To describe the methods for assigning the cause of death for stillbirths enrolled in the Stillbirth Collaborative Research Network (SCRN).
A complete evaluation, including postmortem examination, placental pathology, medical record abstraction, and maternal interview was available on 512 stillbirths among 500 women. These 512 stillbirths were evaluated for cause of death using the definitions outlined in this report. Using the best available evidence, SCRN investigators developed a new methodology to assign the cause of death of stillbirths using clinical, postmortem, and placental pathology data. This new tool, designated the Initial Causes of Fetal Death, incorporates known causes of death and assigns them as possible or probable based on strict diagnostic criteria, derived from published references and pathophysiologic sequences that lead to stillbirth.
Six broad categories of causes of death are accounted for, including maternal medical conditions; obstetric complications; maternal or fetal hematologic conditions; fetal genetic, structural, and karyotypic abnormalities; placental infection, fetal infection, or both; and placental pathologic findings. Isolated histologic chorioamnionitis and small for gestational age were not considered causes of death.
A new system, Initial Causes of Fetal Death, to assign cause of death in stillbirths was developed by the SCRN investigators for use in this study but has broader applicability. Initial Causes of Fetal Death is a standardized method to assign probable and possible causes of death of stillbirths based on information routinely collected during prenatal care and the clinical evaluation of fetal death.
Fetal and neonatal mortality rates in low-income countries are at least 10-fold greater than in high-income countries. These differences have been related to poor access to and poor quality of obstetric and neonatal care.
This trial tested the hypothesis that teams of health care providers, administrators and local residents can address the problem of limited access to quality obstetric and neonatal care and lead to a reduction in perinatal mortality in intervention compared to control locations. In seven geographic areas in five low-income and one middle-income country, most with high perinatal mortality rates and substantial numbers of home deliveries, we performed a cluster randomized non-masked trial of a package of interventions that included community mobilization focusing on birth planning and hospital transport, community birth attendant training in problem recognition, and facility staff training in the management of obstetric and neonatal emergencies. The primary outcome was perinatal mortality at ≥28 weeks gestation or birth weight ≥1000 g.
Despite extensive effort in all sites in each of the three intervention areas, no differences emerged in the primary or any secondary outcome between the intervention and control clusters. In both groups, the mean perinatal mortality was 40.1/1,000 births (P = 0.9996). Neither were there differences between the two groups in outcomes in the last six months of the project, in the year following intervention cessation, nor in the clusters that best implemented the intervention.
This cluster randomized comprehensive, large-scale, multi-sector intervention did not result in detectable impact on the proposed outcomes. While this does not negate the importance of these interventions, we expect that achieving improvement in pregnancy outcomes in these settings will require substantially more obstetric and neonatal care infrastructure than was available at the sites during this trial, and without them provider training and community mobilization will not be sufficient. Our results highlight the critical importance of evaluating outcomes in randomized trials, as interventions that should be effective may not be.
Stillbirth; Neonatal mortality; Maternal mortality; Emergency obstetric care
To describe the staffing and availability of medical equipment and medications and the performance of procedures at health facilities providing maternal and neonatal care at African, Asian, and Latin American sites participating in a multicenter trial to improve emergency obstetric/neonatal care in communities with high maternal and perinatal mortality.
In 2009, prior to intervention, we surveyed 136 hospitals and 228 clinics in 7 sites in Africa, Asia, and Latin America regarding staffing, availability of equipment/ medications, and procedures including cesarean section.
The coverage of physicians and nurses/midwives was poor in Africa and Latin America. In Africa, only 20% of hospitals had full-time physicians. Only 70% of hospitals in Africa and Asia had performed cesarean sections in the last 6 months. Oxygen was unavailable in 40% of African hospitals and 17% of Asian hospitals. Blood was unavailable in 80% of African and Asian hospitals.
