Eduardo Bergel

Calcium supplementation to prevent hypertensive disorders of pregnancy.

Abstract Background. Calcium supplementation has been reported to reduce blood pressure in pregnant and nonpregnant women. We undertook this prospective study to determine the effect of calcium supplementation on the incidence of hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) and to determine the value of urinary calcium levels as a predictor of the response. Methods. We studied 1194 nulliparous women who were in the 20th week of gestation at the beginning of the study. The women were randomly assigned to receive 2 g per day of elemental calcium in the form of calcium carbonate (593 women) or placebo (601 women). Urinary excretion of calcium and creatinine was measured before calcium supplementation was begun. The women were followed to the end of their pregnancies, and the incidence of hypertensive disorders of pregnancy was determined. Results. The rates of hypertensive disorders of pregnancy were lower in the calcium group than in the placebo group (9.8 percent vs. 14.8...

Maternal BMI and preterm birth: A systematic review of the literature with meta-analysis

Objectives. To examine the association between high prepregnancy maternal body mass index (BMI) and the risk of preterm birth (PTB). Methods. A systematic review of the literature. We included cohorts and case-control studies published since 1968 that examined the association between BMI and PTB of all types, spontaneous (s), elective and with ruptured membranes (PPROM) in three gestational age categories: general (<37 weeks), moderate (32–36 weeks) and very (<32 weeks) PTB. Results. 20,401 citations were screened and 39 studies (1,788,633 women) were included. Preobese (BMI, 25–29.9) and obese I (BMI, 30–34.9) women have a reduced risk for sPTB: AOR = 0.85 (95% CI: 0.80–0.92) and 0.83 (95% CI: 0.75–0.92), respectively. Their risk for moderate PTB was 1.20 (95% CI: 1.04–1.38) and 1.60 (95% CI: 1.32–1.94), respectively. Obese II women (BMI, 35–40) have an increased risk for PTB in general (AOR = 1.33, 95% CI: 1.12–1.57) moderate (AOR = 2.43, 95% CI: 1.46–4.05) and very PTB (AOR = 1.96, 95% CI: 1.66–2.31). Obese III women (BMI > 40) have an even higher risk for very PTB (AOR = 2.27, 95%CI: 1.76–2.94). High BMI does not modify the risk for PPROM and increases the risk for elective PTB. Conclusions. High maternal BMI may have different effects on different types of PTB.

Active management of the third stage of labour with and without controlled cord traction: a randomised, controlled, non-inferiority trial

BACKGROUND Active management of the third stage of labour reduces the risk of post-partum haemorrhage. We aimed to assess whether controlled cord traction can be omitted from active management of this stage without increasing the risk of severe haemorrhage. METHODS We did a multicentre, non-inferiority, randomised controlled trial in 16 hospitals and two primary health-care centres in Argentina, Egypt, India, Kenya, the Philippines, South Africa, Thailand, and Uganda. Women expecting to deliver singleton babies vaginally (ie, not planned caesarean section) were randomly assigned (in a 1:1 ratio) with a centrally generated allocation sequence, stratified by country, to placental delivery with gravity and maternal effort (simplified package) or controlled cord traction applied immediately after uterine contraction and cord clamping (full package). After randomisation, allocation could not be concealed from investigators, participants, or assessors. Oxytocin 10 IU was administered immediately after birth with cord clamping after 1-3 min. Uterine massage was done after placental delivery according to local policy. The primary (non-inferiority) outcome was blood loss of 1000 mL or more (severe haemorrhage). The non-inferiority margin for the risk ratio was 1·3. Analysis was by modified intention-to-treat, excluding women who had emergency caesarean sections. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN 12608000434392. FINDINGS Between June 1, 2009, and Oct 30, 2010, 12,227 women were randomly assigned to the simplified package group and 12,163 to the full package group. After exclusion of women who had emergency caesarean sections, 11,861 were in the simplified package group and 11,820 were in the full package group. The primary outcome of blood loss of 1000 mL or more had a risk ratio of 1·09 (95% CI 0·91-1·31) and the upper 95% CI limit crossed the pre-stated non-inferiority margin. One case of uterine inversion occurred in the full package group. Other adverse events were haemorrhage-related. INTERPRETATION Although the hypothesis of non-inferiority was not met, omission of controlled cord traction has very little effect on the risk of severe haemorrhage. Scaling up of haemorrhage prevention programmes for non-hospital settings can safely focus on use of oxytocin. FUNDING United States Agency for International Development and UN Development Programme/UN Population Fund/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research.

