/chief concern or clinical signs of withdrawal. Confirmed and probable classifications focus on OBB exposures and require the presence of ≥3 of 17 SSCD withdrawal signs. Suspect classifications can include exposure to OBBs, non-OBBs, and unknown substance types; suspect types 1-3 require the presence of ≥3 of 17 SSCD withdrawal signs, and suspect types 4 and 5 require 1 or 2 signs. ⁶ For example, for a case to be confirmed, there must be confirmatory laboratory evidence of OBBs in the neonate and either ≥3 NAS withdrawal signs or mention of a diagnosis/chief concern of NAS.

Table 1.

CSTE’s standardized case definition of tier 1 NAS: classification types by required elements of surveillance criteria ^a

Evidence: criteria	Confirmed	Probable type		Suspect type
		1	2	1	2	3	4	5
Evidence of withdrawal
Diagnosis/chief concern OR ≥3 signs clinically compatible with NAS	R	R	R	R	R	R
1 or 2 signs clinically compatible with NAS							R	R
Evidence of exposure
OBB: infant positive toxicology	R
OBB: maternal history within 4 wk of delivery		R					R
OBB: maternal positive toxicology			R					R
Non-OBB: maternal history within 4 wk of delivery				R
Non-OBB: maternal positive toxicology						R
Unknown: maternal history within 4 wk					R
Additional criteria
And no or unknown laboratory results in the neonate		R	R	R	R	R	R	R
And no or unknown maternal laboratory results				R	R		R
Absence of another known cause/diagnosis	R	R	R	R	R	R	R	R

Abbreviations: CSTE, Council of State and Territorial Epidemiologists; NAS, neonatal abstinence syndrome; OBB, opioids, benzodiazepines, and/or barbiturates; R, required.

^aData source: Council of State and Territorial Epidemiologists. ⁶

This mixed-methods study evaluated implementation of the tier 1 component of the SSCD by pilot site health departments to understand sites’ perceived challenges with implementation of the SSCD and opportunities for enhancement.

Methods

This analysis consisted of 3 approaches: 2 approaches to assess data qualitatively and a third approach to examine data quantitatively. First, we held 3 structured focus groups virtually in March 2021 with site principal investigators, medical record abstractors, and data analysts (1 focus group each) to assess the challenges and opportunities of using the SSCD. Focus group sessions were led by an impartial facilitator (C.G.) and lasted approximately 60 minutes; they were audio recorded and transcribed. Eleven individuals participated from each of the 4 sites; 3 participated in >1 focus group because they held several project roles. We used deductive and inductive coding to create a codebook from the focus groups; 2 analysts (M.C., D.O.) from the Centers for Disease Control and Prevention (CDC) used established methods for coding. ⁷ Second, in February 2022, we collected written reports from all site principal investigators; we structured reports with 7 prompts so that we would obtain standardized results. The prompts included topics such as challenges with implementing the SSCD, data accessibility and usability, partnership development, general trends, and external challenges to data collection and project advancement. We then applied the codebook to the reports. We used thematic analysis to assess and organize coded segments from both qualitative sources into minor themes. Minor themes from the qualitative data collected in 2022 were similar to themes collected in 2021; therefore, we made no distinction in time between the data sources. The analysis was reviewed by CDC and was conducted consistent with applicable federal laws and CDC policies (45 CFR part 46; 21 CFR part 56; 42 USC §241d; 5 USC §552a; 44 USC §3501 et seq).

In addition to qualitative data, we collected quantitative data. Site principal investigators securely submitted surveillance data to CDC on infants identified with NAS born from January 2020 through December 2021. We calculated the frequency with which SSCD criteria were used to document evidence of withdrawal in the infant (NAS diagnosis/chief concern, clinical signs of withdrawal) or evidence of exposure during pregnancy (MSPM use, maternal or infant laboratory evidence). For each case of NAS, CDC analysts (M.C., J.S.) and sites independently assigned a classification (confirmed, probable type 1 or 2, or suspected types 1-5). Sites were responsible for providing a classification for their cases before submitting their data; CDC used all available data provided for a case to assign classifications. We calculated descriptive statistics and used cross-tabulation to compare classification assignments between sites and CDC. We conducted all analyses in R Studio version 4.1.0 (R Foundation for Statistical Computing) and SAS version 9.4 (SAS Institute Inc).

Two CDC analysts (M.C., D.O.) triangulated the data to identify major themes between quantitative and qualitative sources. We synthesized quantitative findings and qualitative minor themes into major themes that were consistent across all data sources; this process included identifying where challenges raised in the focus groups and progress reports were supported by the quantitative data. ⁸

Results

Three major themes emerged from analysis of the focus groups and written reports: challenges abstracting data on withdrawal signs from the medical record, difficulty determining the time frame of prenatal substance exposure, and challenges assigning case classifications (Table 2).

