Impact of the Salud Mesoamerica Initiative on delivery care choices in Guatemala, Honduras, and Nicaragua.

BACKGROUND: The Salud Mesoamérica Initiative (SMI) is a public-private collaboration aimed to improve maternal and child health conditions in the poorest populations of Mesoamerica through a results-based aid mechanism. We assess the impact of SMI on the staffing and availability of equipment and supplies for delivery care, the proportion of institutional deliveries, and the proportion of women who choose a facility other than the one closest to their locality of residence for delivery. METHODS: We used a quasi-experimental design, including baseline and follow-up measurements between 2013 and 2018 in intervention and comparison areas of Guatemala, Nicaragua, and Honduras. We collected information on 8754 births linked to the health facility closest to the mother's locality of residence and the facility where the delivery took place (if attended in a health facility). We fit difference-in-difference models, adjusting for women's characteristics (age, parity, education), household characteristics, exposure to health promotion interventions, health facility level, and country. RESULTS: Equipment, inputs, and staffing of facilities improved after the Initiative in both intervention and comparison areas. After adjustment for covariates, institutional delivery increased between baseline and follow-up by 3.1 percentage points (ß = 0.031, 95% CI -0.03, 0.09) more in intervention areas than in comparison areas. The proportion of women in intervention areas who chose a facility other than their closest one to attend the delivery decreased between baseline and follow-up by 13 percentage points (ß = - 0.130, 95% CI -0.23, - 0.03) more than in the comparison group. CONCLUSIONS: Results indicate that women in intervention areas of SMI are more likely to go to their closest facility to attend delivery after the Initiative has improved facilities' capacity, suggesting that results-based aid initiatives targeting poor populations, like SMI, can increase the use of facilities closest to the place of residence for delivery care services. This should be considered in the design of interventions after the COVID-19 pandemic may have changed health and social conditions.

Fetal growth patterns in pregnancy-associated hypertensive disorders: NICHD Fetal Growth Studies.

BACKGROUND: Fetal growth patterns in pregnancy-associated hypertensive disorders is poorly understood because prospective longitudinal data are lacking. OBJECTIVE: The objective of the study was to compare longitudinal fetal growth trajectories between normotensive women and those with pregnancy-associated hypertensive disorders. STUDY DESIGN: This is a study based on data from a prospective longitudinal cohort study of fetal growth performed at 12 US sites (2009-2013). Project gestational age was confirmed by ultrasound between 8 weeks 0 days and 13 weels 6 days, and up to 6 ultrasounds were performed across gestation. Hypertensive disorders were diagnosed based on 2002 American College of Obstetricians and Gynecologists guidelines and grouped hierarchically as severe preeclampsia (including eclampsia or HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome), mild preeclampsia, severe gestational hypertension, mild gestational hypertension, or unspecified hypertension. Women without any hypertensive disorder constituted the normotensive group. Growth curves for estimated fetal weight and individual biometric parameters including biparietal diameter, head circumference, abdominal circumference, and femur and humerus length were calculated for each group using linear mixed models with cubic splines. Global and weekly pairwise comparisons were performed between women with a hypertensive disorder compared with normotensive women to analyze differences while adjusting for confounding variables. Delivery gestational age and birthweights were compared among groups. RESULTS: Of 2462 women analyzed, 2296 (93.3%) were normotensive, 63 (2.6%) had mild gestational hypertension, 54 (2.2%) mild preeclampsia, 32 (1.3%) severe preeclampsia, and 17 (0.7%) unspecified hypertension. Compared with normotensive women, those with severe preeclampsia had estimated fetal weights that were reduced between 22 and 38 weeks (all weekly pairwise values of P < .008). Women with severe preeclampsia compared with those without hypertension also had significantly smaller fetal abdominal circumference between 23-31 and 33-37 weeks' gestation (weekly pairwise values of P < .04). Scattered weekly growth differences were noted on other biometric parameters between these 2 groups. The consistent differences in estimated fetal weight and abdominal circumference were not observed between women with other hypertensive disorders and those who were normotensive. Women with severe preeclampsia delivered significantly earlier (mean gestational age 35.9 ± 3.2 weeks) than the other groups (global P < .0001). Birthweights in the severe preeclampsia group were also significantly lower (mean -949.5 g [95% confidence interval, -1117.7 to -781.2 g]; P < .0001) than in the normotensive group. CONCLUSION: Among women with pregnancy-associated hypertensive disorders, only those destined to develop severe preeclampsia demonstrated a significant and consistent difference in fetal growth (ie, smaller estimated fetal weight and abdominal circumference) when compared with normotensive women.