Perinatal risk in singleton pregnancies after in vitro fertilization

OBJECTIVE To assess perinatal risks to singleton births after in vitro fertilization (IVF) versus spontaneous conception. DESIGN Cross-sectional. SETTING A 2006 registry database of the Japan Society of Obstetrics and Gynaecology (JSOG) capturing 5.8% of total births. PATIENT(S) 53,939 singleton births from spontaneous conceptions and 1,408 singletons after IVF. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Perinatal death, low-birth weight (LBW), small for gestational age (SGA), congenital malformation, and sex ratio assessment based on singleton birth cases versus singleton live-born cases. RESULT(S) In this study, IVF may include intracytoplasmic sperm injection (ICSI), gamete intrafallopian transfer, or IVF followed by zygote intrafallopian transfer. In crude and adjusted analysis, perinatal death, SGA, congenital malformation, and sex ratio were not statistically significantly associated with IVF. The LBW rates were statistically significantly higher in IVF pregnancies, but the association statistically significantly decreased after adjusting for confounding factors. Placental previa, a maternal outcome, was found to be statistically significantly higher in IVF pregnancies. CONCLUSION(S) No evidence was implicated IVF procedures as dramatically increasing the adjusted risk of perinatal death, LBW, SGA, congenital malformation, or sex ratio when compared with spontaneous conceptions. However, because of sample size limitations, the study cannot exclude small to moderate increases in perinatal deaths or congenital malformations.

TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization

While 30%-70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial. Here, we evaluated the interaction between TLR4 and environmental factors in RSV disease and defined the immune mediators associated with severe illness. Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS. RSV-infected infants with severe disease exhibited a high GATA3/T-bet ratio, which manifested as a high IL-4/IFN-γ ratio in respiratory secretions. The IL-4/IFN-γ ratio present in infants with severe RSV is indicative of Th2 polarization. Murine models of RSV infection confirmed that LPS exposure, Tlr4 genotype, and Th2 polarization influence disease phenotypes. Together, the results of this study identify environmental and genetic factors that influence RSV pathogenesis and reveal that a high IL-4/IFN-γ ratio is associated with severe disease. Moreover, these molecules should be explored as potential targets for therapeutic intervention.

What does an elevated mean arterial pressure in second half of pregnancy predict —Gestational hypertension or preeclampsia?

OBJECTIVE The purpose of this study was to determine the predictive value of elevated mean arterial pressure in the second half of pregnancy for both preeclampsia and gestational hypertension. STUDY DESIGN This was a cohort of 588 nulliparous pregnant women studied prospectively from the twentieth week until delivery. Mean arterial pressure was obtained by means of a random-zero sphygmomanometer at 20, 26, and 31 weeks of gestation. The best cutoff point for the determination of predictive values was established by a receiver-operator characteristic curve. RESULTS Patterns of mean arterial pressure throughout pregnancy were different between preeclamptic and gestational hypertensive women. Receiver-operator characteristic curves for mean arterial pressure showed better predictive capacity for gestational hypertension than for preeclampsia. Sensitivity of mean arterial pressure to predict preeclampsia ranged between 39% and 48%, whereas for prediction of gestational hypertension it varied from 72% to 92%. Specificities for both groups were moderate (60% to 86%). Positive predictive values were low for all groups (5% to 33%). CONCLUSION Elevated mean arterial pressure in the second half of pregnancy is a good predictor of gestational hypertension but is a poor predictor of preeclampsia.

Differential Gender Response to Respiratory Infections and to the Protective Effect of Breast Milk in Preterm Infants

OBJECTIVE. The protective role of breastfeeding against severe acute lung disease in infants is well established, but its mechanism is unclear. Most hypotheses assume that breastfeeding confers similar passive protection to every infant; however, a few observations have suggested that the benefits of breast milk against severe lung disease may differ according to gender. The objective of this study was to determine whether the effect of breastfeeding on susceptibility to severe acute lung disease among infants at high risk is different for girls and boys. METHODS. A cohort was analyzed prospectively by use of 2 different strategies: (1) predictors of first episode of rehospitalization by univariate and multivariate analyses using robust Poisson regression and (2) mean number of rehospitalizations between groups using multiple regression negative binomial models. RESULTS. A total of 119 high-risk, very low birth weight infants were enrolled. Breast milk protected girls but not boys against severe acute lung disease. The interaction between breastfeeding and gender was clinically and statistically significant, even after adjustment for variables that can affect severity of acute lung disease. Disease was most severe in formula-fed girls (versus formula-fed boys). CONCLUSIONS. Breastfeeding decreased the risk for severe acute lung disease in girls but not in boys. These findings suggest that breast milk protection is not universally conferred by passive transfer of humoral immunity (which should be gender indifferent), show that respiratory symptoms may be amenable to nonspecific modulation, and identify nonbreastfed preterm infant girls as an at-risk group for severe acute lung disease.

