by Ank de Jonge, Jane SandallIn a Perspective, Ank de Jonge and Jane Sandall discuss research on models of maternity care led by midwives.
A Comparison of Midwife-Led and Medical-Led Models of Care and Their Relationship to Adverse Fetal and Neonatal Outcomes: A Retrospective Cohort Study in New Zealand
by Ellie Wernham, Jason Gurney, James Stanley, Lis Ellison-Loschmann, Diana SarfatiBackground
Internationally, a typical model of maternity care is a medically led system with varying levels of midwifery input. New Zealand has a midwife-led model of care, and there are movements in other countries to adopt such a system. There is a paucity of systemic evaluation that formally investigates safety-related outcomes in relationship to midwife-led care within an entire maternity service. The main objective of this study was to compare major adverse perinatal outcomes between midwife-led and medical-led maternity care in New Zealand.Methods and Findings
This was a population-based retrospective cohort study. Participants were mother/baby pairs for all 244,047 singleton, term deliveries occurring between 1 January 2008 and 31 December 2012 in New Zealand in which no major fetal, neonatal, chromosomal or metabolic abnormality was identified and the mother was first registered with a midwife, obstetrician, or general practitioner as lead maternity carer. Main outcome measures were low Apgar score at five min, intrauterine hypoxia, birth-related asphyxia, neonatal encephalopathy, small for gestational age (as a negative control), and mortality outcomes (perinatal related mortality, stillbirth, and neonatal mortality). Logistic regression models were fitted, with crude and adjusted odds ratios (ORs) generated for each outcome for midwife-led versus medical-led care (based on lead maternity carer at first registration) with 95% confidence intervals. Fully adjusted models included age, ethnicity, deprivation, trimester of registration, parity, smoking, body mass index (BMI), and pre-existing diabetes and/or hypertension in the model. Of the 244,047 pregnancies included in the study, 223,385 (91.5%) were first registered with a midwife lead maternity carer, and 20,662 (8.5%) with a medical lead maternity carer. Adjusted ORs showed that medical-led births were associated with lower odds of an Apgar score of less than seven at 5 min (OR 0.52; 95% confidence interval 0.43–0.64), intrauterine hypoxia (OR 0.79; 0.62–1.02), birth-related asphyxia (OR 0.45; 0.32–0.62), and neonatal encephalopathy (OR 0.61; 0.38–0.97). No association was found between lead carer at first registration and being small for gestational age (SGA), which was included as a negative control (OR 1.00; 0.95–1.05). It was not possible to definitively determine whether one model of care was associated with fewer infant deaths, with ORs for the medical-led model compared with the midwife-led model being 0.80 (0.54–1.19) for perinatal related mortality, 0.86 (0.55–1.34) for stillbirth, and 0.62 (0.25–1.53) for neonatal mortality. Major limitations were related to the use of routine data in which some variables lacked detail; for example, we were unable to differentiate the midwife-led group into those who had received medical input during pregnancy and those who had not.Conclusions
There is an unexplained excess of adverse events in midwife-led deliveries in New Zealand where midwives practice autonomously. The findings are of concern and demonstrate a need for further research that specifically investigates the reasons for the apparent excess of adverse outcomes in mothers with midwife-led care. These findings should be interpreted in the context of New Zealand’s internationally comparable birth outcomes and in the context of research that supports the many benefits of midwife-led care, such as greater patient satisfaction and lower intervention rates.
Tenofovir Pre-exposure Prophylaxis for Pregnant and Breastfeeding Women at Risk of HIV Infection: The Time is Now
by Lynne M. MofensonIn this Perspective, Lynne Mofenson discusses the implications of Mugwanya and colleagues' findings for protection of women against HIV infection during breastfeeding.
Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption
by Kenneth K. Mugwanya, Craig W. Hendrix, Nelly R. Mugo, Mark Marzinke, Elly T. Katabira, Kenneth Ngure, Nulu B. Semiyaga, Grace John-Stewart, Timothy R. Muwonge, Gabriel Muthuri, Andy Stergachis, Connie L. Celum, Jared M. BaetenBackground
As pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women.Methods and Findings
We conducted a prospective short-term, open-label study of daily oral emtricitabine–tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother–infant pairs between 1–24 wk postpartum (ClinicalTrials.gov Identifier: NCT02776748). The primary goal was to quantify the steady-state concentrations of tenofovir and emtricitabine in infant plasma ingested via breastfeeding. PrEP was administered to women through daily directly observed therapy (DOT) for ten consecutive days and then discontinued thereafter. Non-fasting peak and trough samples of maternal plasma and breast milk were obtained at drug concentration steady states on days 7 and 10, and a single infant plasma sample was obtained on day 7. Peak blood and breast milk samples were obtained 1–2 h after the maternal DOT PrEP dose, while maternal trough samples were obtained at the end of the PrEP dosing interval (i.e., 23 to 24 h) after maternal DOT PrEP dose. Tenofovir and emtricitabine concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays.Of the 50 mother–infant pairs enrolled, 48% were ≤12 wk and 52% were 13–24 wk postpartum, and median maternal age was 25 y (interquartile range [IQR] 22–28). During study follow-up, the median (IQR) daily reported frequency of infant breastfeeding was 15 times (12 to 18) overall, 16 (14 to 19) for the ≤12 weeks, and 14 (12 to 17) for the 13–24 wk infant age groups. Overall, median (IQR) time-averaged peak concentrations in breast milk were 3.2 ng/mL (2.3 to 4.7) for tenofovir and 212.5 ng/mL (140.0 to 405.0) for emtricitabine. Similarly, median (IQR) time-averaged trough concentrations in breast milk were 3.3 ng/mL (2.3 to 4.4) for tenofovir and 183.0 ng/mL (113.0 to 250.0) for emtricitabine, reflecting trough-to-peak breast milk concentration ratios of 1.0 for tenofovir and 0.8 for emtricitabine, respectively. In infant plasma, tenofovir was unquantifiable in 46/49 samples (94%), but emtricitabine was detectable in 47/49 (96%) (median [IQR] concentration: 13.2 ng/mL [9.3 to 16.7]). The estimated equivalent doses an infant would ingest daily from breastfeeding were 0.47 μg/kg (IQR 0.35 to 0.71) for tenofovir and 31.9 μg/kg (IQR 21.0 to 60.8) for emtricitabine, translating into a <0.01% and 0.5% relative dose when compared to the 6 mg/kg dose that is proposed for therapeutic treatment of infant HIV infection and for prevention of infant postnatal HIV infection; a dose that has not shown safety concerns. No serious adverse effects were recorded during study follow-up.The key study limitation was that only a single infant sample was collected to minimize venipunctures for the children. However, maternal daily DOT and specimen collection at drug concentration steady state provided an adequate approach to address the key research question. Importantly, there was minimal variation in breast milk concentrations of tenofovir and emtricitabine (respective median trough-to-peak concentration ratio ~1), demonstrating that infants were exposed to consistent drug dosing via breast milk.Conclusion
In this short-term study of daily directly observed oral PrEP in HIV-uninfected breastfeeding women, the estimated infant doses from breast milk and resultant infant plasma concentrations for tenofovir and emtricitabine were 12,500 and >200-fold lower than the respective proposed infant therapeutic doses, and tenofovir was not detected in 94% of infant plasma samples. These data suggest that PrEP can be safely used during breastfeeding with minimal infant drug exposure.Trial Registration
ClinicalTrials.gov, Identifier: NCT02776748
A Public Health Framework for Legalized Retail Marijuana Based on the US Experience: Avoiding a New Tobacco Industry
by Rachel Ann Barry, Stanton GlantzRachel Barry and Stanton Glantz argue that a public health framework that prioritizes public health over business interests should be used by US states and countries that legalize retail marijuana.