Assuming that adequate facility services are necessary to improve pregnancy outcomes, it is not surprising that maternal and perinatal mortality rates in the areas surveyed are high. The data presented emphasize that to reduce mortality in these areas, resources that result in improved staffing and sufficient equipment, supplies, and medication, along with training, are required.
emergency obstetric and neonatal care; developing countries; perinatal mortality
There are few studies of the association between placental malaria (PM) and mother-to-child transmission (MTCT) of human immunodeficiency virus-1 (HIV-1), and the results of published studies are inconsistent. To determine the association between PM and MTCT of HIV-1, we performed a secondary analysis of data from a clinical trial of antibiotics to reduce chorioamnionitis. Data regarding 1,662 HIV-1–infected women with live born singleton and first-born twin infants with information regarding PM and infant HIV-1 infection status at birth were analyzed. At the time of the study, women did not have access to antiretroviral drugs for treatment of acquired immunodeficiency syndrome but had received nevirapine prophylaxis to reduce the risk of MTCT of HIV-1. Placental malaria was not associated with the infant HIV-1 infection status at birth ( P = 0.67). Adjustment for maternal plasma viral load and CD4+ cell count did not change these results (odds ratio = 1.06, 95% confidence interval = 0.51–2.20, P = 0.87). Placental malaria was more likely to be related to HIV-1 infection at birth among women with low viral load at baseline (P for interaction = 0.08). In conclusion, PM was not associated with infant HIV-1 infection status at birth. The interaction of maternal plasma viral load, PM, and MTCT of HIV-1 warrants further studies.
To implement a vital statistics registry system to register pregnant women and document birth outcomes in the Global Network for Women’s and Children’s Health Research sites in Asia, Africa, and Latin America.
The Global Network sites began a prospective population-based pregnancy registry to identify all pregnant women and record pregnancy outcomes up to 42 days post-delivery in more than 100 defined low-resource geographic areas (clusters). Pregnant women were registered during pregnancy, with 42-day maternal and neonatal follow-up recorded—including care received during the pregnancy and postpartum periods. Recorded outcomes included stillbirth, neonatal mortality, and maternal mortality rates.
In 2010, 72 848 pregnant women were enrolled and 6-week follow-up was obtained for 97.8%. Across sites, 40.7%, 24.8%, and 34.5% of births occurred in a hospital, health center, and home setting, respectively. The mean neonatal mortality rate was 23 per 1000 live births, ranging from 8.2 to 48.5 per 1000 live births. The mean stillbirth rate ranged from 13.7 to 54.4 per 1000 births.
The registry is an ongoing study to assess the impact of interventions and trends regarding pregnancy outcomes and measures of care to inform public health.
Maternal mortality; Neonatal mortality; Perinatal mortality; Pregnancy; Registry; Stillbirth
We sought to determine whether midtrimester amniotic fluid levels of matrix metalloproteinase-8 were associated with subsequent preterm premature rupture of membranes.
We conducted a case-control study examining 57 asymptomatic women who underwent genetic amniocentesis from 14 to 21 weeks’ gestation and subsequently had preterm premature rupture of membranes (<35 wk) and 58 women with subsequent term delivery. Measurement of total matrix metalloproteinase-8 level in amniotic fluid was conducted using a commercially available enzyme-linked immunosorbent assay and association with preterm birth due to preterm premature rupture of membranes was assessed.
The overall distribution of matrix metalloproteinase-8 concentrations was similar in women who had preterm premature rupture of membranes and term controls (median 2.39 ng/mL, 25th to 75th percentile 1.1-10.1 vs 2.37 ng/mL, 25th to 75th percentile 1.5-4.7, P = .94). However, 26% of women who had preterm premature rupture of membranes had a matrix metalloproteinase-8 concentration above the 90th percentile (8.7 ng/mL), compared with only 10% of term controls (odds ratio 3.1, 95% CI 1.1-8.7; P = .03). Elevated matrix metalloproteinase-8 remained associated with preterm premature rupture of membranes after adjustment for maternal age, race, parity, gestational age, and year of amniocentesis (odds ratio 3.4, 95% CI 1.2-9.9; P = .03).
