The Effect of Intermittent Antenatal Iron Supplementation on Maternal and Infant Outcomes in Rural Viet Nam: A Cluster Randomised Trial

Background

Anemia affects over 500 million women, and in pregnancy is associated with impaired maternal and infant outcomes. Intermittent antenatal iron supplementation is an attractive alternative to daily dosing; however, the impact of this strategy on infant outcomes remains unclear. We compared the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Viet Nam.

Methods and Findings

This cluster randomised trial was conducted in Ha Nam province, Viet Nam. 1,258 pregnant women (<16 wk gestation) in 104 communes were assigned to daily iron–folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Mean birth weight was 3,148 g (standard deviation 416). There was no difference in the birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference [MD] 28 g; 95% CI −22 to 78), or twice weekly MMN compared to daily IFA (MD −36.8 g; 95% CI −82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (geometric mean ratio 0.62; 95% CI 0.57 to 0.68), but there was no difference in hemoglobin levels. Infants of mothers who received twice weekly IFA had higher cognitive scores at 6 mo of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56).

Conclusions

Twice weekly antenatal IFA or MMN did not produce a clinically important difference in birth weight, when compared to daily IFA supplementation. The significant improvement in infant cognitive outcomes at 6 mo of age following twice weekly antenatal IFA requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal IFA in populations with low rates of iron deficiency.

Trial registration

Australia New Zealand Clinical Trials Registry 12610000944033 Please see later in the article for the Editors'' Summary     

Evaluation of a Cluster-Randomized Controlled Trial of a Package of Community-Based Maternal and Newborn Interventions in Mirzapur,Bangladesh

Background

To evaluate a delivery strategy for newborn interventions in rural Bangladesh.

Methods

A cluster-randomized controlled trial was conducted in Mirzapur, Bangladesh. Twelve unions were randomized to intervention or comparison arm. All women of reproductive age were eligible to participate. In the intervention arm, community health workers identified pregnant women; made two antenatal home visits to promote birth and newborn care preparedness; made four postnatal home visits to negotiate preventive care practices and to assess newborns for illness; and referred sick neonates to a hospital and facilitated compliance. Primary outcome measures were antenatal and immediate newborn care behaviours, knowledge of danger signs, care seeking for neonatal complications, and neonatal mortality.

Findings

A total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm, respectively. High coverage of antenatal (91% visited twice) and postnatal (69% visited on days 0 or 1) home visitations was achieved. Indicators of care practices and knowledge of maternal and neonatal danger signs improved. Adjusted mortality hazard ratio in the intervention arm, compared to the comparison arm, was 1.02 (95% CI: 0.80–1.30) at baseline and 0.87 (95% CI: 0.68–1.12) at endline. Primary causes of death were birth asphyxia (49%) and prematurity (26%). No adverse events associated with interventions were reported.

Conclusion

Lack of evidence for mortality impact despite high program coverage and quality assurance of implementation, and improvements in targeted newborn care practices suggests the intervention did not adequately address risk factors for mortality. The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions. Programs must ensure skilled care during childbirth, including management of birth asphyxia and prematurity, and curative postnatal care during the first two days of life, in addition to essential newborn care and infection prevention and management.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00198627","term_id":"NCT00198627"}}NCT00198627     

Influenza-related mortality trends in Japanese and American seniors: evidence for the indirect mortality benefits of vaccinating schoolchildren

Background

The historical Japanese influenza vaccination program targeted at schoolchildren provides a unique opportunity to evaluate the indirect benefits of vaccinating high-transmitter groups to mitigate disease burden among seniors. Here we characterize the indirect mortality benefits of vaccinating schoolchildren based on data from Japan and the US.

Methods

We compared age-specific influenza-related excess mortality rates in Japanese seniors aged ≥65 years during the schoolchildren vaccination program (1978–1994) and after the program was discontinued (1995–2006). Indirect vaccine benefits were adjusted for demographic changes, socioeconomics and dominant influenza subtype; US mortality data were used as a control.

Results

We estimate that the schoolchildren vaccination program conferred a 36% adjusted mortality reduction among Japanese seniors (95%CI: 17–51%), corresponding to ∼1,000 senior deaths averted by vaccination annually (95%CI: 400–1,800). In contrast, influenza-related mortality did not change among US seniors, despite increasing vaccine coverage in this population.