Table 2.

Concerns about CSTE’s standardized case definition of tier 1 NAS ^a : major themes and illustrative quotations from 4 pilot sites, ^b 2020-2021

Major theme	Illustrative quotations
Evidence of withdrawal—documenting withdrawal signs	• NAS symptoms don’t always correlate exactly with our abstraction forms. Many times, I will see documentation that a baby is irritable and jittery, which is not one of our symptoms, but as an abstractor I would automatically assume that the baby should be interpreted as hyperactive or tremors or something like that. • There’s been some difficulty surrounding what symptoms “count.” It might be something that’s more transient rather than actually related to NAS. • Abstractors have reported that it is not easy to collect infant symptoms and as a result must go through nurses’ notes, social workers’ notes, or doctors’ notes and scoring sheets. • Generally, abstracting the NAS cases is very time consuming because there are so many questions and the infants are in the hospital for a long time, so we have to look at all of those. We can’t just take day one to get all the symptoms. We have to look at all the days they are in the hospitals. It is a very time-consuming process. • NAS symptoms have proven very difficult to obtain from the medical records departments (or third-party companies hired by facilities to handle record fulfillment), as it seems to frequently be stored elsewhere in the record or chart that is not frequently checked and/or accessible.
Evidence of exposure—timing of exposure	• It is not clear if the timeline of use was in the last 4 weeks or even in the current pregnancy. • It may be documented on drug screen results but there’s no date. We don’t know if it was 4 weeks before—we just know the actual results of the drug screen. • As such, our ability to establish maternal substance use history, particularly timeline of use, is currently somewhat limited. Even in the maternal records reviewed, timeline of use may be unclear or difficult to establish. Sometimes records may note “maternal substance abuse” or “heroin addiction” under problems or history, but upon further review this may be in a note from years prior or perhaps never clarifies the time frame at all.
Case classification language	• Since the phrase “in the absence of another known cause/diagnosis” is a part of the case definition, we had added the question, “Is there another known cause or diagnosis for the clinical signs?” to our REDCap survey. On several occasions, this was marked yes even though, based on the information provided, the infant appears to have a diagnosis of NAS that’s leading to the withdrawal signs and symptoms. We’re in the process of determining why this question is causing confusion. • In these cases, because a positive history of maternal medication use is considered stronger evidence of chronic in utero substance exposure than laboratory findings, we assign the case classification type that is based on the positive history of maternal medication use, even though some types of case classification list as a criterion “no or unknown maternal laboratory results.” • The language used throughout the position statement is inconsistent. For example, they go to the effort of distinguishing confirmatory, presumptive, and supportive lab evidence, but then do not use corresponding language in the different case classifications (eg, only positive infant toxicology results for opioids, benzodiazepines, and/or barbiturates [OBBs] are considered confirmatory, but then probable type 2 and other dispositions dependent on maternal toxicology results say “confirmatory MATERNAL laboratory evidence”).

Abbreviations: CSTE, Council of State and Territorial Epidemiologists; NAS, neonatal abstinence syndrome.

^aData source: Council of State and Territorial Epidemiologists. ⁶

^bGeorgia Department of Public Health, Massachusetts Department of Public Health, Philadelphia Department of Public Health, and Tennessee Department of Health.

Challenges Abstracting Data on Withdrawal Signs From the Medical Record

Sites indicated that the process of reviewing medical records for withdrawal signs was time-consuming and methodologically burdensome (Table 2). Of the 2340 cases of NAS, 1781 (76.1%) had ≥3 signs and 219 (9.4%) had 1 or 2 signs compatible with NAS documented in the medical record (Table 3). The most common withdrawal signs were tremors (67.4% of cases), hypertonia (56.5%), and poor sleep (53.1%). The least common withdrawal signs were yawning (7.0% of cases), myoclonus (4.7%), and seizures (0.8%). Sites also reported difficulty in knowing which withdrawal signs “count” and how much interpretation of language is appropriate during the abstraction process, such as how to interpret “jittery” in the medical record.

Table 3.

Characteristics of infants with NAS (n = 2340) identified through surveillance, 4 pilot sites, ^a 2020-2021

