The association between sleep-disordered breathing and maternal endothelial and metabolic markers in pregnancies complicated by obesity.

STUDY OBJECTIVES: To evaluate the impact of sleep-disordered breathing (SDB) on vascular, angiogenic and metabolic analytes in pregnancy. METHODS: Participants with a body mass index ≥30 kg/m2 underwent polysomnography at 14-20 weeks gestation (visit 1). Participants with SDB (defined as an apnea-hypopnea index ≥5 events/h) were then enrolled in a separate trial. SDB-negative participants returned for a polysomnogram at 28-31 weeks (visit 2) and were recategorized as persistent-negative SDB or new-onset SDB. Mean arterial blood pressure, mean uterine artery Doppler pulsatility index, endoglin, soluble Feline McDonough Sarcoma-like tyrosine kinase 1, placental growth factor, and the homeostatic model assessment for insulin resistance were measured after each visit. Our primary outcome was a composite of uterine artery Doppler pulsatility index, soluble FMS-like tyrosine kinase 1/placental growth factor ratio, and homeostatic model assessment for insulin resistance. For secondary analyses, each outcome variable was analyzed independently. RESULTS: A total of 242 and 130 participants completed visit 1 and visit 2, respectively. Newly diagnosed SDB was present in 37% of individuals at visit 1 and 31% of individuals at visit 2. No significant differences in our composite outcome vector were observed in individuals with and without SDB at either visit. In our secondary analysis, mean arterial blood pressure (88.7 ± 7.3 mm Hg vs 85.4 ± 7.1 mm Hg, P = .04) and fasting glucose (92.4 ± 15.2 mg/dL vs 86.6 ± 11.5 mg/dL, P = .05) were higher in participants with early pregnancy SDB. These associations were not observed for new-onset SDB. No associations were observed between uterine artery Doppler pulsatility index and angiogenic markers and SDB in pregnancy. CONCLUSIONS: SDB in early pregnancy was not associated with our composite primary outcome but was associated with higher mean arterial blood pressure and fasting glucose. The pathophysiologic changes that occur in pregnant individuals with SDB and how they lead to an increased risk of preeclampsia and gestational diabetes remain poorly understood. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Sleep Disordered Breathing, Obesity and Pregnancy Study (SOAP); URL: https://clinicaltrials.gov/ct2/show/NCT02086448; Identifier: NCT02086448. CITATION: Onslow ML, Wolsk J, Wisniewski S, et al. The association between sleep-disordered breathing and maternal endothelial and metabolic markers in pregnancies complicated by obesity. J Clin Sleep Med. 2023;19(1):97-109.

Uterocervical Angle Measurement Improves Prediction of Preterm Birth in Twin Gestation.

OBJECTIVE: Twin pregnancies are associated with an increased risk of spontaneous preterm birth. Our objective was to compare the performance of uterocervical angle to cervical length as predictors of spontaneous preterm birth in this population. METHODS: We conducted a retrospective cohort study of twin gestations at a single center from May 2008 to 2016 who received a transvaginal ultrasound for the evaluation of the cervix between 16 0/7 and 23 0/7 weeks. The primary outcome was prediction of preterm birth <28 and <32 weeks by uterocervical angle and cervical length. RESULTS: Among 259 women with twin gestation, the mean gestational age at birth was 34.83 ± 3.48 weeks. Receiver operator characteristic curves demonstrated optimal prediction of spontaneous preterm birth prior to 32 weeks at a uterocervical angle >110° (80% sensitivity, 82% specificity) [odds ratio (OR), 15.7 (95% confidence interval (CI), 7.2-34.4)] versus cervical length <20 mm (53% sensitivity, 85% specificity; p < 0.001, OR, 6.4 [95% CI, 2.3-17.8]) and similarly, prior to 28 weeks at a uterocervical angle >114° (OR, 24.3 [95% CI, 6.7-88.5]) compared with cervical length <20 mm (OR, 11.4 [95% CI, 3.5-36.7]). CONCLUSION: Uterocervical angles >110° performed better than cervical length for the prediction of spontaneous preterm birth in twin gestations.

Fundamentals of Clinical Pharmacology With Application for Pregnant Women.

Medication use is common in pregnancy, yet for most medications the optimal formulation and dosage have not been described specifically for pregnant women. Often, adverse effects are only discovered anecdotally or after extensive off-label use occurs. Since pharmacologic research that includes pregnant women is sparse and animal studies are often not applicable to the human fetus, providers must use knowledge of drug behavior and normal physiologic changes of pregnancy to personalize treatment for pregnant women. In this review, we present an overview of the basic concepts of clinical pharmacology: pharmacokinetics, pharmacodynamics, and pharmacogenomics. The normal physiologic changes of pregnancy are presented as a framework to understand alterations in drug behavior. A clinical vignette that addresses 4 pregnancy scenarios involving medications-preterm birth, vaccination, herpes simplex virus infection, and codeine toxicity-is provided to illustrate application of core clinical pharmacologic concepts. Discussion of relevant literature illustrates the challenges of offering individualized pharmacologic therapy in pregnancy.

Principles of Anti-infective Dosing in Pregnancy.

PURPOSE: Anti-infectives are among the most commonly prescribed medications in pregnancy. However, detailed information on the pharmacokinetics and pharmacodynamics of these medications in pregnancy is limited, leading to uncertainty among clinicians regarding the tolerability and efficacy of treatments. The purposes of this review were to highlight key physiologic changes during pregnancy that influence drug behavior, and to discuss areas of active research related to anti-infective drugs in pregnancy. METHODS: A review of literature in PubMed was performed for topics related to physiologic changes of pregnancy, postcesarean surgical site infections, vaccines in pregnancy, and intrauterine infections. The literature was reviewed and pertinent sources were utilized for this article. FINDINGS: Physiologic changes during pregnancy may impact drug disposition and efficacy. Cefazolin regimens are the current prophylactic treatment of choice for postcesarean surgical site infections. Vaccines are provided in pregnancy for both maternal and neonatal benefit. Broad-spectrum antibiotics continue to be used as first-line therapy for intrauterine infections. IMPLICATIONS: Continued efforts to broaden the knowledge base on anti-infective drug behavior in pregnancy will result in increased therapeutic options for this population.

Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.

We used the Immunochip array to analyze 2,816 individuals with juvenile idiopathic arthritis (JIA), comprising the most common subtypes (oligoarticular and rheumatoid factor-negative polyarticular JIA), and 13,056 controls. We confirmed association of 3 known JIA risk loci (the human leukocyte antigen (HLA) region, PTPN22 and PTPN2) and identified 14 loci reaching genome-wide significance (P < 5 × 10(-8)) for the first time. Eleven additional new regions showed suggestive evidence of association with JIA (P < 1 × 10(-6)). Dense mapping of loci along with bioinformatics analysis refined the associations to one gene in each of eight regions, highlighting crucial pathways, including the interleukin (IL)-2 pathway, in JIA disease pathogenesis. The entire Immunochip content, the HLA region and the top 27 loci (P < 1 × 10(-6)) explain an estimated 18, 13 and 6% of the risk of JIA, respectively. In summary, this is the largest collection of JIA cases investigated so far and provides new insight into the genetic basis of this childhood autoimmune disease.