Salud Mesoamérica 2015 Initiative: design, implementation, and baseline findings.

BACKGROUND: Health has improved markedly in Mesoamerica, the region consisting of southern Mexico and Central America, over the past decade. Despite this progress, there remain substantial inequalities in health outcomes, access, and quality of medical care between and within countries. Poor, indigenous, and rural populations have considerably worse health indicators than national or regional averages. In an effort to address these health inequalities, the Salud Mesoamérica 2015 Initiative (SM2015), a results-based financing initiative, was established. METHODS: For each of the eight participating countries, health targets were set to measure the progress of improvements in maternal and child health produced by the Initiative. To establish a baseline, we conducted censuses of 90,000 households, completed 20,225 household interviews, and surveyed 479 health facilities in the poorest areas of Mesoamerica. Pairing health facility and household surveys allows us to link barriers to care and health outcomes with health system infrastructure components and quality of health services. RESULTS: Indicators varied significantly within and between countries. Anemia was most prevalent in Panama and least prevalent in Honduras. Anemia varied by age, with the highest levels observed among children aged 0 to 11 months in all settings. Belize had the highest proportion of institutional deliveries (99%), while Guatemala had the lowest (24%). The proportion of women with four antenatal care visits with a skilled attendant was highest in El Salvador (90%) and the lowest in Guatemala (20%). Availability of contraceptives also varied. The availability of condoms ranged from 83% in Nicaragua to 97% in Honduras. Oral contraceptive pills and injectable contraceptives were available in just 75% of facilities in Panama. IUDs were observed in only 21.5% of facilities surveyed in El Salvador. CONCLUSIONS: These data provide a baseline of much-needed information for evidence-based action on health throughout Mesoamerica. Our baseline estimates reflect large disparities in health indicators within and between countries and will facilitate the evaluation of interventions and investments deployed in the region over the next three to five years. SM2015's innovative monitoring and evaluation framework will allow health officials with limited resources to identify and target areas of greatest need.

Relationship between maternal and newborn endothelial function and oxidative stress.

OBJECTIVE: To evaluate the Relationship between maternal and newborn endothelial function and oxidative stress. METHODS: Forty-three pregnant women and their offspring were evaluated. As markers of endothelial function, the flow-mediated dilation (FMD) was measured in pregnant women in the second and third trimesters, and nitric oxide (NO) was quantified in the endothelial cells of the umbilical cord vein. Malondialdehyde (MDA), as a marker of oxidative stress, was measured in the maternal plasma (second and third trimesters) and plasma from umbilical cord blood. Gestational age and birth weight were recorded. Correlations between variables were estimated, and adjustments were made for specific gestational week of measurement, gestational age at birth, and complications during pregnancy and/or at delivery. RESULTS: Maternal FMD at second trimester correlated positively with newborn MDA, although with marginal significance (P = 0.090). The change in maternal FMD was positively correlated with newborn NO (P = 0.039), although adjustment for gestational age and specific week of gestation attenuated this relationship (P = 0.070). Maternal MDA at second trimester correlated positively with newborn MDA independently of gestational age at birth, specific week of gestation of the measurement, and having complications during pregnancy or at delivery (P = 0.032). After adjustments, the change in maternal MDA correlated with newborn MDA but marginally (P = 0.077). CONCLUSION: Study findings suggest that under physiological conditions, enhanced endothelial function and/or oxidative stress in the mother may impact on normal fetal development. Future studies are recommended, employing larger sample sizes, a more extensive set of markers of oxidative stress, and comparisons of complicated versus normal pregnancies.

Hypertensive Disorders of Pregnancy and Pre-Pregnancy Hypertension with Subsequent Incident Venous Thromboembolic Events.

Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension contribute to maternal morbidity and mortality. We examined the association of HDP and pre-pregnancy hypertension with subsequent venous thromboembolic (VTE) events. The retrospective cohort study included 444,859 women with ≥1 live, singleton birth in South Carolina (2004-2016). Hospital and emergency department visit and death certificate data defined incident VTE, HDP, and pre-pregnancy hypertension. Birth certificate data also defined the exposures. Adjusted Cox proportional hazards methods modeled VTE events risk. Of the cohort, 2.6% of women had pre-pregnancy hypertension, 5.8% had HDP, 2.8% had both pre-pregnancy hypertension and HDP (both conditions), and 88.8% had neither condition. The risk of incident VTE events within one year of delivery was higher in women with HDP (hazard ratio [HR] = 1.62, 95% confidence interval [CI]: 1.15-2.29) and both conditions (HR = 2.32, 95% CI: 1.60-3.35) compared to those with neither condition as was the risk within five years for women with HDP (HR = 1.35, 95% CI: 1.13-1.60) and for women with both conditions (HR = 1.82, 95% CI: 1.50-2.20). One- and five-year risks did not differ in women with pre-pregnancy hypertension compared to women with neither condition. Compared to non-Hispanic White (NHW) women with neither condition, the incident VTE event risk was elevated within five years of delivery for NHW (HR = 1.29, 95% CI: 1.02-1.63; HR = 1.59, 95% CI: 1.16-2.17) and non-Hispanic Black (NHB; HR = 1.51, 95% CI: 1.16-2.96; HR = 2.08, 95% CI: 1.62-2.66) women with HDP and with both conditions, respectively, and for NHB women with pre-pregnancy hypertension (HR = 1.50, 95% CI: 1.09-2.07). VTE event risk was highest in women with HDP, and the event rates were higher in NHB women than in NHW women in the same exposure group.

The Association of Hypertensive Disorders of Pregnancy with Infant Mortality, Preterm Delivery, and Small for Gestational Age.

Gestational hypertension, preeclampsia, eclampsia, and chronic hypertension (CHTN) are associated with adverse infant outcomes and disproportionately affect minoritized race/ethnicity groups. We evaluated the relationships between hypertensive disorders of pregnancy (HDP) and/or CHTN with infant mortality, preterm delivery (PTD), and small for gestational age (SGA) in a statewide cohort with a diverse racial/ethnic population. All live, singleton deliveries in South Carolina (2004-2016) to mothers aged 12-49 were evaluated for adverse outcomes: infant mortality, PTD (20 to less than <37 weeks) and SGA (<10th birthweight-for-gestational-age percentile). Logistic regression models adjusted for sociodemographic, behavioral, and clinical characteristics. In 666,905 deliveries, mothers had superimposed preeclampsia (HDP + CHTN; 1.0%), HDP alone (8.0%), CHTN alone (1.8%), or no hypertension (89.1%). Infant mortality risk was significantly higher in deliveries to women with superimposed preeclampsia, HDP, and CHTN compared with no hypertension (relative risk [RR] = 1.79, 1.39, and 1.48, respectively). After accounting for differing risk by race/ethnicity, deliveries to women with HDP and/or CHTN were more likely to result in PTD (RRs ranged from 3.14 to 5.25) or SGA (RRs ranged from 1.67 to 3.64). As CHTN, HDP and superimposed preeclampsia confer higher risk of adverse outcomes, prevention efforts should involve encouraging and supporting mothers in mitigating modifiable cardiovascular risk factors.

Dataset of media practices for informational, educational, and entertainment purposes in Peru: Uses and gratifications approach.

This database consists of the Peruvian media diet in a post-pandemic context. Specifically, it examines how Peruvians define and utilise media to create environments for information, learning, and entertainment. Since the pandemic, the relationship that users have developed with the media has intensified and changed, fostering new uses and interactions. However, our data demonstrates that the Peruvian public maintains a critical role towards mass media (broadcasting model) [1], which motivates them to seek out media and platforms that cater to their interests and expectations. In this regard, we compare three axes of analysis (information, education, and entertainment), taking socio demographic variables, to produce a baseline that is useful for specific research projects. Through a quantitative approach we explored the expectations, decisions, forms of interaction, and satisfactions that users obtain in their relationship with the media, offering new theoretical insights based on emerging data, such as the level of planning in content consumption or the role that traditional media play in different age and socioeconomic groups.