The overall distribution of midtrimester amniotic fluid matrix metalloproteinase-8 levels did not differ between women who had preterm premature rupture of membranes and those delivered at term. However, marked elevations of midtrimester amniotic fluid matrix metalloproteinase-8 were highly associated with subsequent preterm premature rupture of membranes, suggesting that the pathophysiologic processes that contribute to preterm premature rupture of membranes may begin in early pregnancy.
Matrix metalloproteinase-8; Premature rupture of membranes; Intrauterine inflammation; Preterm birth
Although cytokines play a dual role in the developing neurologic system and in prenatal immune reactions, relations between fetal cytokine levels and child intellectual development remain unknown. The authors investigated associations between umbilical cord serum cytokine concentrations and intellectual outcomes in 369 children within a prospective cohort study, the Eunice Kennedy Shriver National Institute of Child Health and Human Development-University of Alabama Infant Growth Study (1985–1988). Concentrations of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukins 4, 10, and 12p70 were determined. The Wechsler Preschool and Primary Scale of Intelligence–Revised was administered at age 5 years, producing verbal and performance intelligence quotients (VIQ and PIQ); associations with each cytokine were evaluated using linear and logistic regression. Log-unit increases in IFN-γ (adjusted odds ratio (aOR) = 0.67, 95% confidence interval (CI): 0.46, 0.98) and interleukin-12p70 (aOR = 0.43, 95% CI: 0.21, 0.87) were inversely associated with low PIQ (score <70). One log-unit increase in TNF-α was associated with a reduced odds ratio for low VIQ (score <70) among preterm children (aOR = 0.11, 95% CI: 0.01, 0.94) and an elevated odds ratio for low VIQ among small-for-gestational-age children (aOR = 3.96, 95% CI: 0.99, 15.9). IFN-γ, which is involved in neurogenesis and perinatal adaptive immunity, may be related to fetal neurologic development overall, while TNF-α may be a marker of intellectual development in vulnerable subgroups.
child development; cohort studies; cytokines; intelligence tests; interferon-gamma; tumor necrosis factor-alpha; umbilical cord
The Stillbirth Collaborative Research Network (SCRN) has conducted a multisite, population-based, case-control study, with prospective enrollment of stillbirths and live births at the time of delivery. This paper describes the general design, methods, and recruitment experience. The SCRN attempted to enroll all stillbirths and a representative sample of live births occurring to residents of pre-defined geographic catchment areas delivering at 59 hospitals associated with five clinical sites. Live births <32 weeks gestation and women of African descent were oversampled. The recruitment hospitals were chosen to ensure access to at least 90% of all stillbirths and live births to residents of the catchment areas. Participants underwent a standardized protocol including maternal interview, medical record abstraction, placental pathology, biospecimen testing, and, in stillbirths, postmortem examination. Recruitment began in March 2006 and was completed in September 2008 with 663 women with a stillbirth and 1932 women with a live birth enrolled, representing 69% and 63%, respectively, of the women identified. Additional surveillance for stillbirth continued through June 2009 and a follow-up of the case-control study participants was completed in December 2009.
Among consenting women, there were high consent rates for the various study components. For the women with stillbirth, 95% agreed to maternal interview, chart abstraction, and placental pathologic examination; 91% of the women with live birth agreed to all of these components. Additionally, 84% of the women with stillbirth agreed to a fetal postmortem examination. This comprehensive study is poised to systematically study a wide range of potential causes of, and risk factors for, stillbirth and to better understand the scope and incidence of the problem.
Ninety-eight percent of the 3.7 million neonatal deaths and 3.3 million stillbirths per year occur in developing countries, and evaluation of community-based interventions is needed.
Using a train-the-trainer model, local instructors trained birth attendants from rural communities in six countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia) in the World Health Organization Essential Newborn Care course (routine neonatal care, resuscitation, thermoregulation, breastfeeding, kangaroo care, care of the small baby, and common illnesses), and in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (in depth basic resuscitation), except in Argentina.