Characteristic	No. (%)
Evidence of withdrawal
Medical diagnosis or chief complaint of NAS	1482 (63.3)
No. of withdrawal signs
≥3	1781 (76.1)
1 or 2	219 (9.4)
Withdrawal signs
Tremors	1576 (67.4)
Hypertonia	1321 (56.5)
Poor sleep	1242 (53.1)
High-pitched cry	999 (42.7)
Poor feeding	971 (41.5)
Loose stools	971 (41.5)
Tachypnea	713 (30.5)
Sneezing	662 (28.3)
Cutaneous mottling	619 (26.5)
Fever	607 (25.9)
Vomiting	585 (25.0)
Nasal congestion	582 (24.9)
Respiratory distress	563 (24.1)
Hyperactive Moro reflex	427 (18.2)
Yawning	164 (7.0)
Myoclonus	110 (4.7)
Seizures	18 (0.8)
Evidence of exposure
Positive infant toxicology
Opioids, benzodiazepines, or barbiturates	1687 (72.1)
Other substances b	230 (9.8)
Positive maternal toxicology
Opioids, benzodiazepines, or barbiturates	1622 (69.3)
Other substances b	279 (11.9)
History of substance use or prescription medication use
At <4 wk prior to delivery
Opioids, benzodiazepines, or barbiturates	921 (39.4)
Other substances b	67 (2.9)
At any time during pregnancy
Opioids, benzodiazepines, or barbiturates	1530 (65.4)
Other substances b	152 (6.5)

Abbreviations: CSTE, Council of State and Territorial Epidemiologists; NAS, neonatal abstinence syndrome.

^aGeorgia Department of Public Health, Massachusetts Department of Public Health, Philadelphia Department of Public Health, and Tennessee Department of Health.

^bExcludes cases with exposure to opioids, benzodiazepines, or barbiturates; includes but is not limited to cigarettes/tobacco, cannabis, amphetamine, fentanyl, and heroin.

Sites did not report challenges with identifying a diagnosis/chief concern of NAS in the medical record, which can also serve as evidence of withdrawal in the SSCD. Of the 2340 cases of NAS, 1482 (63.3%) had a medical diagnosis or chief concern.

Difficulty Determining the Time Frame of Prenatal Substance Exposure

Focus group participants and written reports described difficulty in establishing the timing of MSPM use in the medical record. Evidence of exposure to OBBs or other substances may be found in the medical record, but often no dates are provided to establish whether exposure occurred within 4 weeks of delivery (Table 2). Fewer than 40% of cases had an MSPM history of OBB use within 4 weeks before delivery, whereas 65.4% had a history of use at any time during pregnancy (Table 3). MSPM use at any time during pregnancy is not currently a criterion for case classification.

Identifying laboratory results to document evidence of exposure was not commonly noted as a challenge in the focus groups or written reports: 72.1% of cases had evidence of positive OBB infant toxicology and 69.3% had positive OBB maternal toxicology documented in the medical record.

Challenges Assigning Case Classifications

Focus group participants reported challenges interpreting SSCD language used to assign case classifications, particularly language that includes cases in probable and suspect classifications when there is “no or unknown laboratory evidence in the neonate” or “no or unknown maternal laboratory results” and language that excludes cases from all classifications when clinical signs can be explained by another etiology (Table 2). Some sites reported intentionally including cases with other etiologies because a case can have NAS and coexisting conditions. Among the 3 sites collecting surveillance data about other etiologies, 7.0% of cases would have been excluded if sites had implemented this element of the SSCD.

Based on site-assigned classifications, 76.0% of cases were identified as confirmed, 11.8% as probable type 1, 2.7% as probable type 2, and 5.9% as suspect type 4; <2% were identified as suspect type 1, 2, 3, or 5 (Table 4).

Table 4.

Classification of cases of neonatal abstinence syndrome by CDC and reviewers at 4 pilot sites ^a using the CSTE tier 1 standardized surveillance case definition, ^b 2020-2021 (n = 2340)

CDC classification	Classification assigned by surveillance sites, no. (%)
	Confirmed	Probable type		Suspect type					Total
		1	2	1	2	3	4	5
Confirmed	1625 (69.4)	3 (0.1)	0	1 (<0.1)	0	0	14 (0.6)	2 (0.1)	1645 (70.3)
Probable type
1	0	199 (8.5)	0	3 (0.1)	0	0	4 (0.2)	0	206 (8.8)
2	16 (0.7)	41 (1.8)	47 (2.0)	1 (<0.1)	0	0	41 (1.8)	0	146 (6.2)
Suspect type
1	0	0	0	22 (0.9)	0	19 (0.8)	0	0	41 (1.8)
2	0 (0.1)	0	0	0	0	0	0	0	0
3	79 (3.3)	1 (0.4)	16 (0.7)	6 (0.3)	0	9 (0.4)	10 (0.4)	0	121 (5.2)
4	0	0	0	0	0	0	12 (0.5)	0	12 (0.5)
5	0	0	0	0	0	0	13 (0.5)	8 (0.3)	21 (0.9)
No classification c	59 (2.5)	32 (1.4)	0	3 (0.1)	3 (0.1)	1 (<0.1)	43 (1.8)	7 (0.3)	148 (6.3)
Total	1779 (76.0)	276 (11.8)	63 (2.7)	36 (1.5)	3 (0.1)	29 (1.2)	137 (5.9)	17 (0.7)	2340 (100.0)
Agreement within classification, %	91.3	72.1	74.6	61.1	0	31.0	8.8	47.1	1922 (82.1)

Abbreviations: CDC, Centers for Disease Control and Prevention; CSTE, Council of State and Territorial Epidemiologists.

