Gastroschisis Trends and Ecologic Link to Opioid Prescription Rates — United States, 2006–2015

Tyiesha D. Short, MPH; Erin B. Stallings, MPH; Jennifer Isenburg, MSPH; Leslie A. O'Leary, PhD; Mahsa M. Yazdy, PhD; Michele K. Bohm, MPH; Mary Ethen, MPH; Xiaoli Chen, PhD; Tri Tran, MPH; Deborah J. Fox, MPH; Jane Fornoff, PhD; Nina Forestieri, MPH; Emily Ferrell, MPH; Glenda M. Ramirez, MPH; Jamie Kim, MPH; Jing Shi, MS; Sook Ja Cho, PhD; Kirstan Duckett, MPH; Norm Nelson, MS; Katherine Zielke, MPH; Kristen St. John, MPH; Brennan Martin, MPH; Carolina Clark, MD; My-Phuong Huynh, MPH; Colin Benusa, MPH; Jennita Reefhuis, PhD

Disclosures

Morbidity and Mortality Weekly Report. 2019;68(2):31-36.

Discussion

In the 20 states included in this report, gastroschisis prevalence increased slightly during 2011–2015 compared with that during 2006–2010. Although gastroschisis is more prevalent in infants born to mothers aged <20 years, the largest increases in prevalence occurred among mothers aged 20–24 years, 25–29 years, and ≥30 years. These findings do not entirely align with 1995–2012 data from 14 U.S. states,^[1] during which the greatest increase occurred among women aged <20 years. The current analysis includes data from more states, as well as more recent data, but there is no clear explanation for the slower rise in prevalence among the youngest group, compared with that described in the earlier analysis. In most age categories, gastroschisis prevalence was higher among non-Hispanic white mothers and Hispanic mothers than among non-Hispanic black mothers, which is consistent with previous U.S. and international reports.^[1,2]

Possible causes for the increase in gastroschisis prevalence reported both in the United States and worldwide are not well understood.^[1,2] In the ecologic analysis, gastroschisis prevalence was higher in areas with high and medium opioid prescription rates, compared with that in areas with low rates. This ecologic analysis supports the findings from a large case-control study, which suggested that self-reported prescription opioid use in the first trimester was associated with gastroschisis.^[3] There have not been any observations published on animal models for this association. In a study exploring cumulative exposures among mothers of gastroschisis patients, the effect of a combined set of stressors, including prescription opioid use, was higher among older mothers,^[4] which is consistent with the finding in the ecologic analysis that the association between opioid prescription rates and gastroschisis appeared to be more pronounced in mothers aged ≥25 years. The findings from different study designs have disparate strengths and weaknesses. The current ecologic design lacks patient-level data on exposure, but does provide information on population-level exposures and all cases of gastroschisis in each catchment area. The case-control studies have patient-level exposure data, but rely on maternal self-report and are limited to information from those mothers who voluntarily participated in the research studies. Together, these findings provide compelling evidence of the need to better understand the potential contribution of opioid exposure in the etiology of gastroschisis as well as the possible role opioids have played in the observed increases in gastroschisis.

The findings in this report are subject to at least three limitations. First, the ecologic analysis does not allow for inferring causality from the increased prevalence of gastroschisis in areas where opioid prescription rates were medium and high compared with those where opioid prescription rates were low because it could not link opioid prescriptions to individual mothers or examine timing of opioid use during pregnancy. Second, county-specific opioid prescription rate data limited to women could not be obtained, and the data did not include illicit opioid drugs, buprenorphine formulations used to treat opioid use disorder, or methadone dispensed through opioid treatment programs. However, previous research indicates that women are more likely than are men to be prescribed opioids and to report having received their opioids through prescription.^[8] Finally, this ecologic analysis did not account for county-level or patient-level confounders; it is possible that other county-level differences, in, for instance, socioeconomic status, average age at childbirth, age distribution, or differing demographics (e.g., older population with higher levels of chronic pain or use of prescription opioids), could have influenced these results. Future investigations using surveillance or case-control data will seek to examine patient-level data to account for these potential confounders as well as illicit opioid use, maternal smoking, and other polysubstance use.