The Essential Newborn Care intervention was assessed with a before and after design (N=57, 643). The Neonatal Resuscitation Program intervention was assessed as a cluster randomized controlled trial (N=62,366). The primary outcome was 7-day neonatal mortality.
The 7-day follow-up rate was 99.2%. Following Essential Newborn Care training, there was no significant reduction from baseline in all-cause 7-day neonatal (RR 0.99; CI 0.81, 1.22) or perinatal mortality; there was a significant reduction in the stillbirth rate (RR 0.69; CI 0.54, 0.88; p<0.01). Seven-day neonatal mortality, stillbirth, and perinatal mortality were not reduced in clusters randomized to Neonatal Resuscitation Program training as compared with control clusters.
Seven-day neonatal mortality did not decrease following the introduction of Essential Newborn Care training of community-based birth attendants, although the rate of stillbirths was reduced following this intervention. Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates. (clinicaltrials.gov number, NCT00136708).
neonatal mortality; perinatal mortality; developing countries; health systems; effectiveness
To correlate maternal and cord blood cytokine and ICAM-1 levels with antibiotic exposure and perinatal outcomes after conservatively managed preterm PROM
Conservatively managed women with preterm PROM at 24–32 weeks had blood sampling at randomization (N=222) and delivery (N=121). Plasma from these, and umbilical cord blood (N=196), was stored at −70C. IL-6, IL-10, G-CSF, TNF-alpha and ICAM-1 levels were assessed for associations with antibiotic treatment, latency, amnionitis, neonatal sepsis, pneumonia, and composite neonatal morbidity.
Cord blood IL-6 and G-CSF were higher than maternal levels. Antibiotic treatment lowered only maternal G-CSF (p=0.01). Elevated maternal cytokine levels were associated with delivery within seven days and with development of chorioamnionitis. All umbilical cord blood markers were increased with amnionitis (p≤0.01 for each). No maternal marker was associated with neonatal morbidities. Cord G-CSF and IL-6 were increased with neonatal sepsis within 72 hours of birth (p=0.004 for both), and with composite neonatal morbidity; (p=0.001 and 0.002, respectively). Maternal and umbilical cord cytokine levels demonstrated low predictive values for perinatal outcomes.
Umbilical cord blood cytokine values are higher than maternal levels, suggesting significant fetal/placental contribution. Maternal and umbilical cord cytokine levels are not adequately predictive to be used clinically.
cytokines; tumor necrosis factor-alpha; granulocyte colony stimulating factor; intercellular adhesion molecule-1; premature rupture of membranes; PROM
Objective. To identify maternal and early childhood risk factors for obesity and overweight among children at age 5 in the state of Alabama. Methods. We recruited 740 mothers during early pregnancy from University of Alabama Prenatal Clinics in a prospective cohort study and followed them throughout pregnancy. We followed their children from birth until 5 years of age. The main outcome measure was obesity (BMI for age and sex ≥ 95th percentile) at 5 years of age. We used poisson regression with robust variance estimation to compute risk ratio (RR). Results. At the 5th year of followup, 71 (9.6%) of the children were obese and 85 (11.5%) were overweight (BMI ≥ 85th–<95th percentile). In multivariable analysis, maternal prepregnancy overweight (RR: 2.30, 95% CI: 1.29–4.11) and obesity (RR: 2.53, 95% CI: 1.49–4.31), and child's birth weight >85th percentile (RR: 2.04, 95% CI: 1.13–3.68) were associated with childhood obesity. Maternal prepregnancy BMI, birth weight, and maternal smoking were associated with the child being overweight 1–12 cigarettes/day versus 0 cigarettes/day (RR: 1.40, 95% CI: 1.02–1.91). Conclusion. Children of overweight and obese mothers, and children with higher birth weight, are more likely to be obese and overweight at age 5. Maternal smoking 1–12 cigarettes per day is associated with the child being overweight.