Concurrent progestogen and cerclage to reduce preterm birth: a multicenter international retrospective cohort.

BACKGROUND: Both progestogens and cerclage are individually effective in preterm birth prevention in high risk pregnancies. However, national and international guidelines cite a lack of data available to comment on the potential benefit of concurrent progestogen therapy after cerclage has been placed. Studies to date have been small with mixed results regarding benefit of concurrent progestogen with cerclage leaving uncertainty regarding best clinical practice. OBJECTIVE: This study aimed to evaluate whether cerclage with progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth in singleton pregnancies. METHODS: This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016 to June 2020. Exclusion criteria were lack of documentation regarding whether progestogen was prescribed, unavailable delivery outcome, and pregnancy termination (spontaneous or induced) before 16 weeks' gestation. The exposure of interest was progestogen use with cerclage placement, which included those who continued to use progestogen or who started progestogen after cerclage. The comparison group consisted of those without progestogen use after cerclage placement, which included those who had no progestogen use during the entire pregnancy or who initiated progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. The primary outcome was spontaneous preterm birth at <37 weeks. The secondary outcomes were spontaneous preterm birth at <34 weeks, gestational age at delivery, and a composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, and bronchopulmonary dysplasia. There were planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate), preterm birth history, and site. Continuous variables were compared in adjusted analyses with analysis of covariance, and categorical variables were compared with multivariable logistic regression, adjusting for potential confounders with adjusted odds ratio. A Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks. RESULTS: During the study period, a total of 699 singletons met the inclusion criteria: 561 in the progestogen with cerclage group and 138 with cerclage alone. Baseline characteristics were similar, except the higher likelihood of previous spontaneous preterm birth in the progestogen group (61% vs 41%; P<.001). Within the progestogen group, 52% were on 17-hydroxyprogesterone caproate weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of spontaneous preterm birth <37 weeks (31% vs 39%; adjusted odds ratio, 0.59 [0.39-0.89]; P=.01) and <34 weeks (19% vs 27%; adjusted odds ratio, 0.55 [0.35-0.87]; P=.01), increased latency to spontaneous delivery (hazard ratio for spontaneous preterm birth <37 weeks, 0.66 [0.49-0.90]; P=.009), and lower frequency of perinatal death (7% vs 16%; adjusted odds ratio, 0.37 [0.20-0.67]; P=.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a previous preterm birth, those with ultrasound- or examination-indicated cerclage, those who started progestogen therapy before cerclage, and in sites restricted to the United States. CONCLUSION: Use of progestogen with cerclage was associated with reduced rates of spontaneous preterm birth and early spontaneous preterm birth compared with cerclage alone. Although this study was not sufficiently powered for subgroup analysis, the strength of evidence for benefit appeared greatest for those with ultrasound- or examination-indicated cerclage, and with vaginal progesterone. El resumen está disponible en Español al final del artículo.

Increasing Preterm Delivery and Small for Gestational Age Trends in South Carolina during the COVID-19 Pandemic.

Preterm delivery (PTD) complications are a major cause of childhood morbidity and mortality. We aimed to assess trends in PTD and small for gestational age (SGA) and whether trends varied between race-ethnic groups in South Carolina (SC). We utilized 2015-2021 SC vital records linked to hospitalization and emergency department records. PTD was defined as clinically estimated gestation less than (<) 37 weeks (wks.) with subgroup analyses of PTD < 34 wks. and < 28 wks. SGA was defined as infants weighing below the 10th percentile for gestational age. This retrospective study included 338,532 (243,010 before the COVID-19 pandemic and 95,522 during the pandemic) live singleton births of gestational age ≥ 20 wks. born to 260,276 mothers in SC. Generalized estimating equations and a change-point during the first quarter of 2020 helped to assess trends. In unadjusted analyses, pre-pandemic PTD showed an increasing trend that continued during the pandemic (relative risk (RR) = 1.04, 95% CI: 1.02-1.06). PTD < 34 wks. rose during the pandemic (RR = 1.07, 95% CI: 1.02-1.12) with a significant change in the slope. Trends in SGA varied by race and ethnicity, increasing only in Hispanics (RR = 1.02, 95% CI: 1.00-1.04) before the pandemic. Our study reveals an increasing prevalence of PTD and a rise in PTD < 34 wks. during the pandemic, as well as an increasing prevalence of SGA in Hispanics during the study period.

