Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 6. Management of pregnancy complications at Community Birthing Centers (Casas Maternas Rurales).

BACKGROUND: In Guatemala, Indigenous women have a maternal mortality ratio over twice that of non-Indigenous women. Long-standing marginalization of Indigenous groups and three decades of civil war have resulted in persistent linguistic, economic, cultural, and physical barriers to maternity care. Curamericas/Guatemala facilitated the development of three community-built, -owned, and -operated birthing centers, Casas Maternas Rurales (referred to here as Community Birthing Centers), where auxiliary nurses provided physically accessible and culturally acceptable clinical care. The objective of this paper is to assess the management of complications and the decision-making pathways of Birthing Center staff for complication management and referral. This is the sixth paper in the series of 10 articles. Birthing centers are part of the Expanded Census-based, Impact-oriented Approach, referred to as CBIO+. METHODS: We undertook an explanatory, mixed-methods study on the handling of pregnancy complications at the Birthing Centers, including a chart review of pregnancy complications encountered among 1,378 women coming to a Birthing Center between 2009 and 2016 and inductively coded interviews with Birthing Center staff. RESULTS: During the study period, 1378 women presented to a Birthing Center for delivery-related care. Of the 211 peripartum complications encountered, 42.2% were successfully resolved at a Birthing Center and 57.8% were referred to higher-level care. Only one maternal death occurred, yielding a maternal mortality ratio of 72.6 maternal deaths per 100,000 live births. The qualitative study found that staff attribute their successful management of complications to frequent, high-quality trainings, task-shifting, a network of consultative support, and a collaborative atmosphere. CONCLUSION: The Birthing Centers were able to resolve almost one-half of the peripartum complications and to promptly refer almost all of the others to a higher level of care, resulting in a maternal mortality ratio less than half that for all Indigenous Guatemalan women. This is the first study we are aware of that analyzes the management of obstetrical complications in such a setting. Barriers to providing high-quality maternity care, including obtaining care for complications, need to be addressed to ensure that all pregnant women in such settings have access to a level of care that is their fundamental human right.

Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ approach of Curamericas: 2. Study site, design, and methods.

BACKGROUND: The Curamericas/Guatemala Maternal and Child Health Project, 2011-2015, included implementation research designed to assess the effectiveness of an approach referred to as CBIO+ , composed of: (1) the Census-Based, Impact-Oriented (CBIO) Approach, (2) the Care Group Approach, and (3) the Community Birthing Center Approach. This is the second paper in a supplement of 10 articles describing the implementation research and its findings. Paper 1 describes CBIO+ , the Project Area, and how the Project was implemented. OBJECTIVE: This paper describes the implementation research design and details of how it was carried out. METHODS: We reviewed the original implementation research protocol and the methods used for all data collection related to this Project. The protocol and methods used for the implementation research related to this Project were all standard approaches to the monitoring and evaluation of child survival projects as developed by the United States Agency for International Development Child Survival and Health Grants Program (CSHGP) and the CORE Group. They underwent independent peer review supervised by the CSHGP before the implementation research began. RESULTS: The study area was divided into two sets of communities with a total population of 98,000 people. Project interventions were implemented in Area A from 2011 until the end of the project in 2015 (44 months) and in Area B from late 2013 until 2015 (20 months). Thus, Area B served as a quasi-comparison area during the first two years of Project implementation. The overarching study question was whether the CBIO+ Approach improved the health and well-being of children and mothers. The outcome indicators included (1) changes in population coverage of evidence-based interventions, (2) changes in childhood nutritional status, (3) changes in the mortality of children and mothers, (4) quality of care provided at Community Birthing Centers, (5) the impact of the Project on women's empowerment and social capital, (6) stakeholder assessment of the effectiveness of the CBIO+ Approach, and (7) the potential of wider adoption of the CBIO+ Approach. CONCLUSION: The implementation research protocol guided the assessment of the effectiveness of the CBIO+ Approach in improving the health and well-being of children, mothers, and their communities.

The birth center model of care: Staffing, business characteristics, and core clinical outcomes.

OBJECTIVES: Interest in expanding access to the birth center model is growing. The purpose of this research is to describe birth center staffing models and business characteristics and explore relationships to perinatal outcomes. METHODS: This descriptive analysis includes a convenience sample of all 84 birth center sites that participated in the AABC Site Survey and AABC Perinatal Data Registry between 2012 and 2020. Selected independent variables include staffing model (CNM/CM or CPM/LM), legal entity status, birth volume/year, and hours of midwifery call/week. Perinatal outcomes include rates of induction of labor, cesarean birth, exclusive breastfeeding, birthweight in pounds, low APGAR scores, and neonatal intensive care admission. RESULTS: The birth center model of care is demonstrated to be safe and effective, across a variety of staffing and business models. Outcomes for both CNM/CM and CPM/LM models of care exceed national benchmarks for perinatal quality with low induction, cesarean, NICU admission, and high rates of breastfeeding. Within the sample of medically low-risk multiparas, variations in clinical outcomes were correlated with business characteristics of the birth center, specifically annual birth volume. Increased induction of labor and cesarean birth, with decreased success breastfeeding, were present within practices characterized as high volume (>200 births/year). The research demonstrates decreased access to the birth center model of care for Black and Hispanic populations. CONCLUSIONS FOR PRACTICE: Between 2012 and 2020, 84 birth centers across the United States engaged in 90,580 episodes of perinatal care. Continued policy development is necessary to provide risk-appropriate care for populations of healthy, medically low-risk consumers.