The updated gastroschisis prevalence trends can be used to guide future basic science, public health, and clinical research on gastroschisis. Given that the majority of infants with gastroschisis are born to mothers aged <25 years, continued research is needed to focus on possible causal factors in the unique association between young maternal age and gastroschisis. The findings from the ecologic analysis can be used to prioritize basic science, public health, and clinical research on opioid exposure during pregnancy and its potential impact on birth defects. Having a better understanding of all possible effects of opioid use during pregnancy can help provide evidence-based information to health care providers and women about the potential risks to the developing fetus.^§

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Acknowledgments
Margaret A. Honein, PhD, National Center on Birth Defects and Developmental Disabilities, CDC; Adverse Pregnancy Outcomes Reporting System, Springfield, Illinois; Arizona Birth Defects Monitoring Program; Birth Information Network, Burlington, Vermont; Kansas Birth Defects Information System; Kentucky Birth Surveillance Registry; Louisiana Birth Defects Monitoring Network; Massachusetts Birth Defects Monitoring Program; Metropolitan Atlanta Congenital Defects Program, Atlanta, Georgia; Minnesota Birth Defects Information System; Nebraska Birth Defect Registry; New Jersey Birth Defect Registry; New York State Congenital Malformations Registry; North Carolina Birth Defects Monitoring Program; Ohio Connections for Children with Special Needs; Rhode Island Birth Defects Program; South Carolina Birth Defects Program; Tennessee Birth Defects Surveillance System; Texas Birth Defects Epidemiology and Surveillance Branch; Utah Birth Defect Network; Virginia Congenital Anomalies and Reporting Education System.

^§ https://www.pediatrics.org/cgi/doi/10.1542/peds.2018-3801.