Conclusions

The Japanese schoolchildren vaccination program was associated with substantial indirect mortality benefits in seniors.     

Effectiveness of Influenza Vaccination in Patients with End-Stage Renal Disease Receiving Hemodialysis: A Population-Based Study

Background

Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.

Methods

We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.

Results

The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72–0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75–0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64–1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12–0.33) and mortality (adjusted HR 0.50, 95% CI 0.41–0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26–0.35) after counting vaccination for multi-years.

Conclusions

ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.     

Earlier Initiation and Use of a Greater Number of Iron-Folic Acid Supplements during Pregnancy Prevents Early Neonatal Deaths in Nepal and Pakistan

Introduction

Early neonatal deaths account for 75% of neonatal deaths globally. Antenatal iron-folic acid (IFA) supplementation has significantly reduced the risk of early neonatal deaths in China and Indonesia. We investigated the impact of antenatal IFA supplements on the risk of early neonatal deaths in Nepal and Pakistan during the last decade.

Methods

Data from the most recent singleton live-births of 8,186 from two Nepal Demographic and Health Surveys (DHS) and 13,034 from two Pakistan DHS were selected for the current study. The primary outcome was early neonatal deaths and the main study variable was antenatal IFA supplementation. Analyses used multivariate Cox proportional regression, adjusted for the cluster sampling design and for 18 potential confounders.

Findings

The adjusted risk of early neonatal deaths was significantly reduced by 51% (aHR = 0.49, 95% CI = 0.32–0.75) in Nepal and 23% (aHR = 0.77, 95% CI = 0.59–0.99) in Pakistan with any use of IFA compared to none. When IFA supplementation started at or before the 5^th month of pregnancy, the adjusted risk of early neonatal mortality was significantly reduced by 53% in Nepal, and 28% in Pakistan, compared to no IFA. When >90 IFA supplements were used and started at or before 5^th months, the adjusted risk of early neonatal deaths was significantly reduced by 57% in Nepal, and 45% in Pakistan. In Nepal 4,600 and in Pakistan 75,000 early neonatal deaths could be prevented annually if all pregnant women used >90 IFA supplements and started at or before the 5^th month of pregnancy.

Conclusions

Any use of IFA supplements was significantly associated with reduced risk of early neonatal deaths in Nepal and Pakistan. The greatest mortality sparing effect of IFA on early neonatal deaths in both countries was with early initiation and use of a greater number of supplements.     

Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis

Background

Folic acid is widely used to lower homocysteine concentrations and prevent adverse cardiovascular outcomes. However, the effect of folic acid on cardiovascular events is not clear at the present time. We carried out a comprehensive systematic review and meta-analysis to assess the effects of folic acid supplementation on cardiovascular outcomes.

Methodology and Principal Findings

We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. We included randomized placebo-controlled trials that reported on the effects of folic acid on cardiovascular events compared to placebo. Of 1594 identified studies, we included 16 trials reporting data on 44841 patients. These studies reported 8238 major cardiovascular events, 2001 strokes, 2917 myocardial infarctions, and 6314 deaths. Folic acid supplementation as compared to placebo had no effect on major cardiovascular events (RR, 0.98; 95% CI, 0.93–1.04), stroke (RR, 0.89; 95% CI,0.78–1.01), myocardial infarction (RR, 1.00; 95% CI, 0.93–1.07), or deaths from any cause (RR, 1.00;95% CI, 0.96–1.05). Moreover, folic acid as compared to placebo also had no effect on the following secondary outcomes: risk of revascularization (RR, 1.05; 95%CI, 0.95–1.16), acute coronary syndrome (RR, 1.06; 95%CI, 0.97–1.15), cancer (RR, 1.08; 95%CI, 0.98–1.21), vascular death (RR, 0.94; 95%CI,0.88–1.02), or non-vascular death (RR, 1.06; 95%CI, 0.97–1.15).

Conclusion/Significance

Folic acid supplementation does not effect on the incidence of major cardiovascular events, stroke, myocardial infarction or all cause mortality.     

Maternal and Perinatal Outcomes of Twin Pregnancy in 23 Low- and Middle-Income Countries

Background

Twin pregnancies in low- and middle-income countries (LMICs) pose a high risk to mothers and newborns due to inherent biological risks and scarcity of health resources. We conducted a secondary analysis of the WHO Global Survey dataset to analyze maternal and perinatal outcomes in twin pregnancies and factors associated with perinatal morbidity and mortality in twins.

