Pharmacogenetics and individualizing drug treatment during pregnancy

Pharmacogenetics as a tool to aid clinicians implement individualized pharmacotherapy is utilized in some areas of medicine. Pharmacogenetics in pregnancy is still a developing field. However, there are several areas of obstetric therapeutics where data are emerging that give glimpses into future therapeutic possibilities. These include opioid pain management, antihypertensive therapy, antidepressant medications, preterm labor tocolytics, antenatal corticosteroids and drugs for nausea and vomiting of pregnancy, to name a few. More data are needed to populate the therapeutic models and to truly determine if pharmacogenetics will aid in individualizing pharmacotherapy in pregnancy. The objective of this review is to summarize current data and highlight research needs

Incentives for increasing prenatal care use by women in order to improve maternal and neonatal outcomes

BACKGROUND: Prenatal care is recommended during pregnancy as a method to improve neonatal and maternal outcomes. Improving the use of prenatal care is important, particularly for women at moderate to high risk of adverse outcomes. Incentives are sometimes utilized to encourage women to attend prenatal care visits. OBJECTIVES: To determine whether incentives are an effective tool to increase utilization of timely prenatal care among women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015) and the reference lists of all retrieved studies. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-RCTs, and cluster-RCTs that utilized direct incentives to pregnant women explicitly linked to initiation and frequency of prenatal care were included. Incentives could include cash, vouchers, coupons or products not generally offered to women as a standard of prenatal care. Comparisons were to no incentives and to incentives not linked directly to utilization of care. We also planned to compare different types of interventions, i.e. monetary versus products or services. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and methodological quality. Two review authors independently extracted data. Data were checked for accuracy. MAIN RESULTS: We identified 11 studies (19 reports), six of which we excluded. Five studies, involving 11,935 pregnancies were included, but only 1893 pregnancies contributed data regarding our specified outcomes. Incentives in the studies included cash, gift card, baby carrier, baby blanket or taxicab voucher and were compared with no incentives. Meta-analysis was performed for only one outcome 'Return for postpartum care' and this outcome was not pre-specified in our protocol. Other analyses were restricted to data from single studies.Trials were at a moderate risk of bias overall. Randomization and allocation were adequate and risk of selection bias was low in three studies and unclear in two studies. None of the studies were blinded to the participants. Blinding of outcome assessors was adequate in one study, but was limited or not described in the remaining four studies. Risk of attrition was deemed to be low in all studies that contributed data to the review. Two of the studies reported or analyzed data in a manner that was not consistent with the predetermined protocol and thus were deemed to be at high risk. The other three studies were low risk for reporting bias. The largest two of the five studies comprising the majority of participants took place in rural, low-income, homogenously Hispanic communities in Central America. This setting introduces a number of confounding factors that may affect generalizability of these findings to ethnically and economically diverse urban communities in developed countries.The five included studies of incentive programs did not report any of this review's primary outcomes: preterm birth, small-for-gestational age, or perinatal death.In terms of this review's secondary outcomes, pregnant women receiving incentives were no more likely to initiate prenatal care (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.78 to 1.38, one study, 104 pregnancies). Pregnant women receiving incentives were more likely to attend prenatal visits on a frequent basis (RR 1.18, 95% CI 1.01 to 1.38, one study, 606 pregnancies) and obtain adequate prenatal care defined by number of "procedures" such as testing blood sugar or blood pressure, vaccinations and counseling about breastfeeding and birth control (mean difference (MD) 5.84, 95% CI 1.88 to 9.80, one study, 892 pregnancies). In contrast, women who received incentives were more likely to deliver by cesarean section (RR 1.97, 95% CI 1.18 to 3.30, one study, 979 pregnancies) compared to those women who did not receive incentives.Women who received incentives were no more likely to return for postpartum care based on results of meta-analysis (average RR 0.75, 95% CI 0.21 to 2.64, two studies, 833 pregnancies, Tau² = 0.81, I² = 98%). However, there was substantial heterogeneity in this analysis so a subgroup analysis was performed and this identified a clear difference between subgroups based on the type of incentive being offered. In one study, women receiving non-cash incentives were more likely to return for postpartum care (RR 1.26, 95% CI 1.09 to 1.47, 240 pregnancies) than women who did not receive non-cash incentives. In another study, women receiving cash incentives were less likely to return for postpartum care (RR 0.43, 95% CI 0.30 to 0.62, 593 pregnancies) than women who did not receive cash incentives.No data were identified for the following secondary outcomes: frequency of prenatal care; pre-eclampsia; satisfaction with birth experience; maternal mortality; low birthweight (less than 2500 g); infant macrosomia (birthweight greater than 4000 g); or five-minute Apgar less than seven. AUTHORS' CONCLUSIONS: The included studies did not report on this review's main outcomes: preterm birth, small-for-gestational age, or perinatal death. There is limited evidence that incentives may increase utilization and quality of prenatal care, but may also increase cesarean rate. Overall, there is insufficient evidence to fully evaluate the impact of incentives on prenatal care initiation. There are conflicting data as to the impact of incentives on return for postpartum care. Two of the five studies which accounted for the majority of women in this review were conducted in rural, low-income, overwhelmingly Hispanic communities in Central America, thus limiting the external validity of these results.There is a need for high-quality RCTs to determine whether incentive program increase prenatal care use and improve maternal and neonatal outcomes. Incentive programs, in particular cash-based programs, as suggested in this review and in several observational studies may improve the frequency and ensure adequate quality of prenatal care. No peer-reviewed data have been made publicly available for one of the largest incentive-based prenatal programs - the statewide Medicaid-based programs within the United States. These observational data represent an important starting point for future research with significant implications for policy development and allocation of healthcare resources. The disparate findings related to attending postpartum care should also be further explored as the findings were limited by the number of studies. Future large RCTs are needed to focus on the outcomes of preterm birth, small-for-gestational age and perinatal outcomes