The measurement of diastolic blood pressure during pregnancy: Which Korotkoff phase should be used?

OBJECTIVE The aim of this study was to compare the two Korotkoff phases, to estimate diastolic blood pressure during pregnancy. STUDY DESIGN A cohort of 1194 nulliparous pregnant women were followed up prospectively from the twentieth week of pregnancy until delivery. Blood pressure measurements were obtained with random-zero sphygmomanometers at 20, 23, 25, 27, 31, and 35 weeks and then weekly until delivery. After 10 minutes of rest five blood pressure measurements were obtained in each position: supine, lateral, and seated. Korotkoff phases IV and V were obtained in each measurement. RESULTS The frequency of 0 values was always < 0.5% (n = 10,501 in each time and position). Mean differences between both phases throughout pregnancy fluctuates around 6 mm Hg. Minor differences (mean 3.7 mm Hg) without outlier values were observed in women with diastolic hypertension. Phase 5 showed a better association with other outcome variables related to hypertension, such as proteinuria, intrauterine growth retardation, and hyperuricemia. CONCLUSION Considering that phase 5 is easier to obtain, its use implies very few 0 values, that the difference between the two Korotkoff phases is around 6 mm Hg, and that the association with hypertension-related complications is similar to that of phase 4.

Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol

BackgroundPreterm birth is a major cause of neonatal mortality, responsible for 28% of neonatal deaths overall. The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in resource rich environments. The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital settings in developed countries with high utilization is well established, yet they are not routinely used in developing countries. The impact of increasing antenatal steroid use in hospital or community settings with low utilization rates and high infant mortality among premature infants due to lack of specialized services has not been well researched. There is currently no clear evidence about the safety of antenatal corticosteroid use for community-level births.MethodsWe hypothesize that a multi country, two-arm, parallel cluster randomized controlled trial to evaluate whether a multifaceted intervention to increase the use of antenatal corticosteroids, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, will reduce neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six countries. 102 clusters in Argentina, Guatemala, Kenya, India, Pakistan, and Zambia will be randomized, and around 60,000 women and newborns will be enrolled. Kits containing vials of dexamethasone, syringes, gloves, and instructions for administration will be distributed. Improving the identification of women at high risk of preterm birth will be done by (1) diffusing recommendations for antenatal corticosteroids use to health providers, (2) training health providers on identification of women at high risk of preterm birth, (3) providing reminders to health providers on the use of the kits, and (4) using a color-coded tape to measure uterine height to estimate gestational age in women with unknown gestational age. In both intervention and control clusters, health providers will be trained in essential newborn care for low birth weight babies. The primary outcome is neonatal mortality at 28 days of life in preterm infants.Trial registrationClinicalTrials.gov. Identifier: NCT01084096

Non-pneumatic anti-shock garment (NASG), a first-aid device to decrease maternal mortality from obstetric hemorrhage: a cluster randomized trial.

Background Obstetric hemorrhage is the leading cause of maternal mortality. Using a cluster randomized design, we investigated whether application of the Non-pneumatic Anti-Shock Garment (NASG) before transport to referral hospitals (RHs) from primary health care centers (PHCs) decreased adverse outcomes among women with hypovolemic shock. We hypothesized the NASG group would have a 50% reduction in adverse outcomes. Methods and Findings We randomly assigned 38 PHCs in Zambia and Zimbabwe to standard obstetric hemorrhage/shock protocols or the same protocols plus NASG prior to transport. All women received the NASG at the RH. The primary outcomes were maternal mortality; severe, end-organ failure maternal morbidity; and a composite mortality/morbidity outcome, which we labeled extreme adverse outcome (EAO). We also examined whether the NASG contributed to negative side effects and secondary outcomes. The sample size for statistical power was not reached; of a planned 2400 women, 880 were enrolled, 405 in the intervention group. The intervention was associated with a non-significant 46% reduced odds of mortality (OR 0.54, 95% CI 0.14–2.05, p = 0.37) and 54% reduction in composite EAO (OR 0.46, 95% CI 0.13–1.62, p = 0.22). Women with NASGs recovered from shock significantly faster (HR 1.25, 95% CI 1.02–1.52, p = 0.03). No differences were observed in secondary outcomes or negative effects. The main limitation was small sample size. Conclusions Despite a lack of statistical significance, the 54% reduced odds of EAO and the significantly faster shock recovery suggest there might be treatment benefits from earlier application of the NASG for women experiencing delays obtaining definitive treatment for hypovolemic shock. As there are no other tools for shock management outside of referral facilities, and no safety issues found, consideration of NASGs as a temporizing measure during delays may be warranted. A pragmatic study with rigorous evaluation is suggested for further research. Trial Registration ClinicalTrials.gov NCT00488462