Optimizing health and management of medical conditions before conception can improve the likelihood of becoming pregnant and of an uncomplicated pregnancy. This article reviews best practices in preconception medical care for cisgender pregnancy-capable women desiring conception to optimize their fertility, improve their perinatal well-being, and decrease the likelihood of pregnancy complications. Given that almost half of all pregnancies in the United States are unintended or mistimed, internal medicine physicians are well positioned to proactively provide reproductive counseling and care.
BACKGROUND Doxycycline is commonly prescribed to reproductive-aged women, but evidence about safety during pregnancy is limited. OBJECTIVE To evaluate the risk for pregnancy loss after doxycycline exposure in the first trimester. DESIGN Retrospective active-comparator cohort study. SETTING Merative MarketScan commercial (2005-2021) and Medicaid (1999-2019) claims data. PARTICIPANTS Pregnancies ending in loss or live birth among women aged 12 to 55 years. INTERVENTION 3 cohorts of pregnancies with first-trimester oral doxycycline or comparator antibiotic prescription fills and concomitant diagnoses of respiratory tract infection (RTI) or acne. MEASUREMENTS Pregnancy loss was evaluated using validated algorithms. Doxycycline-exposed pregnancies were matched on propensity score and gestational age to comparator pregnancies (exposed to amoxicillin or a macrolide for RTI or topical clindamycin for acne). Adjusted risk differences and adjusted risk ratios (aRRs) were estimated via binomial and modified Poisson regression separately for each database and comparison. RESULTS The study included 218 234 pregnant participants with RTI (110 254 in MarketScan, 107 980 in Medicaid) and 6636 with acne (4719 in MarketScan, 1917 in Medicaid). Among those with RTI, doxycycline use was associated with an increased risk for pregnancy loss compared with amoxicillin use (MarketScan aRR, 1.54 [95% CI, 1.41 to 1.68]; Medicaid aRR, 1.40 [CI, 1.28 to 1.53]). Results were similar for the comparison with macrolides (MarketScan aRR, 1.39 [CI, 1.28 to 1.51]; Medicaid aRR, 1.36 [CI, 1.25 to 1.48]). Among patients with acne, the comparison with topical clindamycin was statistically significant in MarketScan (aRR, 1.49 [CI, 1.26 to 1.76]) but not Medicaid (aRR, 1.03 [CI, 0.80 to 1.33]). Among cohorts with statistically significant aRRs, risk differences ranged between 7 and 11 percentage points. LIMITATION Residual confounding and exposure or outcome misclassification are possible, and congenital malformations were not evaluated. CONCLUSION Doxycycline use for RTI or acne during early pregnancy was associated with an increased risk for pregnancy loss. Clinicians may use this information to weigh risks and benefits when prescribing doxycycline to reproductive-aged women. PRIMARY FUNDING SOURCE Centers for Disease Control and Prevention.
Serine is a critical nutrient for cancer cell proliferation due to its numerous downstream biosynthetic functions. Given the ongoing clinical efforts to utilize dietary serine starvation as a potential therapy for serine auxotrophic tumors, it is important to understand how cancer cells respond to serine starvation. In this study, we demonstrated that serine starvation induces dramatic changes in mRNA splicing. These effects are due, in part, to reduced translation of serine-rich proteins, including the serine/arginine-rich splicing factor (SRSF) proteins that are known regulators of mRNA splicing. Indeed, translation of SRSF6 was reduced upon serine starvation in serine auxotrophic cancer cells and contributes to the RNA splicing changes seen upon serine deprivation. Furthermore, reduced SRSF6 affected DNA damage response and cell survival in the absence of exogenous serine, and modulators of RNA splicing combined with dietary serine starvation to inhibit tumor growth. Collectively, this work describes a fundamental role for serine in supporting mRNA splicing, which may have implications in the clinical efforts to bring dietary serine starvation to the clinic.Significance: Serine starvation induces changes in mRNA splicing by inhibiting translation of serine-rich proteins like SRSF6, which impacts the DNA damage response and could affect how cancer cells respond to chemotherapy.