Methods

We examined maternal and neonatal characteristics in twin deliveries in 23 LMICs and conducted multi-level logistic regression to determine the association between twins and adverse maternal and perinatal outcomes.

Results

279,425 mothers gave birth to 276,187 (98.8%) singletons and 6,476 (1.2%) twins. Odds of severe adverse maternal outcomes (death, blood transfusion, ICU admission or hysterectomy) (AOR 1.85, 95% CI 1.60–2.14) and perinatal mortality (AOR 2.46, 95% CI 1.40–4.35) in twin pregnancies were higher, however early neonatal death (AOR 2.50, 95% CI 0.95–6.62) and stillbirth (AOR 1.22, 95% CI 0.58–2.57) did not reach significance. Amongst twins alone, maternal age <18, poor education and antenatal care, nulliparity, vaginal bleeding, non-cephalic presentations, birth weight discordance >15%, born second, preterm birth and low birthweight were associated with perinatal mortality. Marriage and caesarean section were protective.

Conclusions

Twin pregnancy is a significant risk factor for maternal and perinatal morbidity and mortality in low-resource settings; maternal risk and access to safe caesarean section may determine safest mode of delivery in LMICs. Improving obstetric care in twin pregnancies, particularly timely access to safe caesarean section, is required to reduce risk to mother and baby.     

Determinants and Causes of Neonatal Mortality in Jimma Zone,Southwest Ethiopia: A Multilevel Analysis of Prospective Follow Up Study

Background

Ethiopia is among the countries with the highest neonatal mortality with the rate of 37 deaths per 1000 live births. In spite of many efforts by the government and other partners, non-significant decline has been achieved in the last 15 years. Thus, identifying the determinants and causes are very crucial for policy and program improvement. However, studies are scarce in the country in general and in Jimma zone in particular.

Objective

To identify the determinants and causes of neonatal mortality in Jimma Zone, Southwest Ethiopia.

Methods

A prospective follow-up study was conducted among 3463 neonates from September 2012 to December 2013. The data were collected by interviewer-administered structured questionnaire and analyzed by SPSS V.20.0 and STATA 13. Verbal autopsies were conducted to identify causes of neonatal death. Mixed-effects multilevel logistic regression model was used to identify determinants of neonatal mortality.

Results

The status of neonatal mortality rate was 35.5 (95%CI: 28.3, 42.6) per 1000 live births. Though significant variation existed between clusters in relation to neonatal mortality, cluster-level variables were found to have non-significant effect on neonatal mortality. Individual-level variables such as birth order, frequency of antenatal care use, delivery place, gestation age at birth, premature rupture of membrane, complication during labor, twin births, size of neonate at birth and neonatal care practice were identified as determinants of neonatal mortality. Birth asphyxia (47.5%), neonatal infections (34.3%) and prematurity (11.1%) were the three leading causes of neonatal mortality accounting for 93%.

Conclusions

This study revealed high status of neonatal mortality in the study area. Higher-level variables had less importance in determining neonatal mortality. Individual level variables related to care during pregnancy, intra-partum complications and care, neonatal conditions and the immediate neonatal care practices were identified as determinant factors. Improving antenatal care, intra-partum care and immediate neonatal care are recommended.     

Vaccinating Sons against HPV: Results from a U.S. National Survey of Parents

Purpose

The quadrivalent HPV vaccination was approved for use in males ages 9 to 26 in 2009 and recommended for routine administration in 2011. The purpose of this study was to uncover predictable commonalities amongst parents who chose to vaccinate their 11–17 year old sons against HPV.

Methods

We compiled data from a U.S. national sample of 779 parents with sons 11–17 years old using a web-based survey to gather information about behavioral and sociodemographic factors which predicted receipt of 1 or more HPV vaccine doses based on parental report. Predictors were first modeled individually for univariable associations. Significant predictors (p<0.10) were combined in a multivariable model.

Results

In the adjusted model, independent predictors included receipt of flu vaccination, health insurance coverage and sexual health topic discussions with sons. Sons who had received a flu shot in the last two years more frequently received at least one dose of the vaccine (OR 1.82; 95% CI 1.45–2.26). Sons covered by private health insurance had decreased odds of HPV vaccination (OR 0.56 95% CI 0.37–0.83). Lastly, parents who had discussed sexual health topics with their sons were more likely to vaccinate (OR 1.61; 95% CI 1.37–1.89).