Preterm 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.
We 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.
ClinicalTrials.gov. Identifier: NCT01084096
Neonatal mortality; Antenatal corticosteroids; Implementation research; Preterm birth
To determine population-based stillbirth rates and to determine whether the timing and maturity of the stillbirths suggest a high proportion of potentially preventable deaths.
Prospective observational study.
Communities in six low-income countries (Democratic Republic of Congo, Kenya, Zambia, Guatemala, India, and Pakistan) and one site in a mid-income country (Argentina).
Pregnant women residing in the study communities.
Over a five-year period, in selected catchment areas, using multiple methodologies, trained study staff obtained pregnancy outcomes on each delivery in their area.
Main outcome measures
Pregnancy outcome, stillbirth characteristics.
Outcomes of 195 400 deliveries were included. Stillbirth rates ranged from 32 per 1 000 in Pakistan to 8 per 1 000 births in Argentina. Three-fourths (76%) of stillbirth off-spring were not macerated, 63% were ≥37 weeks and 48% weighed 2 500g or more. Across all sites, women with no education, of high and low parity, of older age, and without access to antenatal care were at significantly greater risk for stillbirth (p<0.001). Compared to those delivered by a physician, women delivered by nurses and traditional birth attendants had a lower risk of stillbirth.
In these low-middle income countries, most stillbirth offspring were not macerated, were reported as ≥37 weeks’ gestation, and almost half weighed at least 2 500g. With access to better medical care, especially in the intrapartum period, many of these stillbirths could likely be prevented.
Developing countries; intrapartum stillbirth; stillbirth
Nearly half the world’s babies are born at home. We sought to evaluate the training, knowledge, skills, and access to medical equipment and testing for home birth attendants across 7 international sites.
Face-to-face interviews were done by trained interviewers to assess level of training, knowledge and practices regarding care during the antenatal, intrapartum and postpartum periods. The survey was administered to a sample of birth attendants conducting home or out-of-facility deliveries in 7 sites in 6 countries (India, Pakistan, Guatemala, Democratic Republic of the Congo, Kenya and Zambia).
A total of 1226 home birth attendants were surveyed. Less than half the birth attendants were literate. Eighty percent had one month or less of formal training. Most home birth attendants did not have basic equipment (e.g., blood pressure apparatus, stethoscope, infant bag and mask manual resuscitator). Reporting of births and maternal and neonatal deaths to government agencies was low. Indian auxilliary nurse midwives, who perform some home but mainly clinic births, were far better trained and differed in many characteristics from the birth attendants who only performed deliveries at home.
Home birth attendants in low-income countries were often illiterate, could not read numbers and had little formal training. Most had few of the skills or access to tests, medications and equipment that are necessary to reduce maternal, fetal or neonatal mortality.
Home births; Traditional birth attendants; Perinatal mortality
To identify serum markers of subsequent spontaneous preterm birth (SPTB) in asymptomatic women prior to labor.
Serum proteomics was applied to sera from 80 pregnant women sampled at 24 weeks and an additional 80 pregnant women sampled at 28 weeks. Half had uncomplicated pregnancies and half SPTB.
Three specific peptides arising from inter-alpha-trypsin inhibitor heavy chain 4 protein were significantly reduced in women at 24 and 28 weeks having subsequent SPTB. The most discriminating peptide had a sensitivity of 65.0% and specificity of 82.5%, OR=8.8, CI: 3.1-24.8. A combination of the 3 new biomarkers and 6 previously studied biomarkers increased sensitivity to 86.5% with a specificity of 80.6% at 28 weeks.
Three novel serum markers of SPTB have been identified using serum proteomics. Using a combination of these new markers with additional markers, women at risk of SPTB can be identified weeks prior to SPTB.
Proteomics; Mass Spectrometry; Preterm Birth; Biomarker; Amino Acid Sequencing
We examined individual, household, and neighborhood correlates of intimate partner violence (IPV) before and during pregnancy.
