Lactogenesis and breastfeeding after immediate vs delayed birth-hospitalization insertion of etonogestrel contraceptive implant: a noninferiority trial.

BACKGROUND: Initiating a progestin-based contraceptive before the drop in progesterone required to start lactogenesis stage II could theoretically affect lactation. Previous studies have shown that initiating progestin-based contraception in the postnatal period before birth-hospitalization discharge has no detrimental effects on breastfeeding initiation or continuation compared with outpatient interval initiation. However, there are currently no breastfeeding data on the impact of initiating the etonogestrel contraceptive implant in the early postnatal period immediately in the delivery room. OBJECTIVE: This study examined the effect of delivery room vs delayed birth-hospitalization contraceptive etonogestrel implant insertion on breastfeeding outcomes. STUDY DESIGN: This was a noninferiority randomized controlled trial to determine if time to lactogenesis stage II (initiation of copious milk secretion) differs by timing of etonogestrel implant insertion during the birth-hospitalization. We randomly assigned pregnant people to insertion at 0 to 2 hours (delivery room) vs 24 to 48 hours (delayed) postdelivery. Participants intended to breastfeed, desired a contraceptive implant for postpartum contraception, were fluent in English or Spanish, and had no allergy or contraindication to the etonogestrel implant. We collected demographic information and breastfeeding intentions at enrollment. Onset of lactogenesis stage II was assessed daily using a validated tool. The noninferiority margin for the mean difference in time to lactogenesis stage II was defined as 12 hours in a per-protocol analysis. Additional electronic surveys collected data on breastfeeding and contraceptive continuation at 2 and 4 weeks, and 3, 6, and 12 months. RESULTS: We enrolled and randomized 95 participants; 77 participants were included in the modified intention-to-treat analysis (n=38 in the delivery room group and n=39 in the delayed group) after excluding 18 because of withdrawing consent, changing contraceptive or breastfeeding plans, or failing to provide primary outcome data. A total of 69 participants were included in the as-treated analysis (n=35 delivery room, n=34 delayed); 8 participants who received the etonogestrel implant outside the protocol windows were excluded, and 2 participants from the delivery room group received the etonogestrel implant at 24 to 48 hours and were analyzed with the delayed group. Participants were similar between groups in age, gestational age, and previous breastfeeding experience. Delivery room insertion was noninferior to delayed birth-hospitalization insertion in time to lactogenesis stage II (delivery room [mean±standard deviation], 65±25 hours; delayed, 73±61 hours; mean difference, -9 hours; 95% confidence interval, -27 to 10). Onset of lactogenesis stage II by postpartum day 3 was not significantly different between the groups. Lactation failure occurred in 5.5% (n=2) participants in the delayed group. Ongoing breastfeeding rates did not differ between the groups, with decreasing rates of any/exclusive breastfeeding over the first postpartum year. Most people continued to use the implant at 12 months, which did not differ by group. CONCLUSION: Delivery room insertion of the contraceptive etonogestrel implant does not delay the onset of lactogenesis when compared with initiation later in the birth-hospitalization and therefore should be offered routinely as part of person-centered postpartum contraceptive counseling, regardless of breastfeeding intentions.

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings.

BACKGROUND: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. METHODS: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. RESULTS: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. CONCLUSION: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

Review of Automated Insulin Delivery Systems for Type 1 Diabetes and Associated Time in Range Outcomes.

Automated insulin delivery (AID) systems play an important role in the management of type 1 diabetes mellitus (T1DM). These systems include three components: a continuous glucose monitor (CGM), an insulin pump and an algorithm that adjusts the pump based on the CGM sensor glucose readings. They are not fully automated and still require the user to administer bolus insulin doses for food. Some AID systems have automatic correction boluses, while others only have automatic basal or background insulin adjustments. As CGM has become more accurate and the technology has evolved, AID systems have demonstrated improved glycaemic outcomes. The clinical evaluation of AID systems in randomized controlled trials and real-world studies have shown their utility in helping glycaemic management. In this review, we compare AID systems that are commercially available in the US and summarize the literature, with a special focus on time in range in T1DM. The review also discusses new AID systems on the horizon and explores considerations for personalized care.

Variable levels of drift in tunicate cardiopharyngeal gene regulatory elements.

BACKGROUND: Mutations in gene regulatory networks often lead to genetic divergence without impacting gene expression or developmental patterning. The rules governing this process of developmental systems drift, including the variable impact of selective constraints on different nodes in a gene regulatory network, remain poorly delineated. RESULTS: Here we examine developmental systems drift within the cardiopharyngeal gene regulatory networks of two tunicate species, Corella inflata and Ciona robusta. Cross-species analysis of regulatory elements suggests that trans-regulatory architecture is largely conserved between these highly divergent species. In contrast, cis-regulatory elements within this network exhibit distinct levels of conservation. In particular, while most of the regulatory elements we analyzed showed extensive rearrangements of functional binding sites, the enhancer for the cardiopharyngeal transcription factor FoxF is remarkably well-conserved. Even minor alterations in spacing between binding sites lead to loss of FoxF enhancer function, suggesting that bound trans-factors form position-dependent complexes. CONCLUSIONS: Our findings reveal heterogeneous levels of divergence across cardiopharyngeal cis-regulatory elements. These distinct levels of divergence presumably reflect constraints that are not clearly associated with gene function or position within the regulatory network. Thus, levels of cis-regulatory divergence or drift appear to be governed by distinct structural constraints that will be difficult to predict based on network architecture.