Caesarean delivery and the risk of atopic dermatitis in children.

BACKGROUND: Caesarean delivery (C-section) may disrupt maternal-infant microbial transfer and alter immune system development and subsequent risk for atopic dermatitis. OBJECTIVE: Investigate the association between C-section and atopic dermatitis by age four and examine potential sources of bias in the relationship in a large cohort study. METHODS: Maternal and child information was collected through Kaiser Permanente Northern California's (KPNC) integrated healthcare system. Data sources included electronic medical records, pharmacy databases, state birth records, and prospectively collected breastfeeding surveys. Children were eligible if they were born in a KPNC or contracting hospital between 2005 and 2014 and had continuous enrolment in the KPNC system for at least four years (n = 173 105). Modified Poisson regression with robust variance estimation was used to estimate the association between C-section and atopic dermatitis overall and when stratified by demographic and labour and delivery characteristics. RESULTS: Although unadjusted analyses showed a positive association between C-section and atopic dermatitis [RR(95%CI): 1.06(1.03, 1.10)], this effect was attenuated towards the null after adjustment [aRR(95%CI): 1.02(0.99, 1.05)]. In stratified analyses, there was evidence that C-section increased atopic dermatitis risk among certain subgroups (eg firstborns, overweight/obese pre-pregnancy BMI), but associations were weak. C-section delivery conditions indicative of the least exposure to maternal microbiome (ie no labour, short interval between membrane rupture and delivery) showed no evidence of association with atopic dermatitis. Estimated associations were not strongly influenced by intrapartum antibiotics, breastfeeding, missing data, or familial factors. CONCLUSION: Caesarean delivery was not associated with atopic dermatitis by age four in this large US cohort. This association did not appear to be biased by intrapartum antibiotics, breastfeeding behaviour, C-section indication, missing covariates, or familial factors.

Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration.

BACKGROUND: The subdermal contraceptive implant and the 52-mg levonorgestrel intrauterine device are currently Food and Drug Administration approved for 3 and 5 years of use, respectively. Limited available data suggested both of these methods are effective beyond that time. Demonstration of prolonged effectiveness will improve the cost-effectiveness of the device, and potentially patient continuation and satisfaction. OBJECTIVE: We sought to evaluate the effectiveness of the contraceptive implant and the 52-mg hormonal intrauterine device in women using the method for 2 years beyond the current Food and Drug Administration-approved duration. STUDY DESIGN: We initiated this ongoing prospective cohort study in January 2012. We are enrolling women using the contraceptive implant or 52-mg levonorgestrel intrauterine device for a minimum of 3 and 5 years, respectively (started intrauterine device in ≥2007 or implant in ≥2009). Demographic and reproductive health histories, as well as objective body mass index, were collected. Implant users were offered periodic venipuncture for analysis of serum etonogestrel levels. The primary outcome, unintended pregnancy rate, was calculated per 100 woman-years. We analyzed baseline demographic characteristics using χ2 test and Fisher exact test, and compared serum etonogestrel levels stratified by body mass index using the Kruskal-Wallis test. RESULTS: Implant users (n = 291) have contributed 444.0 woman-years of follow-up. There have been no documented pregnancies in implant users during the 2 years of postexpiration follow-up. Calculated failure rates in the fourth and fifth years for the implant are calculated as 0 (1-sided 97.5% confidence interval, 0-1.48) per 100 woman-years at 4 years and 0 (1-sided 97.5% confidence interval, 0-2.65) per 100 woman-years at 5 years. Among 496 levonorgestrel intrauterine device users, 696.9 woman-years of follow-up have been completed. Two pregnancies have been reported. The failure rate in the sixth year of use of the levonorgestrel intrauterine device is calculated as 0.25 (95% confidence interval, 0.04-1.42) per 100 woman-years; failure rate during the seventh year is 0.43 (95% confidence interval, 0.08-2.39) per 100 woman-years. Among implant users with serum etonogestrel results, the median etonogestrel level was 207.7 pg/mL (range 63.8-802.6 pg/mL) at the time of method expiration, 166.1 pg/mL (range 67.9 25.0-470.5 pg/mL) at the end of the fourth year, and 153.0 pg/mL (range 72.1-538.8 pg/mL) at the end of the fifth year. Median etonogestrel levels were compared by body mass index at each time point and a statistical difference was noted at the end of 4 years of use with overweight women having the highest serum etonogestrel (195.9; range 25.0-450.5 pg/mL) when compared to normal (178.9; range 87.0-463.7 pg/mL) and obese (137.9; range 66.0-470.5 pg/mL) women (P = .04). CONCLUSION: This study indicates that the contraceptive implant and 52-mg hormonal intrauterine device continue to be highly effective for at least 2 additional years of use. Serum etonogestrel evaluation demonstrates median levels remain above the ovulation threshold of 90 pg/mL for women in all body mass index classes.