Circumcision bleeding complications: neonatal intensive care infants compared to those in the normal newborn nursery

Purpose: To determine if a significant difference exists in the bleeding complications following circumcision in neonates admitted to neonatal intensive care unit (NICU) versus the normal newborn nursery (NNN). Materials and methods: Observational cohort study of 260 infants undergoing circumcision with Gomco clamp. Vitamin K was given to neonates at delivery. Demographic data, procedural characteristics, bleeding complications, and interventions were recorded. The bleeding rates of the two groups were compared using chi square. Results: NICU neonates experienced increased bleeding complications versus NNN neonates (22% vs. 9.6%, p = .029). No differences were found regarding gestational age at delivery, age at circumcision, and birth weight. Neonates with circumcision performed at ≥5 days of life experienced increased rates of bleeding complications versus those performed at ≤4 days (28% vs. 10.3%, p = .023). All neonates with circumcision performed ≥5 days of life were initially admitted to the NICU. Conclusion: NICU neonates had increased rate of bleeding complications following circumcision when compared to the NNN neonates. There was an increased rate of bleeding complications in neonates who undergo circumcision at ≥5 days of life. Further research may help to determine if redosing of vitamin K or variations in the circumcision procedure are necessary for circumcision at >4 days of life

Increasing Influenza Vaccination Rates in a Busy Urban Clinic

Influenza infection is the cause of thousands of hospitalizations and deaths each year; infection during pregnancy results in increased morbidity and mortality. Underserved women are particularly susceptible to not receiving recommended vaccinations. This project explored the effect of a simple paper based prompt on the influenza vaccination rate in a resident continuity clinic for the underserved. Using this reminder to providers to discuss the influenza vaccination with their patients, we were able to increase vaccination rates in our clinic from 2.2% to 14.2%. This implementation of a simple, low cost, low tech prompt to providers increased the rate of influenza vaccination in our clinic and we present this approach as an easy to implement method of improving vaccination rates. We also suggest this method as an alternative to an alert in the electronic medical record in situations where the electronic medical record may not be accessed during every patient encounter

Translational Systems Pharmacology Studies in Pregnant Women

Pregnancy involves rapid physiological adaptation and complex interplay between mother and fetus. New analytic technologies provide large amounts of genomic, proteomic, and metabolomics data. The integration of these data through bioinformatics, statistical, and systems pharmacology techniques can improve our understanding of the mechanisms of normal maternal physiologic changes and fetal development. New insights into the mechanisms of pregnancy-related disorders, such as preterm birth (PTB), may lead to the development of new therapeutic interventions and novel biomarkers

