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
Body mass index is not associated with latency or the occurrence of maternal infectious complications during conservative management of preterm premature rupture of fetal membranes.
Obesity has been associated with chronic inflammation. We hypothesized that body mass index (BMI) may be inversely related to latency and directly related to infectious complications following preterm premature rupture of membranes (pPROM).
This secondary analysis of a randomized trial of antibiotics for pPROM had information available for 562 subjects. We analyzed the association between BMI and latency, the occurrence of chorioamnionitis, endometritis and maternal infectious morbidity, after controlling for gestational age (GA) at rupture and treatment group. Survival analysis, regression and test of proportions were used as appropriate.
When evaluated as a categorical or continuous variable, BMI did not reveal any significant associations. Latency to delivery was affected by GA at rupture of membrane and antibiotic therapy, but not by BMI group.
BMI was not associated with latency or the occurrence of maternal infectious complications during conservative management of PROM before 32 weeks gestation.
BMI; Body mass index; Obesity; Premature rupture of membranes; PROM
Recruitment and retention of patients for randomized control trial (RCT) studies can provide formidable challenges, particularly with minority and underserved populations. Data are reported for the Philadelphia Collaborative Preterm Prevention Project (PCPPP), a large RCT targeting risk factors for repeat preterm births among women who previously delivered premature (< 35 weeks gestation) infants.
Design of the PCPPP incorporated strategies to maximize recruitment and retention. These included an advanced database system tracking follow-up status and assessment completion rates; cultural sensitivity training for staff; communication to the community and eligible women of the benefits of participation; financial incentives; assistance with transportation and supervised childcare services; and reminder calls for convenient, flexibly scheduled appointments. Analyses reported here: 1) compare recruitment projections to actual enrollment 2) explore recruitment bias; 3) validate the randomization process 4) document the extent to which contact was maintained and complete assessments achieved 5) determine if follow-up was conditioned upon socio-economic status, race/ethnicity, or other factors.
Of eligible women approached, 1,126 (77.7%) agreed to participate fully. Of the 324 not agreeing, 118 (36.4%) completed a short survey. Consenting women were disproportionately from minority and low SES backgrounds: 71.5% consenting were African American, versus 38.8% not consenting. Consenting women were also more likely to report homelessness during their lifetime (14.6% vs. 0.87%) and to be unmarried at the time of delivery (81.6% versus 47.9%). First one-month postpartum assessment was completed for 83.5% (n = 472) of the intervention group (n = 565) and 76% (426) of the control group. Higher assessment completion rates were observed for the intervention group throughout the follow-up. Second, third, fourth and fifth postpartum assessments were 67.6% vs. 57.5%, 60.0% vs. 48.9%, 54.2% vs. 46.3% and 47.3% vs. 40.8%, for the intervention and control group women, respectively. There were no differences in follow-up rates according to race/ethnicity, SES or other factors. Greater retention of the intervention group may reflect the highly-valued nature of the medical and behavior services constituting the intervention arms of the Project.
Findings challenge beliefs that low income and minority women are averse to enrolling and continuing in clinical trials or community studies.
Our objectives were to assess clinical signs and diagnoses associated with primary HIV-1 infection among infants.
We analyzed data from a clinical trial (HPTN 024) in sub-Saharan Africa. Study visits were conducted at birth, at 4–6 weeks, and at 3, 6, 9, and 12 months. The study population comprised live born, singleton, first born infants of HIV-1-infected women, with negative HIV-1 RNA assays who were still breastfeeding at 4–6 weeks.
Of 1317 HIV-1-exposed infants, 84 became HIV-1-infected after 4–6 weeks and 1233 remained uninfected. There were 102 primary and 5650 non-primary infection visits. The most common signs were cough and diarrhea, and the most common diagnoses were malaria and pneumonia. Primary infection was associated with significantly increased odds of diarrhea [odds radio (OR)=2.4], pneumonia (OR=3.5), otitis media (OR=3.1), and oral thrush (OR=2.9). For the clinical signs and diagnoses evaluated, sensitivity was low (1ȃ16.7%) and specificity was high (88.2%–99%). Positive predictive values ranged from 0.1–1.4%. Negative predictive values ranged from 28.0–51.1%.
Certain clinical signs and diagnoses, although more common during primary HIV-1 infection, had low sensitivity and high specificity. Efforts to expand access to laboratory assays for the diagnosis of primary HIV-1 infection among infants of HIV-1-infected women should be emphasized.
HIV-1; infant; primary infection
To assess the associations between maternal obesity, uterine contraction frequency, and spontaneous preterm birth in at-risk women.
In a secondary analysis, we analyzed data from 253 at-risk women (prior spontaneous preterm birth, vaginal bleeding) enrolled in a multi-center observational study of home uterine activity monitoring at 11 centers. All women wore a uterine activity monitor twice daily from 22 through 34 weeks of gestation. Mean and maximal contractions/hour at 22-24, 25-26, 27-28, 29-30, 31-32, and at or after 33 weeks of gestation were compared between overweight/obese women (a BMI at 22-24 weeks greater than 25 kg/m2) and normal/underweight women (a BMI of at least 25 kg/m2) at each gestational age interval. Multivariable analysis evaluated the influences of BMI, contractions, fetal fibronectin and transvaginal cervical length on spontaneous preterm birth before 35 weeks.
