Background: The prevalence of opioid use disorder has increased across the United States, but the rural population of Appalachia has been disproportionately impacted. Concurrently, the slow, but steady progress in the legalization of marijuana may be affecting perception of marijuana use in pregnancy. However, marijuana use in pregnancy has been associated with adverse perinatal outcomes. Concomitant use of opioids and marijuana in pregnancy has not been evaluated. Objective: The primary aim of the study was to evaluate the association between confirmed marijuana use in late pregnancy and preterm birth in opioid-exposed pregnancies. Methodology: A retrospective chart review was conducted that included all births from July 2011 to June 2016 from 6 delivery hospitals in South-Central Appalachia. Out of 18,732 births, 2368 singleton pregnancies indicated opioid use and met remaining inclusion criteria, with 108 of these mothers testing positive for marijuana at delivery. Independent sample t-test and Chi-Square analyses compared marijuana and non-marijuana exposed groups on maternal and neonatal outcomes. Regression analyses controlled for confounding variables in predicting neonatal abstinence syndrome (NAS), NICU admission, preterm birth, small for gestational age, and low birth weight outcomes as shown in Table 1. Results: Neonates born to marijuana-positive women in opioid-exposed pregnancy were more likely to be born preterm, small for gestational age, have low birth weight, and be admitted to NICU. After statistically controlling for parity, marital status, tobacco and benzodiazepine use, preterm birth and low birth weight remained statistically significant with aOR of 2.35 (1.30–4.24) and 2.01 (1.18–3.44), respectively. Conclusions: Maternal use of marijuana in any opioid-exposed pregnancy may increase risk of preterm birth and low-birth weight infants. Prospective studies need to examine the dose and timing of marijuana and opioid use in pregnancy to better delineate perinatal effects. Nonetheless, pregnant women using opioids, including recommended medication assisted treatment for opioid use disorder, should be educated about the risks of concurrent marijuana use during pregnancy and may need to be counseled to abstain from marijuana use during pregnancy for an optimal outcome.

Preterm birth (PTB) results in over 15 million early births annually and is the leading cause of neonatal deaths. There are no clinical methods currently available to evaluate risk of PTB at early stages in pregnancy; thus, a rapid diagnostic to analyze PTB risk would be beneficial. Microfluidic immunoaffinity extraction is a promising platform for preparing complex samples, such as maternal serum with PTB risk biomarkers. 3D printed microfluidic devices have advantages over conventional microfluidic systems including simple fabrication and potential for iterative optimization to improve designs. In this work, I developed immunoaffinity monoliths in 3D printed microfluidic devices modified with antibodies to enrich PTB biomarkers from human blood serum. I retained and eluted a peptide PTB biomarker in both buffer and blood serum using an immunoaffinity column. An additional three PTB biomarkers were also successfully extracted either from buffer or blood serum on single-antibody columns. Both polyclonal and monoclonal antibodies to PTB biomarkers were characterized by dot blots, biolayer interferometry, and surface plasmon resonance to determine their specificity and dissociation constants. I created multiplexed immunoaffinity columns to simultaneously enrich three PTB biomarkers from depleted human blood serum in a single extraction. This is the first demonstration of multiplexed immunoaffinity columns for PTB biomarkers in a 3D printed microfluidic device. My work is a key step towards the future development of 3D printed microfluidic devices for rapid PTB testing.