Conclusions

Male vaccination rates in the U.S. have increased, but males continue to be under-immunized. Utilization of health care is an important factor in HPV vaccine uptake; therefore, health care providers should use every contact as an opportunity to vaccinate. Communication about sexual health topics may provide a forum for parents and health care providers to have conversations about HPV vaccination as those more comfortable discussing these topics may also be more comfortable discussing HPV vaccination.     

Maternal and Neonatal Mortality in South-West Ethiopia: Estimates and Socio-Economic Inequality

Introduction

Ethiopia has achieved the fourth Millennium Development Goal by reducing under 5 mortality. Nevertheless, there are challenges in reducing maternal and neonatal mortality. The aim of this study was to estimate maternal and neonatal mortality and the socio-economic inequalities of these mortalities in rural south-west Ethiopia.

Methods

We visited and enumerated all households but collected data from those that reported pregnancy and birth outcomes in the last five years in 15 of the 30 rural kebeles in Bonke woreda, Gamo Gofa, south-west Ethiopia. The primary outcomes were maternal and neonatal mortality and a secondary outcome was the rate of institutional delivery.

Results

We found 11,762 births in 6572 households; 11,536 live and 226 stillbirths. There were 49 maternal deaths; yielding a maternal mortality ratio of 425 per 100,000 live births (95% CI:318–556). The poorest households had greater MMR compared to richest (550 vs 239 per 100,000 live births). However, the socio-economic factors examined did not have statistically significant association with maternal mortality. There were 308 neonatal deaths; resulting in a neonatal mortality ratio of 27 per 1000 live births (95% CI: 24–30). Neonatal mortality was greater in households in the poorest quartile compared to the richest; adjusted OR (AOR): 2.62 (95% CI: 1.65–4.15), headed by illiterates compared to better educated; AOR: 3.54 (95% CI: 1.11–11.30), far from road (≥6 km) compared to within 5 km; AOR: 2.40 (95% CI: 1.56–3.69), that had three or more births in five years compared to two or less; AOR: 3.22 (95% CI: 2.45–4.22). Households with maternal mortality had an increased risk of stillbirths; OR: 11.6 (95% CI: 6.00–22.7), and neonatal deaths; OR: 7.2 (95% CI: 3.6–14.3). Institutional delivery was only 3.7%.

Conclusion

High mortality with socio-economic inequality and low institutional delivery highlight the importance of strengthening obstetric interventions in rural south-west Ethiopia.     

Diphtheria in Lao PDR: Insufficient Coverage or Ineffective Vaccine?

Background

During late 2012 and early 2013 several outbreaks of diphthe-ria were notified in the North of the Lao People’s Democratic Republic. The aim of this study was to determine whether the re-emergence of this vaccine-preventable disease was due to insufficient vaccination coverage or reduction of vaccine effectiveness within the affected regions.

Methods

A serosurvey was conducted in the Huaphan Province on a cluster sampling of 132 children aged 12–59 months. Serum samples, socio-demographic data, nutri-tional status and vaccination history were collected when available. Anti-diphtheria and anti-tetanus IgG antibody levels were measured by ELISA.

Results

Overall, 63.6% of participants had detectable diphtheria antibodies and 71.2% tetanus antibodies. Factors independently associated with non-vaccination against diphtheria were the distance from the health centre (OR: 6.35 [95% CI: 1.4–28.8], p = 0.01), the Lao Theung ethnicity (OR: 12.2 [95% CI:1,74–85, 4], p = 0.01) and the lack of advice on vac-cination given at birth (OR: 9.8 [95% CI: 1.5–63.8], (p = 0.01) while the level of maternal edu-cation was a protective factor (OR: 0.08 [95% CI: 0.008–0.81], p = 0.03). Most respondents claimed financial difficulties as the main reason for non-vaccination. Out of 55 children whose vaccination certificates stated that they were given all 3 doses of diphtheria-containing vaccine, 83.6% had diphtheria antibodies and 92.7% had tetanus antibodies. Furthermore, despite a high prevalence of stunted and underweight children (53% and 25.8%, respectively), the low levels of anti-diphtheria antibodies were not correlated to the nutritional status.