Table. Gastroschisis cases, gastroschisis prevalence, and prevalence ratio (PR), by maternal age group and race/ethnicity for two periods — 20 U.S. states, 2006–2015*
Maternal age group (yrs),^† race/ethnicity	2006–2010		2011–2015		2006–2015		PR^¶ (95% CI)
Maternal age group (yrs),^† race/ethnicity	No. of cases	Prevalence^§ (95% CI)	No. of cases	Prevalence^§ (95% CI)	No. of cases	Prevalence^§ (95% CI)	PR^¶ (95% CI)
<20 yrs
White, non-Hispanic	461	17.1 (15.6–18.7)	420	17.2 (15.6–18.9)	881	17.1 (16.0–18.3)	1.0 (0.9–1.1)
Black, non-Hispanic	172	9.0 (7.7–10.5)	148	9.4 (8.0–11.1)	320	9.2 (8.2–10.3)	1.0 (0.8–1.3)
Hispanic	489	14.7 (13.4–16.1)	425	17.5 (15.9–19.2)	914	15.9 (14.9–16.9)	1.2 (1.0–1.4)**
A/PI or AI/AN, non-Hispanic	48	26.0 (19.2–34.5)	36	25.6 (18.0–35.5)	84	25.8 (20.6–32.0)	1.0 (0.6–1.5)
Total ^††	1,194	14.5 (13.7–15.3)	1,055	15.7 (14.8–16.7)	2,249	15.0 (14.4–15.7)	1.1 (1.0–1.2)
20–24 yrs
White, non-Hispanic	676	7.9 (7.3–8.5)	998	10.4 (9.8–11.1)	1,674	9.2 (8.8–9.7)	1.3 (1.2–1.5) **
Black, non-Hispanic	169	4.4 (3.8–5.2)	246	5.4 (4.8–6.1)	415	5.0 (4.5–5.5)	1.2 (1.0–1.5)
Hispanic	457	7.0 (6.4–7.7)	507	8.7 (8.0–9.5)	964	7.8 (7.4–8.4)	1.2 (1.1–1.4) **
A/PI or AI/AN, non-Hispanic	52	7.6 (5.7–10.0)	56	8.2 (6.2–10.7)	108	7.9 (6.5–9.6)	1.1 (0.7–1.6)
Total ^††	1,389	7.0 (6.6–7.4)	1,859	8.9 (8.5–9.3)	3,248	8.0 (7.7–8.2)	1.3 (1.2–1.4)**
25–29 yrs
White, non-Hispanic	298	2.5 (2.2–2.8)	495	3.4 (3.1–3.7)	793	3.0 (2.8–3.2)	1.4 (1.2–1.6)**
Black, non-Hispanic	51	1.6 (1.2–2.1)	89	2.3 (1.8–2.8)	140	2.0 (1.7–2.3)	1.4 (1.0–2.0)
Hispanic	153	2.5 (2.1–2.9)	188	3.2 (2.8–3.7)	341	2.8 (2.5–3.2)	1.3 (1.0–1.6)**
A/PI or AI/AN, non-Hispanic	18	1.2 (0.7–1.9)	38	2.3 (1.6–3.1)	56	1.8 (1.3–2.3)	1.9 (1.1–3.3)**
Total ^††	536	2.3 (2.1–2.5)	828	3.1 (2.9–3.4)	1,364	2.8 (2.6–2.9)	1.3 (1.2–1.5)**
≥30 yrs
White, non-Hispanic	147	0.8 (0.7–0.9)	242	1.1 (0.9–1.2)	389	0.9 (0.9–1.0)	1.3 (1.1–1.6)**
Black, non-Hispanic	28	0.8 (0.5–1.1)	46	1.0 (0.7–1.3)	74	0.9 (0.7–1.1)	1.2 (0.8–2.0)
Hispanic	51	0.7 (0.6–1.0)	83	1.1 (0.9–1.3)	134	0.9 (0.8–1.1)	1.5 (1.0–2.1)**
A/PI or AI/AN, non-Hispanic	14	0.5 (0.3–0.9)	21	0.6 (0.4–0.9)	35	0.6 (0.4–0.8)	1.2 (0.6–2.3)
Total ^††	249	0.8 (0.7–0.9)	404	1.0 (0.9–1.1)	653	0.9 (0.8–1.0)	1.3 (1.1–1.6)**
All ages
White, non-Hispanic	1,616	3.9 (3.7–4.1)	2,161	4.4 (4.2–4.6)	3,777	4.2 (4.0–4.3)	1.1 (1.1–1.2)**
Black, non-Hispanic	432	3.5 (3.1–3.8)	532	3.6 (3.3–3.9)	964	3.5 (3.3–3.8)	1.0 (0.9–1.2)
Hispanic	1,183	5.2 (4.9–5.5)	1,207	5.5 (5.2–5.9)	2,390	5.4 (5.1–5.6)	1.1 (1.0–1.2)**
A/PI or AI/AN, non-Hispanic	132	2.6 (2.2–3.1)	152	2.6 (2.2–3.0)	284	2.6 (2.3–2.9)	1.0 (0.8–1.2)
Total ^††	3,489	4.2 (4.0–4.3)	4,166	4.5 (4.3–4.6)	7,655	4.3 (4.2–4.4)	1.1 (1.0–1.1)**

Abbreviations: A/PI = Asian/Pacific Islander; AI/AN = American Indian/Alaska Native; CI = confidence interval.
* States contributing to the table: Arizona, CDC/Georgia (Metropolitan Atlanta Congenital Defects Program), Illinois, Kansas, Kentucky, Louisiana (2010–2015), Massachusetts, Minnesota, Nebraska, New Jersey, New York, North Carolina, Ohio (2010–2015), Rhode Island, South Carolina (2010–2015), Tennessee (2010–2015), Texas, Utah, Vermont (2009–2015), and Virginia. Data were provided from 2006 to 2015 unless otherwise noted.
^† Cases missing information on maternal age are not included in this table.
^§ Prevalence per 10,000 live births.
^¶ Unrounded prevalence for 2011–2015 divided by the unrounded prevalence for 2006–2010.
** Denotes a statistically significant confidence interval.
^†† Total includes non-Hispanic white, non-Hispanic black, Hispanic, non-Hispanic A/PI, non-Hispanic AI/AN, and other/unknown maternal race/ethnicity.