A new twist to an old story: HE 0450-2958, and the ULIRG→\to (optically bright QSO) transition hypothesis

We report on interferometric imaging of the CO J=1--0 and J=3--2 line emission from the controversial QSO/galaxy pair HE 0450--2958. {\it The detected CO J=1--0 line emission is found associated with the disturbed companion galaxy not the luminous QSO,} and implies $\rm M_{gal}(H_2)\sim (1-2)\times 10^{10} M_{\odot}$, which is \ga 30% of the dynamical mass in its CO-luminous region. Fueled by this large gas reservoir this galaxy is the site of an intense starburst with $\rm SFR\sim 370 M_{\odot} yr^{-1}$, placing it firmly on the upper gas-rich/star-forming end of Ultra Luminous Infrared Galaxies (ULIRGs, $\rm L_{IR}>10^{12} L_{\odot}$). This makes HE 0450--2958 the first case of extreme starburst and powerful QSO activity, intimately linked (triggered by a strong interaction) but not coincident. The lack of CO emission towards the QSO itself renews the controversy regarding its host galaxy by making a gas-rich spiral (the typical host of Narrow Line Seyfert~1 AGNs) less likely. Finally, given that HE 0450--2958 and similar IR-warm QSOs are considered typical ULIRG$\to$(optically bright QSO) transition candidates, our results raise the possibility that some may simply be {\it gas-rich/gas-poor (e.g. spiral/elliptical) galaxy interactions} which ``activate'' an optically bright unobscured QSO in the gas-poor galaxy, and a starburst in the gas-rich one. We argue that such interactions may have gone largely unnoticed even in the local Universe because the combination of tools necessary to disentagle the progenitors (high resolution and S/N optical {\it and} CO imaging) became available only recently.Comment: 25 pages, 5 figures, accepted for publication by The Astrophysical Journa

A retrospective comparison of antibiotic regimens for preterm premature rupture of membranes

OBJECTIVE: To evaluate whether the use of ampicillin and azithromycin leads to a similar latency period in preterm premature rupture of membranes as ampicillin and erythromycin and whether the substitution of azithromycin for erythromycin effects rates of other outcomes. METHODS: We performed a retrospective cohort study of women with preterm premature rupture of membranes between 24 and 34 completed weeks of gestation and compared two groups: those who received ampicillin and erythromycin and those who received ampicillin and azithromycin. Primary outcome was length of latency (defined as time from first antibiotic dose to delivery) and secondary outcomes were rates of chorioamnionitis, cesarean delivery, Apgar scores, birth weight, neonatal death, neonatal sepsis, and neonatal respiratory distress syndrome. RESULTS: Of 168 women who met inclusion criteria, 75 received ampicillin and erythromycin and 93 received ampicillin and azithromycin. There was no difference in latency between groups: 9.6±13.2 days (erythromycin) compared with 9.4±10.0 (azithromycin) days (P=.40). Secondary outcomes did not differ between groups. We had 80% power to detect a difference of 5 days. CONCLUSION: Among women with preterm premature rupture of membranes between 24 and 34 completed weeks of gestation, substitution of azithromycin for erythromycin in the recommended antibiotic regimen did not affect latency or any other measured maternal or fetal outcomes. LEVEL OF EVIDENCE: III

The Characteristics and Potential Ecological Effects of the Exotic Crustacean Zooplankter Cercopagis Pengoi (Cladocera: Ceropagidae), a Recent Invader of Lake Erie

Author Institution: Department of Evolution, Ecology, and Organismal Biology, The Ohio State UniversityThe invasive zooplankter Cercopagis pengoi was recorded for the first time in Lake Erie during August 2001 following previous colonization of Lakes Ontario and Michigan. Cercopagis pengoi (Cladocera: Cercopagidae) is from the Ponto-Caspian region of Eurasia, as is a previous cercopagid invader, Bythotrephes longimanus. Cercopagis tolerates a wide range of salinities and temperatures, has many life history traits characteristic of a successful invader, and has previously invaded the Baltic Sea Cercopagis may affect native zooplankton populations and fish populations through both predation and competition, although the extent of these interactions is not yet known. More research regarding basic life history traits and ecology of Cercopagis is needed to assess the role it will play in Lake Erie