Does interpregnancy BMI change affect the risk of complications in the second pregnancy? Analysis of pooled data from Aberdeen, Finland and Malta.

OBJECTIVE: Weight management interventions during pregnancy have had limited success in reducing the risk of pregnancy complications. Focus has now shifted to pre-pregnancy counselling to optimise body weight before subsequent conception. We aimed to assess the effect of interpregnancy body mass index (BMI) change on the risk of perinatal complications in the second pregnancy. METHODS: A cohort study was performed using pooled maternity data from Aberdeen, Finland and Malta. Women with a BMI change of ±2 kg/m2 between their first and second pregnancies were compared with those who were BMI stable (remained within ±2 kg/m2). Outcomes assessed included pre-eclampsia (PE), intrauterine growth restriction (IUGR), preterm birth, birth weight, and stillbirth in the second pregnancy. We also assessed the effect of unit change in BMI for PE and IUGR. Logistic regression was used to calculate odds ratios with 95% confidence intervals. RESULTS: An increase of ≥2 kg/m2 between the first two pregnancies increased the risk of PE (1.66 (1.49-1.86)) and high birthweight (>4000 g) (1.06 (1.03-1.10)). A reduction of ≥2 kg/m2 increased the chance of IUGR (1.15 (1.01-1.31)) and preterm birth (1.14 (1.01-1.30)), while reducing the risk of instrumental delivery (0.75 (0.68-0.85)) and high birthweight (0.93 (0.87-0.98)). Reducing BMI did not significantly decrease PE risk in women with obesity or those with previous PE. A history of PE or IUGR in the first pregnancy was the strongest predictor of recurrence independent of interpregnancy BMI change (5.75 (5.30-6.24) and (7.44 (6.71-8.25), respectively). CONCLUSION: Changes in interpregnancy BMI have a modest impact on the risk of high birthweight, PE and IUGR in contrasting directions. However, a prior history of PE and IUGR is the dominant predictor of recurrence at second pregnancy.

The importance of nutrition in pregnancy and lactation: lifelong consequences.

Most women in the United States do not meet the recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman should look like. The message should be "eat better, not more." This can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report "prudent" or "health-conscious" eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants.

Early pregnancy weight gain and fat accrual predict pregnancy outcome in growing adolescent sheep.

The competition for nutrients when pregnancy coincides with continuing growth in biologically immature adolescent girls increases their risk of preterm delivery and low birthweight and is partly replicated in the overnourished adolescent sheep paradigm. Although overfeeding to promote rapid maternal growth robustly leads to a reduction in average birthweight relative to slow-growing control-fed adolescents of equivalent age, the extent of prenatal compromise is variable. This retrospective analysis of a large cohort of identically managed pregnancies determined whether maternal anthropometry predicts the severity of fetal growth-restriction (FGR) in growing adolescents. Singleton pregnancies were established by embryo transfer in adolescents subsequently control-fed (n = 96) or overnourished. The latter pregnancies were classified as non-FGR (n = 116) or FGR (n = 96) if lamb birthweight was above or below the optimally fed control mean minus 2SD. A similar approach categorised placental growth-restriction (PlGR) and preterm delivery. Gestation length, placental mass and lamb birthweight were FGR < non-FGR < control (post hoc P < 0.01). Relative to the non-FGR group, overnourished dams with FGR were marginally leaner and lighter at conception (P = 0.023/P = 0.014) and had greater gestational weight gain (GWG) during the first-third of pregnancy (P < 0.001). GWG during this early period was also higher in PlGR compared with non-PlGR, and in very preterm vs term deliveries (P < 0.01). Likewise maternal leptin concentrations (fat accrual biomarker) were FGR > non-FGR by day 60, and changes in leptin throughout pregnancy predicted attenuated fetal cotyledon mass and birthweight (P = 0.01 to <0.001). The anthropometric antecedents of FGR in still-growing adolescent sheep originate in early pregnancy coincident with early placental development.

Dysregulated actin dynamics in activated PI3Kδ syndrome.