Conclusions

Our data highlight a significant deficit in both the vaccination coverage and diphtheria vaccine effectiveness within the Huaphan Province. Technical defi-ciencies in the methods of storage and distribution of vaccines as well as unreliability of vac-cination cards are discussed. Several hypotheses are advanced to explain such a decline in immunity against diphtheria and recommendations are provided to prevent future outbreaks.     

Effectiveness of Antenatal Clinics to Deliver Intermittent Preventive Treatment and Insecticide Treated Nets for the Control of Malaria in Pregnancy in Kenya

Background

Malaria in pregnancy can have devastating consequences for mother and baby. Coverage with the WHO prevention strategy for sub-Saharan Africa of intermittent-preventive-treatment (IPTp) with two doses of sulphadoxine-pyrimethamine (SP) and insecticide-treated-nets (ITNs) in pregnancy is low. We analysed household survey data to evaluate the effectiveness of antenatal clinics (ANC) to deliver IPTp and ITNs to pregnant women in Nyando district, Kenya.

Methods

We assessed the systems effectiveness of ANC to deliver IPTp and ITNs to pregnant women and the impact on low birthweight (LBW). Logistic regression was used to identify predictors of receipt of IPTp and ITN use during pregnancy.

Results

Among 89% of recently pregnant women who attended ANC at least once between 4–9 months gestation, 59% reported receiving one dose of SP and 90% attended ANC again, of whom 57% received a second dose, resulting in a cumulative effectiveness for IPTp of 27%, most of whom used an ITN (96%). Overall ITN use was 89%, and ANC the main source (76%). Women were less likely to receive IPTp if they had low malaria knowledge (0.26, 95% CI 0.08–0.83), had a child who had died (OR 0.36, 95% CI 0.14–0.95), or if they first attended ANC late (OR 0.20, 95% CI 0.06–0.67). Women who experienced side effects to SP (OR 0.18, CI 0.03–0.90) or had low malaria knowledge (OR 0.78, 95% CI 0.11–5.43) were less likely to receive IPTp by directly observed therapy. Ineffective delivery of IPTp reduced its potential impact by 231 LBW cases averted (95% CI 64–359) per 10,000 pregnant women.

Conclusion

IPTp presents greater challenges to deliver through ANC than ITNs in this setting. The reduction in public health impact on LBW resulting from ineffective delivery of IPTp is estimated to be substantial. Urgent efforts are required to improve service delivery of this important intervention.     

Adequately Diversified Dietary Intake and Iron and Folic Acid Supplementation during Pregnancy Is Associated with Reduced Occurrence of Symptoms Suggestive of Pre-Eclampsia or Eclampsia in Indian Women

Background/Objective

Pre-eclampsia or Eclampsia (PE or E) accounts for 25% of cases of maternal mortality worldwide. There is some evidence of a link to dietary factors, but few studies have explored this association in developing countries, where the majority of the burden falls. We examined the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E in Indian women.

Methods

Cross-sectional data from India’s third National Family Health Survey (NFHS-3, 2005-06) was used for this study. Self-reported symptoms suggestive of PE or E during pregnancy were obtained from 39,657 women aged 15-49 years who had had a live birth in the five years preceding the survey. Multivariable logistic regression analysis was used to estimate the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E after adjusting for maternal, health and lifestyle factors, and socio-demographic characteristics of the mother.

Results

In their most recent pregnancy, 1.2% (n=456) of the study sample experienced symptoms suggestive of PE or E. Mothers who consumed an adequately diversified diet were 34% less likely (OR: 0.66; 95% CI: 0.51-0.87) to report PE or E symptoms than mothers with inadequately diversified dietary intake. The likelihood of reporting PE or E symptoms was also 36% lower (OR: 0.64; 95% CI: 0.47-0.88) among those mothers who consumed iron and folic acid supplementation for at least 90 days during their last pregnancy. As a sensitivity analysis, we stratified our models sequentially by education, wealth, antenatal care visits, birth interval, and parity. Our results remained largely unchanged: both adequately diversified dietary intake and iron and folic acid supplementation during pregnancy were associated with a reduced occurrence of PE or E symptoms.

Conclusion

Having a adequately diversified dietary intake and iron and folic acid supplementation in pregnancy was associated with a reduced occurrence of symptoms suggestive of PE or E in Indian women.     

Association of Antenatal Depression with Adverse Consequences for the Mother and Newborn in Rural Ghana: Findings from the DON Population-Based Cohort Study

Background

Whilst there is compelling evidence of an almost 2-fold increased risk of still births, and suggestive evidence of increased mortality among offspring of mothers with psychotic disorders, only three studies have addressed the role of antenatal depression (AND) on survival of the baby. We examined these associations in a large cohort of pregnant women in Ghana.