We used multilevel modeling to investigate IPV among 2887 pregnant women in 112 census tracts who sought prenatal care in 8 public clinics in Jefferson County, Alabama, from 1997 through 2001. Data were collected from the Perinatal Emphasis Research Center project, the 2000 Census, and the local Sheriff and Police Departments Uniform Crime Reports for 1997 through 2001.
Participants were predominantly young, African American, on Medicaid, and residents of low-income neighborhoods. The prevalence of past-year male partner–perpetrated physical or sexual violence was 7.4%. Neighborhood residential stability, women performing most of the housework (lack of involvement among partners), being unmarried (being in an uncommitted relationship), and alcohol use were positively associated with elevated IPV risk. Significant protective factors for IPV included older age at first vaginal intercourse and a greater sense of mastery (e.g., the perception of oneself as an effective person).
Both neighborhood contextual and individual and household compositional effects are associated with IPV among low-income pregnant women. The results imply that combined interventions to improve neighborhood conditions and strengthen families may effectively reduce IPV.
We determined the prevalence of first lifetime use of cigarettes during pregnancy or in the early postpartum period (incident smoking) and identified sociodemographic and health-related characteristics of incident smokers.
We used statistics based on data from a longitudinal study of a large cohort of pregnant, low-income, urban women (n=1,676) to describe the timing of first-time use and to compare incident smokers with those who had never smoked and those who had already smoked prior to pregnancy.
About one in 10 (10.2%) women who had not previously smoked initiated cigarette smoking during pregnancy or in the early postpartum period. Compared with those who had never smoked, incident smokers were more likely to report high levels of stress and to have elevated levels of depressive symptomatology, which may be rooted in relatively poor social and economic conditions.
A significant number of women may be initiating smoking during pregnancy or in the early postpartum period. These women have characteristics that are consistent with the risk factors associated with smoking. Further research is warranted to determine prevalence in other populations, identify the risk factors for incident smoking, and assess the potential for primary prevention efforts designed to help women who had previously avoided cigarette use to remain smoke-free throughout pregnancy and in the postpartum period.
To compare the accuracy of the reported date of the last menstrual period (LMP) with that of symphysis-fundal height (SFH) in the estimation of gestational age (GA), using an ultrasound (US) scan as reference.
Gestational age was concurrently assessed by the 3 methods in this prospective, population-based, pregnancy-outcome study conducted in Hyderabad, Pakistan, from June 18, 2003, through August 31, 2005, with 1128 women between 20 and 26 weeks of a singleton pregnancy.
The mean GA was less by ultrasound than by SFH measurement or the reported LMP, and the mean differences with the US result were statistically significant (P <0.001 for both). At delivery, about 75% of the GA values estimated by SFH measurement were within 7 days and almost 91% were within 14 days of the estimation by ultrasound, compared with 65% and 82% for the GA estimated by the reported LMP. Moreover, using the US as reference, the SFH correctly classified 84% of the term, 68% of the preterm, and 86% of the post-term deliveries (weighted κ = 0.58) compared with the corresponding 79%, 61%, and 55% predicted by the reported LMP (weighted κ = 0.44).
The SFH measurement was found to be more accurate than the reported LMP as a tool to estimate GA and therefore date of delivery, but neither were as accurate as a US scan.
Gestational age; Last menstrual period; Pakistan; Symphysis-fundal height; Ultrasound
Because of a physician shortage in many low-income countries, the use of nonphysicians to classify perinatal mortality (stillbirth and early neonatal death) using verbal autopsy could be useful.
To determine the extent to which underlying perinatal causes of deaths assigned by nonphysicians in Guatemala, Pakistan, Zambia, and the Democratic Republic of the Congo using a verbal autopsy method are concordant with underlying perinatal cause of death assigned by physician panels.