Activated PI3Kδ syndrome (APDS) Type I results from gain-of-function mutations in PIK3CD, which encodes the p110δ subunit of PI3Kδ. Abnormal actin dynamics have been hypothesized to contribute to the lymphopenia associated with this disease but have not been studied in patients with APDS. We report a patient with APDS who had widespread necrotic skin lesions that were responsive specifically to immunosuppressive therapy. EBV-transformed lymphoblastoid cells (EBV-LCLs) from patients with APDS exhibit increased polymerized actin and increased apoptosis, suggesting a contribution of impaired actin dynamics to this disease.

Immunodeficiency and EBV-induced lymphoproliferation caused by 4-1BB deficiency.

BACKGROUND: The tumor TNF receptor family member 4-1BB (CD137) is encoded by TNFRSF9 and expressed on activated T cells. 4-1BB provides a costimulatory signal that enhances CD8+ T-cell survival, cytotoxicity, and mitochondrial activity, thereby promoting immunity against viruses and tumors. The ligand for 4-1BB is expressed on antigen-presenting cells and EBV-transformed B cells. OBJECTIVE: We investigated the genetic basis of recurrent sinopulmonary infections, persistent EBV viremia, and EBV-induced lymphoproliferation in 2 unrelated patients. METHODS: Whole-exome sequencing, immunoblotting, immunophenotyping, and in vitro assays of lymphocyte and mitochondrial function were performed. RESULTS: The 2 patients shared a homozygous G109S missense mutation in 4-1BB that abolished protein expression and ligand binding. The patients' CD8+ T cells had reduced proliferation, impaired expression of IFN-γ and perforin, and diminished cytotoxicity against allogeneic and HLA-matched EBV-B cells. Mitochondrial biogenesis, membrane potential, and function were significantly reduced in the patients' activated T cells. An inhibitory antibody against 4-1BB recapitulated the patients' defective CD8+ T-cell activation and cytotoxicity against EBV-infected B cells in vitro. CONCLUSION: This novel immunodeficiency demonstrates the critical role of 4-1BB costimulation in host immunity against EBV infection.

A novel truncating mutation in MYD88 in a patient with BCG adenitis, neutropenia and delayed umbilical cord separation.

Mutations in MYD88 cause susceptibility to invasive bacterial infections through impaired signaling downstream of toll-like receptors (TLRs) and IL-1 receptors. We studied a patient presenting with neutropenia, delayed umbilical cord separation, BCG adenitis, andP. aeruginosapneumonia. Next-generation DNA sequencing identified a novel homozygous truncation mutation in MYD88 that abolishes MyD88 expression. The patient's dermal fibroblasts had severely impaired IL-6 production after stimulation with ligands for the MyD88-dependent receptors TLR2, TLR4 and IL-1R, while responses to ligands for the MyD88-independent receptors TLR3 and TNF-α were preserved. Notably, secretion of TNF-α, which is essential for BCG control, was also impaired after LPS stimulation. In this first report of BCG infection in MyD88 deficiency, data suggest that MyD88-dependent TNF-α production contributes to control of mycobacterial disease.

Using a Birth Center Model of Care to Improve Reproductive Outcomes in Informal Settlements-a Case Study.

The world is becoming increasingly urban. For the first time in history, more than 50% of human beings live in cities (United Nations, Department of Economic and Social Affairs, Population Division, ed. (2015)). Rapid urbanization is often chaotic and unstructured, leading to the formation of informal settlements or slums. Informal settlements are frequently located in environmentally hazardous areas and typically lack adequate sanitation and clean water, leading to poor health outcomes for residents. In these difficult circumstances women and children fair the worst, and reproductive outcomes for women living in informal settlements are grim. Insufficient uptake of antenatal care, lack of skilled birth attendants and poor-quality care contribute to maternal mortality rates in informal settlements that far outpace wealthier urban neighborhoods (Chant and McIlwaine (2016)). In response, a birth center model of maternity care is proposed for informal settlements. Birth centers have been shown to provide high quality, respectful, culturally appropriate care in high resource settings (Stapleton et al. J Midwifery Women's Health 58(1):3-14, 2013; Hodnett et al. Cochrane Database Syst Rev CD000012, 2012; Brocklehurst et al. BMJ 343:d7400, 2011). In this paper, three case studies are described that support the use of this model in low resource, urban settings.

Ovine prenatal growth restriction impacts glucose metabolism and body composition throughout life in both sexes.