Use of the etonogestrel implant and levonorgestrel intrauterine device beyond the U.S. Food and Drug Administration-approved duration.

OBJECTIVE: To evaluate the effectiveness of the contraceptive implant and the 52-mg hormonal intrauterine device (IUD) in women using the method beyond the current U.S. Food and Drug Administration (FDA)-approved duration of 3 and 5 years, respectively. METHODS: Women willing to continue using their implant or 52-mg levonorgestrel IUD beyond the FDA-approved duration were followed prospectively for contraceptive effectiveness. Unintended pregnancy rate per 100 women-years was calculated. Implant users are offered periodic venipuncture for analysis of serum etonogestrel levels. The Kruskal-Wallis test was used to compare the etonogestrel levels across body mass index (BMI) groups. RESULTS: Implant users (n=237) have contributed 229.4 women-years of follow-up, with 123 using the etonogestrel implant for 4 years and 34 using it for 5 years. Zero pregnancies have been documented, for a failure rate of 0 (one-sided 97.5% confidence interval [CI] 0-1.61) per 100 women-years. Among 263 levonorgestrel IUD users, 197.7 women-years of follow-up have been completed. One pregnancy was confirmed, for a failure rate of 0.51 (95% CI 0.01-2.82) per 100 women-years. Among implant users with serum etonogestrel results, the median and range of etonogestrel level at 3 years of use was 188.8 pg/mL (range 63.8-802.6 pg/mL) and 177.0 pg/mL (67.9-470.5 pg/mL) at 4 years of use. Etonogestrel levels did not differ by BMI at either time point (3 years: P=.79; 4 years: P=.47). CONCLUSION: Preliminary findings indicate the contraceptive implant and 52-mg hormonal IUD continue to be highly effective for an additional year beyond the FDA-approved 3 and 5 years. Serum etonogestrel levels indicate the implant contains adequate hormone for ovulation suppression at the end of both 3 and 4 years of use. LEVEL OF EVIDENCE: II.

Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in Sprague Dawley rat.

STUDY OBJECTIVES: Dexmedetomidine is used clinically to induce states of sedation that have been described as homologous to nonrapid eye movement (NREM) sleep. A better understanding of the similarities and differences between NREM sleep and dexmedetomidine-induced sedation is essential for efforts to clarify the relationship between these two states. This study tested the hypothesis that dexmedetomidine-induced sedation is homologous to sleep. DESIGN: This study used between-groups and within-groups designs. SETTING: University of Michigan. PARTICIPANTS: Adult male Sprague Dawley rats (n = 40). INTERVENTIONS: Independent variables were administration of dexmedetomidine and saline or Ringer's solution (control). Dependent variables included time spent in states of wakefulness, sleep, and sedation, electroencephalographic (EEG) power, adenosine levels in the substantia innominata (SI), and activation of pCREB and c-Fos in sleep related forebrain regions. MEASUREMENTS AND RESULTS: Dexmedetomidine significantly decreased time spent in wakefulness (-49%), increased duration of sedation (1995%), increased EEG delta power (546%), and eliminated the rapid eye movement (REM) phase of sleep for 16 h. Sedation was followed by a rebound increase in NREM and REM sleep. Systemically administered dexmedetomidine significantly decreased (-39%) SI adenosine levels. Dialysis delivery of dexmedetomidine into SI did not decrease adenosine level. Systemic delivery of dexmedetomidine did not alter c-Fos or pCREB expression in the horizontal diagonal band, or ventrolateral, median, and medial preoptic areas of the hypothalamus. CONCLUSIONS: Dexmedetomidine significantly altered normal sleep phenotypes, and the dexmedetomidine-induced state did not compensate for sleep need. Thus, in the Sprague Dawley rat, dexmedetomidine-induced sedation is characterized by behavioral, electrographic, and immunohistochemical phenotypes that are distinctly different from similar measures obtained during sleep.