No evidence for mutations in NLRP7 and KHDC3L in women with androgenetic hydatidiform moles.

OBJECTIVE: The objective of this study was to evaluate the mutational spectrum of NLRP7 and KHDC3L (C6orf221) in women with sporadic and recurrent androgenetic complete hydatidiform moles (AnCHM) and biparental hydatidiform moles (BiHM) to address the hypothesis that autosomal recessive mutations in these genes are only or primarily associated with BiHM. METHOD: We recruited 16 women with suspected recurrent and sporadic AnCHM and five women with suspected BiHM in addition to their reproductive partners into our study. We then sequenced the coding exons of NLRP7 and KHDC3L from DNA isolated from either blood or saliva from the study subjects. RESULTS: Sequence analysis of NLRP7 and KHDC3L revealed previously described single nucleotide polymorphisms in patients with AnCHM. However, in patients with BiHM, we identified a novel homozygous mutation and a previously described intragenic duplication of exons 2 to 5 in NLRP7, both of which are likely to be disease causing. We did not identify mutations in KHDC3L in patients with either form of hydatidiform moles. CONCLUSIONS: The absence of mutations in women with AnCHM supports a role for NLRP7 or KHDC3L in BiHM only. The absence of mutations in KHDC3L in women with BiHM is consistent with its minor role in this disease compared with NLRP7, the major BiHM gene.

Sex-specific effects of nicotine exposure on developmental programming of blood pressure and vascular reactivity in the C57Bl/6J mouse.

OBJECTIVE: The objective of the study was to determine whether perinatal nicotine exposure adversely affects cardiovascular health in adulthood. STUDY DESIGN: C57Bl/6J female mice were randomized to 200 µg/mL nicotine in 2% saccharin or 2% saccharin alone from 2 weeks before breeding until weaning. Offspring weight, vital signs, and carotid artery vascular reactivity were studied. A second cohort was subjected to shaker stress on day 4 of 7 days. Selected mediators of vascular tone were evaluated by molecular studies. Student t or Mann-Whitney U test was performed for statistical analysis (significance: P < .05). RESULTS: Nicotine-exposed compared with control female offspring had significantly elevated mean blood pressure under normal and stress conditions. Nicotine females lacked heart rate elevation after stress. Nicotine males had higher mean heart rate and a blunted contractile response to phenylephrine compared with controls, without an increase in blood pressure. CONCLUSION: Perinatal nicotine exposure has an impact on the developmental programming of future cardiovascular health, with adverse effects more evident in female offspring.

Hypertensive Disorders of Pregnancy With and Without Prepregnancy Hypertension Are Associated With Incident Maternal Kidney Disease Subsequent to Delivery.

BACKGROUND: Maternal morbidity and mortality are related to prepregnancy hypertensive disease and hypertensive disorders of pregnancy (HDP) including preeclampsia (41.1% of HDP), eclampsia (1.3% of HDP), and gestational hypertension (39.9% of HDP). Less information is available on the risk of maternal kidney disease and potential racial/ethnic differences following a hypertensive condition during pregnancy. Our objective was to examine the relationships between HDP and prepregnancy hypertension with maternal incident kidney disease subsequent to delivery (up to 3, 5, and 14 years) with consideration of racial/ethnic differences. METHODS: In a retrospective cohort study, 391 838 women 12 to 49 years of age had a live birth in South Carolina between 2004 and 2016; 35.1% non-Hispanic Black (NHB) and 64.9% non-Hispanic White (NHW). Hospitalization, emergency department, and birth certificate data defined prepregnancy hypertension and HDP. Hospitalization and death certificate data identified incident kidney disease. RESULTS: 317 006 (80.8%) women experienced neither condition, 1473 (0.4%) had prepregnancy hypertension, 64 050 (16.3%) had HDP, and 9662 (2.5%) had both conditions (prepregnancy hypertension with superimposed HDP, ie, preeclampsia). Five years after delivery, incident kidney disease risk was increased for NHB and NHW women with HDP (NHB: hazard ratio, 2.30 [95% CI, 1.94-2.73]; NHW: hazard ratio, 1.97 [95% CI, 1.64-2.37]) and with both conditions (NHB: hazard ratio, 3.88 [95% CI, 3.05-4.93]; NHW: hazard ratio, 1.86 [95% CI, 1.20-2.87]) compared with counterparts with neither condition after adjustment (P value for race/ethnicity interaction=0.003). CONCLUSIONS: Increased kidney disease risk 5 years after delivery was observed for women with HDP and with both compared with neither condition, with associated risk higher in NHB than NHW women.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.