Low birthweight is a risk factor for later adverse health. Here the impact of placentally mediated prenatal growth restriction followed by postnatal nutrient abundance on growth, glucose metabolism and body composition was assessed in both sexes at key stages from birth to mid-adult life. Singleton-bearing adolescent dams were fed control or high nutrient intakes to induce normal or growth-restricted pregnancies respectively. Restricted lambs had ~40% reduced birthweight. Fractional growth rates were higher in restricted lambs of both sexes predominantly during suckling/juvenile phases. Thereafter, rates and patterns of growth differed by sex. Absolute catch-up was not achieved and restricted offspring had modestly reduced weight and stature at mid-adulthood necropsy (~109 weeks). Dual-energy X-ray absorptiometry revealed lower bone mineral density in restricted vs normal lambs at 11, 41, 64 and 107 weeks, with males > females from 41 weeks onwards. Body fat percentage was higher in females vs males throughout, in restricted vs normal lambs at weaning (both sexes) and in restricted vs normal females at mid-adulthood. Insulin secretion after glucose challenge was greater in restricted vs normal of both sexes at 7 weeks and in restricted males at 32 weeks. In both sexes, fasting glucose concentrations were greater in restricted offspring across the life course, while glucose area under the curve after challenge was higher in restricted offspring at 32, 60, 85 and 106 weeks, indicative of persistent glucose intolerance. Therefore, prenatal growth restriction has negative consequences for body composition and metabolism throughout the life course with the effects modulated by sex differences in postnatal growth rates, fat deposition and bone mass accrual.

Impact of donor and recipient adiposity on placental and fetal growth in adolescent sheep.

The influence of maternal obesity during oocyte development and its putative interaction with nutrient reserves at conception on pregnancy outcome were examined in an adolescent sheep model. Donor ewes were nutritionally managed to achieve contrasting adiposity (control (CD)/obese (ObD)) for 6 weeks prior to superovulation and inseminated by a non-obese sire. Morulae from 6 CD and 7 ObD were transferred in singleton into adolescent recipients of identical age but differing adiposity, classified as relatively fat or thin respectively. Thereafter, all were overnourished to promote rapid growth/adiposity (2 × 2 design, 13/14 pregnancies/group). A fifth recipient group of intermediate adiposity received embryos from another 5 CD, was offered a moderate intake to maintain adiposity throughout gestation and acted as controls for normal pregnancy outcome (optimally treated control (OTC), 19 pregnancies). Donor obesity did not influence ovulation, fertilisation or recovery rates or impact embryo morphology. Gestation length and colostrum yield were unaffected by donor or recipient adiposity and were reduced relative to OTC. Total fetal cotyledon and lamb birth weights were independent of initial donor adiposity but reduced in relatively thin vs relatively fat recipients and lower than those in the OTC group. In spite of high placental efficiency, the incidence of fetal growth restriction was greatest in the thin recipients. Thus, maternal adiposity at conception, but not pre-conception maternal obesity, modestly influences the feto-placental growth trajectory, whereas comparison with the OTC indicates that high gestational intakes to promote rapid maternal growth remain the dominant negative influence on pregnancy outcome in young adolescents. These findings inform dietary advice for pregnant adolescent girls.

Peri- and Postnatal Effects of Prenatal Adenoviral VEGF Gene Therapy in Growth-Restricted Sheep.

Uterine artery (UtA) adenovirus (Ad) vector-mediated overexpression of vascular endothelial growth factor (VEGF) enhances uterine blood flow in normal sheep pregnancy and increases fetal growth in the overnourished adolescent sheep model of fetal growth restriction (FGR). Herein, we examined its impact on gestation length, neonatal survival, early postnatal growth and metabolism. Singleton-bearing ewes were evenly allocated to receive Ad.VEGF-A165 (5 × 10(10) particles/ml, 10 ml, n = 17) or saline (10 ml, n = 16) injected into each UtA at laparotomy (0.6 gestation). Fetal growth was serially monitored (blind) by ultrasound until delivery. Lambs were weighed and blood was sampled weekly and a glucose tolerance test performed (68-day postnatal age). Hepatic DNA/RNA was extracted at necropsy (83-day postnatal age) to examine methylation status of eight somatotropic axis genes. IGF1 mRNA and protein expression were measured by RT-PCR and radioimmunoassay, respectively. All pregnancies remained viable following Ad.VEGF-A165 treatment. Fetal abdominal circumference and renal volume were greater in the Ad.VEGF-A165 group compared with the saline group at 21/28 days (P ≤ 0.04) postinjection. At delivery, gestation length (P = 0.07), lamb birthweight (P = 0.08), umbilical girth (P = 0.06), and plasma glucose (P = 0.09) tended to be greater in Ad.VEGF-A165-treated lambs. Levels of neonatal intervention required to ensure survival was equivalent between groups. Absolute postnatal growth rate (P = 0.02), insulin area under the curve (P = 0.04) and carcass weight at necropsy (P = 0.04) were increased by Ad.VEGF-A165 treatment. There was no impact on markers of insulin sensitivity or methylation/expression of key genes involved in somatic growth. Ad.VEGF-A165 gene therapy increased fetal growth in a sheep FGR model, and lambs continued to thrive during the neonatal and early postnatal period.