Methods

A Cohort study nested within 4-weekly surveillance of all women of reproductive age to identify pregnancies and collect data on births and deaths in the Kintampo Health Research Centre study area of Ghana. Women were screened for AND using the Patient Health Questionnaire (PHQ-9) to ascertain DSM-IV major or minor depression. Outcomes were adverse birth outcomes, maternal/infant morbidity, and uptake of key newborn care practices, examined using logistic regression; effect sizes reported as relative risks with 95% confidence intervals.

Results

20679 (89.6%) pregnant women completed the PHQ-9. The prevalence of AND was 9.9% (n = 2032) (95% confidence interval 9.4%–10.2%). AND was associated with: prolonged labour (RR 1.25, 95% CI 1.02–1.53); peripartum complications (RR 1.11, 95% CI 1.07–1.15);postpartum complications (RR 1.27, 96% CI 1.21–1.34); non-vaginal delivery (RR 1.19, 95% CI 1.02–1.40); newborn illness (RR 1.52, 95% CI 1.16–1.99); and bed net use during pregnancy (RR 0.93, 95% CI 0.89–0.98), but not neonatal deaths, still births, low birth weight, immediate breast feeding initiation, or exclusive breastfeeding. AND was marginally associated with preterm births (RR 1.32, 95% CI 0.98–1.76).

Conclusion

This paper has contributed important evidence on the role of antenatal depression as a potential contributor to maternal and infant morbidity. Non-pharmacological treatments anchored on primary care delivery structures are recommended as an immediate step. We further recommend that trials are designed to assess if treating antenatal depression in conjunction with improving the quality of obstetric care results in improved maternal and newborn outcomes.     

The Effects of Periconceptional Risk Factor Exposure and Micronutrient Supplementation on Birth Defects in Shaanxi Province in Western China

Objectives

1) To understand the current prevalence and main types of birth defects, 2) assess the periconceptional exposure of factors associated with birth defects in Shaanxi Province, and 3) provide scientific evidence for local governments to formulate services for the primary prevention of birth defects.

Methods

We sampled 16,541 households from 128 townships in 16 counties/districts in Shaanxi province using a multi-stage random sampling method. Among them, 10,544 women who had live born or stillborn infants with gestational age ≥28 weeks between 2008 and 2009 were interviewed using a structured questionnaire designed to collect information about periconceptional risk factor exposure, health care service utilization, and micronutrient supplements. Logistic regression was performed to assess the risk factors associated with birth defects and adjustments were made for imbalanced social-demographic characteristics between case and control groups.

Results

The prevalence of congenital birth defect in Shaanxi province was 14.3/1000 births. The environment risk factors associated with birth defects include unhealthy lifestyle (Alcohol, odds ratio (OR): 3.60, 95% confidence interval (CI) 1.64−7.91; Smoking, OR: 1.32, 95% CI: 0.99−1.75; Drink strong tea, OR: 1.81, 95% CI: 1.27−2.59), exposure to heavy pollution (OR: 1.53, 95% CI: 1.01−2.30), maternal diseases (OR: 1.77, 95% CI: 1.35−2.33), drug use (OR: 2.11, 95% CI: 1.51−2.95), maternal chemical pesticide exposure (OR: 2.30, 95% CI: 1.16−4.57), and adverse pregnancy history (OR: 10.10, 95% CI: 7.55−13.53). Periconceptional folic acid or multiple micronutrients including folic acid supplementation, was associated with a reduced rate of birth defects (OR: 0.54, 95% CI: 0.29−0.998).

Conclusions

Health care service utilization, unhealthy lifestyle factors, and environment risk factors seem to be associated with birth defects in Shaanxi province. Governmental agencies should focus on effective primary preventative methods, such as the delivery of periconceptional health education for minimizing potential risk factor exposures, periconceptional folic acid or micronutrient supplementation, environment monitoring, and assessment of factories with high levels of pollution.     