Endothelial growth factor therapy improves preeclampsia-like manifestations in a murine model induced by overexpression of sVEGFR-1.

This study examines the effects of VEGF-121 therapy in an animal model of preeclampsia induced by overexpression of soluble VEGF receptor 1 (sVEGFR-1). At day 8 of gestation, CD-1 mice were implanted with subcutaneous osmotic pumps containing either VEGF-121 or vehicle and fitted with telemetric blood pressure (BP) catheters for continuous BP monitoring (days 8-18 of gestation). On day 9, the animals in the VEGF-121 group were randomly allocated for injection with adenovirus carrying sVEGFR-1 or the murine immunoglobulin G2α Fc fragment (mFc) as virus control (Adv-sVEGFR-1; Adv-mFc). Animals in the vehicle group were injected with Adv-sVEGFR-1. On day 18, mice were euthanized, placentas and pups weighted, carotid arteries isolated, and their responses studied in vitro using a wire myograph for isometric tension recording. In mice overexpressing sVEGFR-1, treatment with VEGF-121 significantly reduced BP from days 10 to 18 of gestation compared with that of vehicle. VEGF-sVEGFR-1 animals had significantly higher vasorelaxant response to sodium nitroprusside and significantly lower contractile response to the thromboxane agonist (U-46619) compared with that of the vehicle-sVEGFR-1 mice. Phenylephrine and acetylcholine responses did not significantly vary between the VEGF-sVEGFR-1 and the vehicle-sVEGFR-1 mice. Average pup weight was significantly lower in the vehicle-sVEGFR-1 group compared with the VEGF-sVEGFR-1 and VEGF-mFc groups. In conclusion, VEGF-121 therapy attenuates vascular dysfunction and diminishes intrauterine growth abnormality in an animal model of preeclampsia induced by overexpression of sVEGFR-1. Modulation of VEGF pathway turns into a promising therapeutic approach of preeclampsia.

Predictors of local malaria outbreaks: an approach to the development of an early warning system in Colombia.

Risk factor surveillance is a complementary tool of morbidity and mortality surveillance that improves the likelihood that public health interventions are implemented in a timely fashion. The aim of this study was to identify population predictors of malaria outbreaks in endemic municipalities of Colombia with the goal of developing an early warning system for malaria outbreaks. We conducted a multiple-group, exploratory, ecological study at the municipal level. Each of the 290 municipalities with endemic malaria that we studied was classified according to the presence or absence of outbreaks. The measurement of variables was based on historic registries and logistic regression was performed to analyse the data. Altitude above sea level [odds ratio (OR) 3.65, 95% confidence interval (CI) 1.34-9.98], variability in rainfall (OR 1.85, 95% CI 1.40-2.44) and the proportion of inhabitants over 45 years of age (OR 0.17, 95% CI 0.08-0.38) were factors associated with malaria outbreaks in Colombian municipalities. The results suggest that environmental and demographic factors could have a significant ability to predict malaria outbreaks on the municipal level in Colombia. To advance the development of an early warning system, it will be necessary to adjust and standardise the collection of required data and to evaluate the accuracy of the forecast models.

Does information available at delivery improve the accuracy of predicting vaginal birth after cesarean? Validation of the published models in an independent patient cohort.