^aGeorgia Department of Public Health, Massachusetts Department of Public Health, Philadelphia Department of Public Health, and Tennessee Department of Health.

^bData source: Council of State and Territorial Epidemiologists. ⁶

^cCases that were assigned a classification by sites but for which CDC was unable to classify.

Assigned classifications agreed between CDC reviewers and site reviewers in 82.1% (n = 1922) of cases (Table 4). Of the 418 cases with conflicting classification assignments, 148 (35.4%) were assigned a classification by sites, while CDC reviewers determined that a classification could not be assigned by interpretation of the SSCD language. Among the 148 cases without a classification by CDC reviewers, 59 cases identified by sites as confirmed had positive OBB infant toxicology but did not have evidence of withdrawal (n = 12) or did not have positive OBB infant toxicology but had evidence of withdrawal (n = 47). Of the 32 site-identified probable cases that CDC could not assign a classification, none had evidence of exposure. CDC interpreted the language “no or unknown laboratory results in the neonate” in the SSCD as an exclusionary criterion; this interpretation resulted in 30 cases that could not be classified by CDC but were classified by sites as suspect cases. The remaining 27 suspect cases that could not be classified by CDC were missing sufficient evidence of exposure or evidence of withdrawal.

Discussion

This analysis found challenges in applying the tier 1 NAS SSCD across multiple jurisdictions, suggesting that varying interpretations could affect comparability of incidence estimates. These challenges were established in the focus groups and written reports and bolstered by quantitative results, which documented inconsistent application of SSCD for data collection and case classification assignments across jurisdictions. Modifications to the SSCD might be needed to promote consistent implementation across jurisdictions.

These findings identified opportunities to modify the SSCD to promote consistency and ease of implementation across jurisdictions. Removing requirements to document that exposure occurred within 4 weeks of delivery and clarifying classification language would address commonly cited site concerns. Additionally, 4 of the 5 suspect classification types accounted for <2% of overall cases, which might indicate opportunities to combine classifications. Other modifications might be identified through a comparative analysis of the current CSTE SSCD and the recently published clinical case definition for opioid withdrawal in neonates. ⁹ While each definition has a distinct purpose, appropriate alignment can increase consistency in medical record documentation and promote support among health care providers for surveillance efforts.

While focus group participants noted challenges abstracting withdrawal signs and indicated that some signs were reported infrequently, our assessment was not able to evaluate the sensitivity of specific withdrawal signs for NAS surveillance. Modifications to the withdrawal signs in the SSCD could be considered because use of different NAS scoring tools, such as Eat Sleep Console, could result in different frequencies and types of withdrawal signs recorded in the medical record. ¹⁰ Lack of documentation of withdrawal signs in medical records could result in infants being excluded from surveillance if a clinical diagnosis or chief concern is not recorded.

The standardized NAS surveillance case definition should be continually reviewed for revision to reflect the evolving landscape of NAS clinical care. For example, subsequent modifications to the SSCD may want to consider the effect of Eat Sleep Console on NAS surveillance as it becomes more widely used and the future relevance of documenting signs of NAS for surveillance. Moreover, there is growing recognition of the ethical issues surrounding laboratory-informed NAS surveillance, including variability in specimen collection and testing modality, as well as implications for universal and at-risk testing, which could lead to more frequent false-positive test results or a legal burden on families. ¹¹ Acknowledgment of these ethical concerns and justification for laboratory-informed NAS surveillance may be valuable inclusions for future revisions to the SSCD or accompanying guidance documents.

Limitations

The findings of this study were subject to several limitations. First, qualitative findings represent the perspectives of the CSTE SSCD among only the 4 participating pilot sites. Because we currently do not know how many jurisdictions outside the pilot are using the CSTE SSCD, additional perspectives on the CSTE SSCD experience may not have been captured in this evaluation. Second, 2 pilot sites relied on clinical reporting without medical record review for all NAS cases; thus, all medical record information might not have been conveyed to the health department for case classification. Third, pilot sites reported to CDC only cases that met the tier 1 NAS SSCD; thus, it was not possible to assess the characteristics of infants with an NAS clinical diagnosis/chief concern who did not meet the other SSCD criteria.

Conclusion

This study identified several opportunities to strengthen the CSTE SSCD. Promoting consistent implementation supports comparability of NAS incidence estimates across jurisdictions, evaluation of prevention efforts, and allocation of resources to support families. Further assessment, including an evaluation of the CSTE tier 2 NAS SSCD, might inform future surveillance guidance and modifications to the case definition.