Birth outcomes following in utero co-exposure to tobacco and marijuana.

BACKGROUND: With recent changes in tobacco and marijuana use patterns, it becomes crucial to understand how the prenatal co-use of these substances impacts birth outcomes. The goal of this study was to examine the risk of adverse birth outcomes among infants born to women who used tobacco and marijuana concurrently throughout pregnancy compared to infants of women who used tobacco alone. METHODS: This study involved a retrospective chart review of pregnant women identified via self-report or biochemical testing who used tobacco products alone (N = 71) or tobacco and marijuana simultaneously (N = 127) at any point throughout pregnancy. Differences in birth outcomes between these groups, including APGAR (appearance, pulse, grimace, activity, and respiration) scores, respiratory distress, neonatal intensive care unit admission, intrauterine growth restriction, birth weight, birth length, head circumference, gestational age, and length of hospital stay, were analyzed using linear regression and odds ratio analysis. RESULTS: There were no significant differences in outcomes for infants of women who used tobacco and marijuana compared to infants of women who used tobacco alone during pregnancy. Rates of adverse birth outcomes were high among women who used tobacco compared to what would be expected in unexposed pregnancies. CONCLUSIONS: Tobacco and marijuana co-use during pregnancy was not associated with an additional risk of adverse birth outcomes compared to tobacco use alone. Women should be educated on potential risks of marijuana, and especially, tobacco use during pregnancy. These results will inform clinical recommendations for pregnant women using tobacco and marijuana, aiming to decrease preventable adverse outcomes for patients and infants.

In utero effects of opioids on fetal growth.

BACKGROUND: Studies indicate antenatal opioid use is associated with birth size deficits, as evidenced by reductions in birth weight and head circumference. However, there remains a limited understanding of how early this growth restriction occurs, and what specific parameters are affected. This novel study evaluated global and specific growth deficits associated with prenatal opioid exposure between 18-22 weeks' gestation as assessed during anatomy ultrasounds. METHODS: Pregnant women who completed an anatomy ultrasound were identified via electronic medical records from a large academic obstetric practice. The study group used opioids, with tobacco and/or marijuana use permitted (n = 41). The control group could have used tobacco and/or marijuana, but not opioids (n = 308). Neither group had alcohol or other drug exposure. Records were reviewed for medical history and ultrasound size parameters, coded as percentiles for gestational age. RESULTS: Demographics and medical histories were compared with several significant differences noted. After controlling for these differences, significant (p < 0.05) growth deficits were identified in opioid-exposed fetuses. Specifically, reductions >10 percentile points were observed in head circumference, biparietal diameter, and humerus length for opioid-exposed fetuses compared to controls. Additionally, intrauterine growth restriction (IUGR) was diagnosed five times more often. Femur length was significantly reduced in opioid-exposed fetuses prior to adjustment for confounding (p = .016), but this reduction was not significant (p = .072) after controlling for background differences. Estimated fetal weight (p = .274) and abdominal circumference (p = .633) were not significantly different between exposure groups. CONCLUSION: Fetal opioid exposure predicted various bone growth deficits during routine anatomy ultrasound, indicating the effects of opioid exposure on size deficits may be evident as early as 18-22 weeks' gestation. These findings may also suggest that in utero opioid exposure negatively impacts bone growth specifically rather than weight or fat/muscle mass. Additional studies with larger sample sizes may also reveal significantly reduced femur length, further supporting a negative impact on bone growth. Future studies evaluating bone health and immune function in children after antenatal opioid exposure may help clarify this specific effect of opioids on bone development.

Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood.

In genetic and pharmacological models of neurodevelopmental disorders, and human data, neural activity is altered within the developing neocortical network. This commonality begs the question of whether early enhancement in excitation might be a common driver, across etiologies, of characteristic behaviors. We tested this concept by chemogenetically driving cortical pyramidal neurons during postnatal days 4-14. Hyperexcitation of Emx1-, but not dopamine transporter-, parvalbumin-, or Dlx5/6-expressing neurons, led to decreased social interaction and increased grooming activity in adult animals. In vivo optogenetic interrogation in adults revealed decreased baseline but increased stimulus-evoked firing rates of pyramidal neurons and impaired recruitment of inhibitory neurons. Slice recordings in adults from prefrontal cortex layer 5 pyramidal neurons revealed decreased intrinsic excitability and increased synaptic E/I ratio. Together these results support the prediction that enhanced pyramidal firing during development, in otherwise normal cortex, can selectively drive altered adult circuit function and maladaptive changes in behavior.