Using a train-the-trainer model, 13 physicians and 40 nonphysicians were trained to determine cause of death using a standardized verbal autopsy training program. Subsequently, panels of two physicians and individual nonphysicians from this trained cohort independently reviewed verbal autopsy data from a sample of 118 early neonatal deaths and 134 stillbirths. With the cause of death assigned by the physician panel as the reference standard, sensitivity, specificity, positive and negative predictive values, and cause-specific mortality fractions were calculated to assess nonphysicians' coding responses. Robustness criteria to assess how well nonphysicians performed were used.
Causes of early neonatal death and stillbirth assigned by nonphysicians were concordant with physician-assigned causes 47% and 57% of the time, respectively. Tetanus filled robustness criteria for early neonatal death, and cord prolapse filled robustness criteria for stillbirth.
There are significant differences in underlying cause of death as determined by physicians and nonphysicians even when they receive similar training in cause of death determination. Currently, it does not appear that nonphysicians can be used reliably to assign underlying cause of perinatal death using verbal autopsy.
To determine whether treatment of trichomoniasis increases the risk of prematurity.
Sub-analysis of a randomised trial.
We analysed data from HPTN 024, a randomised trial of antenatal and intrapartum antibiotics to reduce chorioamnionitis-related perinatal HIV transmission.
Pregnant women from four sites in Africa.
Gestational age at the time of delivery or mean birth weight.
Of 2 428 women-infant pairs included, 428 (18%) had trichomoniasis at enrolment. There were no differences in infant age or birth weight between women with or without trichomoniasis. By randomisation group, there were no differences in gestational age at birth or birth weight. Of the 428 women diagnosed with trichomoniasis, 365 (83%) received antibiotics and 63 (15%) did not. In analysis of actual use of antibiotics, women with trichomoniasis who received no treatment were more likely to deliver a preterm infant when the symphysis-fundal height was used to estimate gestational age (36% v. 23%; p=0.03), but not when the Ballard score was used (16% v. 21%; p=0.41). There were no differences in mean birth weight between groups.
In pregnant women in sub-Saharan Africa, most of whom were HIV-infected, neither trichomoniasis nor its treatment appears to influence the risk of preterm birth or a low-birth-weight infant.
Assess population attributable fractions (PAFs) for late postnatal transmission (LPT) of human immunodeficiency virus-1 (HIV-1) in a cohort of HIV-1-exposed infants.
We used data established from a risk factor analysis of LPT (negative HIV-1 results through the 4-6 week visit, but positive assays thereafter through the 12-month visit) from a perinatal clinical trial conducted in three sub-Saharan countries. PAFs were calculated as the proportions of excess LPTs attributed to identified risk factors.
For the cohort of 1317 infants, 206 (15.6%) had only low maternal CD4+ counts (< 200 cells/mm3), 332 (25.2%) had only high maternal plasma viral loads (VLs) (> 50 000 copies/mL), and 81 (6.2%) had both low CD4+ counts and high VLs. Their PAFs were 26.0% [95% confidence interval (CI), 12.0%-36.0%], 37.0% (95% CI, 22.0%-51.0%) and 16.0% (95% CI, 6.0%-25.0%), respectively.
Our PAF analysis illustrates the public health impact of the substantial proportion of LPTs accounted for by high-risk women with both low CD4+ counts and high VLs. In light of these results, access to and use of antiretroviral therapy (ART) by high-risk HIV-1-infected pregnant women is essential. Additional strategies to reduce LPT for those not meeting criteria for ART should be implemented.
Breast feeding; late postnatal transmission; prevention of mother to child transmission/vertical transmission; risk factors; viral load
Infection is a well acknowledged cause of stillbirths and may account for about half of all perinatal deaths today, especially in developing countries. This review presents the impact of interventions targeting various important infections during pregnancy on stillbirth or perinatal mortality.
We undertook a systematic review including all relevant literature on interventions dealing with infections during pregnancy for assessment of effects on stillbirths or perinatal mortality. The quality of the evidence was assessed using the adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach by Child Health Epidemiology Reference Group (CHERG). For the outcome of interest, namely stillbirth, we applied the rules developed by CHERG to recommend a final estimate for reduction in stillbirth for input to the Lives Saved Tool (LiST) model.