Obese/overweight women (n=156) were significantly less likely to experience spontaneous preterm birth before 35 weeks (8.3 vs 21.7%, p<0.01). For each gestational age interval before 32 weeks, obese/overweight women had fewer mean contractions/hour (P<0.01 for each) and maximal contractions/hour (p<0.01 for each) than normal/underweight women, although their mean cervical lengths (34.3 vs 33.1 mm, p=0.25), and fetal fibronectin levels (7.1% vs. 7.2% ≥50 ng/mL, p=0.97) were similar at study enrollment. Obese/overweight status was associated with a lower risk of spontaneous preterm birth before 35 weeks after controlling for contraction frequency and other factors evaluated at 22-24 and 31-32 weeks, but not at later time periods.
Obese/overweight women at risk for spontaneous preterm birth exhibit less uterine activity and less frequent spontaneous preterm birth before 35 weeks of gestation than normal/underweight women.
Stillbirth is a major obstetric complication, with 3.2 million stillbirths worldwide and 26,000 stillbirths in the United States every year. The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop from October 22–24, 2007, to review the pathophysiology of conditions underlying stillbirth to define causes of death. The optimal classification system would identify the pathophysiologic entity initiating the chain of events that irreversibly led to death. Because the integrity of the classification is based on available pathologic, clinical, and diagnostic data, experts emphasized that a complete stillbirth workup should be performed. Experts developed evidence-based characteristics of maternal, fetal, and placental conditions to attribute a condition as a cause of stillbirth. These conditions include infection, maternal medical conditions, antiphospholipid syndrome, heritable thrombophilias, red cell alloimmunization, platelet alloimmunization, congenital malformations, chromosomal abnormalities including confined placental mosaicism, fetomaternal hemorrhage, placental and umbilical cord abnormalities including vasa previa and placental abruption, complications of multifetal gestation, and uterine complications. In all cases, owing to lack of sufficient knowledge about disease states and normal development, there will be a degree of uncertainty regarding whether a specific condition was indeed the cause of death.
To determine the optimal time for a second HIV-1 nucleic acid amplification assay to detect late postnatal transmission of HIV-1 (first negative test at 4–8 weeks of age) in resource limited settings.
A longitudinal analysis of data from HPTN 024
Children born to HIV-1 infected mothers enrolled in the HIV Prevention Trial Network trial 024 (HPTN 024) were tested for HIV-1 infection at six intervals within the first year of life. Mothers and infants received nevirapine prophylaxis. We estimated the probability of being alive and having a positive test in each interval after 4–8 weeks and at 30 days post-weaning, conditional on having acquired HIV during the late postnatal period. The interval with the highest probability was taken to be the optimal visit interval.
A total of 1609 infants from HPTN 024 had at least one HIV-1 diagnostic test and were included in the analysis. We found that testing at one month after weaning or 12 months of age (whichever comes first), identified 81% of those infected during the late postnatal period (after 4–8 weeks) through breastfeeding. In total, 93% (95% CI: 89,98) of all infected infants would be detected if tests were performed at these two time points.
In resource-limited settings, HIV-1 PCR testing at 4–8 weeks followed by a second test at one month after weaning or at one year of age (whichever comes first), led to the identification of the vast majority of HIV-1 infected infants.
HIV infant diagnosis; late postnatal transmission; breast feeding
Infants born to women who receive intrapartum antibiotics may have higher rates of infectious morbidity and mortality than unexposed infants.
To determine the association of maternal intrapartum antibiotics and early neonatal morbidity and mortality.
Secondary analysis of data from a multi-site randomized placebo-controlled clinical trial of antibiotics to prevent chorioamnionitis-associated mother-to-child transmission of HIV-1 and preterm birth in sub-Saharan Africa. Early neonatal morbidity and mortality were analyzed. In an intent-to-treat (ITT) analysis, infants born to women randomized to antibiotics or placebo were compared. Additionally, non-ITT analysis was performed because some women received non-study antibiotics for various clinical indications.
Overall, 2659 pregnant women were randomized. Of these, 2466 HIV-1-infected and -uninfected women delivered 2413 live born and 84 stillborn infants. In the ITT analysis, there were no significant associations between exposure to antibiotics and early neonatal outcomes. Non-ITT analyses showed more illness at birth (11.2% vs. 8.6%, p=0.03) and more admissions to the Special Care Baby Unit (12.6% vs. 9.8%, p = 0.04) among infants exposed to maternal intrapartum antibiotics than among unexposed infants. Further analyses revealed greater early neonatal morbidity and mortality among infants of mothers who received non-study antibiotics than of mothers who received study antibiotics.
There is no association between intrapartum exposure to antibiotics and early neonatal morbidity or mortality. The associations observed in non-ITT analyses are most likely the result of women with peripartum illnesses being more likely to receive non-study antibiotics.
Antibiotic resistance; Antibiotics; Neonatal morbidity; Neonatal mortality; Neonatal sepsis
Dried blood spots that had been stored ambiently for 3 to 6 years lost approximately 1 log10 of human immunodeficiency virus type 1 (HIV-1) RNA, but the majority could still be genotyped for resistance. Nevirapine resistance was found in 7/16 (43.5%) HIV-1-positive HIVNET 024 infants at 4 to 6 weeks, but no resistance was found at other time points.