We sought to validate a proposed vaginal birth after cesarean (VBAC) prediction model that includes variables available "at or close to delivery" and compare its accuracy to one that only uses variables available at "entry to care." We performed a retrospective cohort study of term pregnant women with a vertex singleton gestation attempting a trial of labor (TOL) after a single prior low transverse cesarean delivery. VBAC rates, predicted using the "close to delivery" model, were partitioned into deciles. The observed VBAC rate in each partition was compared with the predicted one. The accuracy of the two models was compared using the receiver operating characteristics curve. The predicted VBAC probability was higher in patients who had VBAC compared with those who failed a TOL (median [interquartile range]: 74.9% [59.6 to 86.1] versus 48.6% [35.4 to 66.7]; P < 0.001). The correlation between the observed and predicted VBAC rates was high (R = 0.98; P < 0.001). In the subset of patients who had the complete set of variables available for the two models (N = 490), the "close to delivery" model was more accurate. We validated the proposed VBAC prediction model in an independent cohort. Incorporating information available at delivery improves its accuracy.

Incident Heart Failure Within the First and Fifth Year after Delivery Among Women With Hypertensive Disorders of Pregnancy and Prepregnancy Hypertension in a Diverse Population.

Background Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension are associated with increased morbidity and mortality for the mother. Our aim was to investigate the relationships between HDP and pre-pregnancy hypertension with maternal heart failure (HF) within 1 and 5 years of delivery and to examine racial/ethnic differences. Methods and Results We conducted a retrospective cohort study in South Carolina (2004-2016) involving 425 649 women aged 12 to 49 years (58.9% non-Hispanic White [NHW], 31.5% non-Hispanic Black [NHB], 9.6% Hispanic) with a live, singleton birth. Incident HF was defined by hospital/emergency department visit and death certificate data. Pre-pregnancy hypertension and HDP (preeclampsia, eclampsia, or gestational hypertension) were based on hospitalization/emergency department visit and birth certificate data (i.e., gestational hypertension for HDP). The 425 649 women had pre-pregnancy hypertension without superimposed HDP (pre-pregnancy hypertension alone; 0.4%), HDP alone (15.7%), pre-pregnancy hypertension with superimposed HDP (both conditions; 2.2%), or neither condition in any pregnancy (81.7%). Incident HF event rates per 1000 person-years were higher in NHB than NHW women with HDP (HDP: 2.28 versus 0.96; both conditions: 4.30 versus 1.22, respectively). After adjustment, compared with women with neither condition, incident HF risk within 5 years of delivery was increased for women with pre-pregnancy hypertension (HR,2.55, 95% CI: 1.31-4.95), HDP (HR,4.20, 95% CI: 3.66-4.81), and both conditions (HR,5.25, 95% CI: 4.24-6.50). Conclusions Women with HDP and pre-pregnancy hypertension were at higher HF risk (highest for superimposed preeclampsia) within 5 years of delivery. NHB women with HDP had higher HF risk than NHW women, regardless of pre-pregnancy hypertension.

Maternal Coronary Heart Disease, Stroke, and Mortality Within 1, 3, and 5 Years of Delivery Among Women With Hypertensive Disorders of Pregnancy and Pre-Pregnancy Hypertension.

Background Pre-pregnancy hypertension and hypertensive disorders of pregnancy (HDP; preeclampsia, eclampsia, gestational hypertension) are major health risks for maternal morbidity and mortality. However, it is unknown if racial/ethnic differences exist. We aimed to determine the impact of HDP and pre-pregnancy hypertension on maternal coronary heart disease, stroke, and mortality risk ≤1, 3, and 5 years post-delivery and by race/ethnicity ≤5 years. Methods and Results This retrospective cohort study included women aged 12 to 49 years with a live, singleton birth between 2004 to 2016 (n=254 491 non-Hispanic White; n=137 784 non-Hispanic Black; n=41 155 Hispanic). Birth and death certificates and International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification (ICD-9-CM and ICD-10-CM) diagnosis codes in hospitalization/emergency department visit data defined HDP, pre-pregnancy hypertension, incident coronary heart disease and stroke, and all-cause mortality. During at least 1 pregnancy of the 433 430 women, 2.3% had pre-pregnancy hypertension with superimposed HDP, 15.7% had no pre-pregnancy hypertension with HDP, and 0.4% had pre-pregnancy hypertension without superimposed HDP, whereas 81.6% had neither condition. Maternal deaths from coronary heart disease, stroke, and all causes totaled 2136. Within 5 years of delivery, pre-pregnancy hypertension, and HDP were associated with all-cause mortality (hazard ratio [HR], 2.21; 95% CI, 1.61-3.03), incident coronary heart disease (HR, 3.79; 95% CI, 3.09-4.65), and incident stroke (HR, 3.10; 95% CI, 2.09-4.60). HDP alone was related to all outcomes. Race/ethnic differences were observed for non-Hispanic Black and non-Hispanic White women, respectively, in the associations of pre-pregnancy hypertension and HDP with all-cause mortality within 5 years of delivery (HR, 2.34 [95% CI, 1.58-3.47]; HR, 2.11 [95% CI, 1.23-3.65]; P interaction=0.001). Conclusions Maternal cardiovascular outcomes including mortality were increased ≤5 years post-delivery in HDP, pre-pregnancy hypertension, or pre-pregnancy hypertension with superimposed HDP. The race/ethnic interaction for all-cause mortality ≤5 years of delivery warrants further research.