A total of 25 studies were included in the review. A random-effects meta-analysis of observational studies of detection and treatment of syphilis during pregnancy showed a significant 80% reduction in stillbirths [Relative risk (RR) = 0.20; 95% confidence interval (CI): 0.12 - 0.34) that is recommended for inclusion in the LiST model. Our meta-analysis showed the malaria prevention interventions i.e. intermittent preventive treatment (IPTp) and insecticide-treated mosquito nets (ITNs) can reduce stillbirths by 22%, however results were not statistically significant (RR = 0.78; 95% CI: 0.59 – 1.03). For human immunodeficiency virus infection, a pooled analysis of 6 radomized controlled trials (RCTs) failed to show a statistically significant reduction in stillbirth with the use of antiretroviral in pregnancy compared to placebo (RR = 0.93; 95% CI: 0.45 – 1.92). Similarly, pooled analysis combining four studies for the treatment of bacterial vaginosis (3 for oral and 1 for vaginal antibiotic) failed to yield a significant impact on perinatal mortality (OR = 0.88; 95% CI: 0.50 – 1.55).
The clearest evidence of impact in stillbirth reduction was found for adequate prevention and treatment of syphilis infection and possibly malaria. At present, large gaps exist in the growing list of stillbirth risk factors, especially those that are infection related. Potential causes of stillbirths including HIV and TORCH infections need to be investigated further to help establish the role of prevention/treatment and its subsequent impact on stillbirth reduction.
Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated.
A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women's and Children's Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC) and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months); neurocognitive development (12 and 18 months); and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial.
Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will provide a strong rationale for global efforts to enhance local supplies of meat as a complementary food for young children.
Maternal and newborn mortality rates remain unacceptably high, especially where the majority of births occur in home settings or in facilities with inadequate resources. The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes. However, the effectiveness of emergency obstetric and neonatal care services has never been proven. Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes.
We have developed a cluster-randomized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization, birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities. This trial will take place in 106 clusters (300-500 deliveries per year each) across 7 sites of the Global Network for Women's and Children's Health Research in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. The trial intervention has three key elements, community mobilization, home-based life saving skills for communities and birth attendants, and training of providers at obstetric facilities to improve quality of care. The primary outcome of the trial is perinatal mortality. Secondary outcomes include rates of stillbirth, 7-day neonatal mortality, maternal death or severe morbidity (including obstetric fistula, eclampsia and obstetrical sepsis) and 28-day neonatal mortality.
In this trial, we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes. If successful, the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries.
We assessed the effect of prenatal and peripartum antibiotics on maternal morbidity and mortality among HIV-infected and uninfected women.
A multicenter trial was conducted at clinical sites in 4 Sub-Saharan African cities: Blantyre and Lilongwe, Malawi; Dar es Salaam, Tanzania; and Lusaka, Zambia. A total of 1558 HIV-infected and 271 uninfected pregnant women who were eligible to receive both the prenatal and peripartum antibiotic/placebo regimens were enrolled. Pregnant women were interviewed at 20–24 weeks of gestation and a physical examination was performed. Women were randomized to receive either antibiotics or placebo. At the 26–30 week visit, participants were given antibiotics or placebo to be taken every 4 hours beginning at the onset of labor and continuing after delivery 3 times a day until a 1-week course was completed. Logistic regression and Cox proportional hazards models were used.
There were no significant differences between the antibiotic and placebo groups for medical conditions, obstetric complications, physical examination findings, puerperal sepsis, and death in either the HIV-infected or the uninfected cohort.
Administration of study antibiotics during pregnancy had no effect on maternal morbidity and mortality among HIV-infected and uninfected pregnant women.
Antibiotics; HIV; Maternal morbidity; Maternal mortality; Pregnancy