Genetic markers for preeclampsia in Peruvian women.

BACKGROUND: Preeclampsia is a multiorgan disorder associated with maternal and perinatal morbi-mortality. In Peru, incidence is 10% and accounts for 22% of maternal deaths. Genome and genetic epidemiological studies have found an association between preeclampsia and genetic polymorphisms. OBJECTIVE: To determine the association of the vascular endothelial growth factor (VEGF) +936 C/T and +405 G/C, interleukine-6 (IL-6) -174 G/C, IL-1ß-511 C/T, Apo A-1-75 G/A, Apo B-100 2488 C/T (Xbal) polymorphisms with preeclampsia in pregnant Peruvian women. METHODS: Were included preeclamptic and healthy (control) pregnant women. Maternal blood samples were subjected to DNA extraction, and molecular genetic analysis was conducted using the PCR-RFLP technique and following a specific protocol for each gene. Allele and genotypic frequencies in the cases and controls were compared. RESULTS: No association was found between the VEGF+936C/T and VEGF+405 polymorphisms and preeclampsia. The frequencies of the GG genotypes and the G allele of the -174 G/C polymorphism in the IL6 gene in preeclamptic and controls showed significant differences, with higher frequencies in cases. For the -511 C/T polymorphism of the IL-1ß gene, no significant differences were found in the frequencies of TT genotypes compared with CT+CC. The genotypes and alleles of the Apo-A1-75 G/A and Apo-B100 Xbal variants showed no significant differences between cases and controls. CONCLUSION: No association was found between the studied genetic markers and preeclampsia. However, in the -174G/C polymorphism of the IL-6 gene, significant differences were found mainly in the GG genotype and G allele.

Does Resolution 8430 of 1993 respond to the current needs of ethics in health research with human beings in Colombia? / ¿Responde la Resolución 8430 de 1993 a las necesidades actuales de la ética de la investigación en salud con seres humanos en Colombia?

Verifying the compliance with the ethical principles of health research legitimizes its exercise in the eyes of the society and allows for the resolution of ethical dilemmas that emerge from new research interests and methods. Resolution 8430 of 1993 is one of the main ethical guidelines governing health research on human beings in Colombia. Considering that the resolution has not been revised or updated since its promulgation it becomes necessary to evaluate its current validity and adequacy to address the potential ethical dilemmas in the existing country's health research. Some gaps, contradictions, and aspects that require a deep review are detailed in this paper from a wide conception of health research areas and methods. After discussing the main weaknesses and inaccuracies, some alternatives are proposed to adjust the resolution to the present needs in health research with human beings.

La verificación del cumplimiento de los principios éticos en la investigación en salud legitima su ejercicio ante la sociedad y posibilita la resolución de dilemas éticos frente a nuevos intereses y métodos de investigación. En Colombia, la Resolución 8430 de 1993 es una de las principales pautas éticas que regulan la investigación en salud. Dado que no ha sido revisada ni actualizada desde su adopción, se hace necesario valorar su vigencia y suficiencia para abordar los potenciales dilemas éticos que se plantean actualmente en la investigación en salud en el país. En este contexto, se detallan algunos vacíos y contradicciones, así como aspectos que requieren de una revisión profunda, a partir de una concepción amplia de las áreas y los métodos de investigación en salud. Tras discutir las principales falencias e imprecisiones, se proponen alternativas para que la Resolución responda a las necesidades actuales del país frente a la ética en investigación en salud con seres humanos.