Measuring the performance of vaccination programs using cross-sectional surveys: a likelihood framework and retrospective analysis

Background

The performance of routine and supplemental immunization activities is usually measured by the administrative method: dividing the number of doses distributed by the size of the target population. This method leads to coverage estimates that are sometimes impossible (e.g., vaccination of 102% of the target population), and are generally inconsistent with the proportion found to be vaccinated in Demographic and Health Surveys (DHS). We describe a method that estimates the fraction of the population accessible to vaccination activities, as well as within-campaign inefficiencies, thus providing a consistent estimate of vaccination coverage.

Methods and Findings

We developed a likelihood framework for estimating the effective coverage of vaccination programs using cross-sectional surveys of vaccine coverage combined with administrative data. We applied our method to measles vaccination in three African countries: Ghana, Madagascar, and Sierra Leone, using data from each country''s most recent DHS survey and administrative coverage data reported to the World Health Organization. We estimate that 93% (95% CI: 91, 94) of the population in Ghana was ever covered by any measles vaccination activity, 77% (95% CI: 78, 81) in Madagascar, and 69% (95% CI: 67, 70) in Sierra Leone. “Within-activity” inefficiencies were estimated to be low in Ghana, and higher in Sierra Leone and Madagascar. Our model successfully fits age-specific vaccination coverage levels seen in DHS data, which differ markedly from those predicted by naïve extrapolation from country-reported and World Health Organization–adjusted vaccination coverage.

Conclusions

Combining administrative data with survey data substantially improves estimates of vaccination coverage. Estimates of the inefficiency of past vaccination activities and the proportion not covered by any activity allow us to more accurately predict the results of future activities and provide insight into the ways in which vaccination programs are failing to meet their goals. Please see later in the article for the Editors'' Summary     

One Dose versus Three Weekly Doses of Benzathine Penicillin G for Patients Co-Infected with HIV and Early Syphilis: A Multicenter,Prospective Observational Study

Background

One dose of benzathine penicillin G (BPG) has been recommended for HIV-infected patients with early syphilis (primary, secondary, and early latent syphilis) in the sexually transmitted diseases treatment guidelines, but clinical data to support such a recommendation are limited.

Methods

We prospectively observed the serological response to 1 or 3 weekly doses of BPG in HIV-infected adults who sought treatment of early syphilis at 8 hospitals around Taiwan. Rapid plasma reagin (RPR) titers were followed every 3–6 months after treatment. The serological response was defined as a 4-fold or greater decline in RPR titers at 12 months of treatment. The missing values were treated by following the last-observed-carried-forward principle. We hypothesized that 1 dose was non-inferior to 3 weekly doses of BPG with the non-inferiority margin for the difference of serological response set to 10%.

Results

Between 2007 and 2012, 573 patients completed at least 12 months of follow-up: 295 (51.5%) receiving 1 dose of BPG (1-dose group) and 278 (48.5%) 3 doses (3-dose group). Overall, 198 patients (67.1%; 95% confidence interval [CI], 61.4–72.5%) in the 1-dose group achieved serological response at 12 months, as did 208 patients (74.8%; 95% CI, 69.3–79.8%) in the 3-dose group (one-sided 95% CI of the difference, 15.1%). In the multivariate analysis, secondary syphilis (adjusted odds ratio [AOR], 1.90; 95% CI 1.17–3.09), RPR titer ≥32 (AOR, 1.93; 95% CI, 1.38–2.69), and 3 doses of BPG (AOR, 1.68; 95% CI, 1.20–2.36) were independently associated with a serological response. The time to the first episode of treatment failure was 1184 (standard deviation [SD], 70.5) and 1436 (SD, 80.0) days for 1- and 3-dose group, respectively.

Conclusions

Single-dose BPG resulted in a higher serological failure rate and shorter time to treatment failure than 3 weekly doses of BPG in the treatment of early syphilis in HIV-infected patients.     

Efficacy of Neonatal HBV Vaccination on Liver Cancer and Other Liver Diseases over 30-Year Follow-up of the Qidong Hepatitis B Intervention Study: A Cluster Randomized Controlled Trial

Background

Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined.

Methods and Findings

The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10–14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996–2000 and 2008–2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%–97%), 70% (95% CI 15%–89%), and 69% (95% CI 34%–85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%–30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%–75%). Receiving a booster at age 10–14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio [HR] = 0.68, 95% CI 0.47–0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up.

Conclusions

Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series. Please see later in the article for the Editors'' Summary     

Coverage and Timing of Children's Vaccination: An Evaluation of the Expanded Programme on Immunisation in The Gambia

Objective

To evaluate the coverage and timeliness of the Expanded Programme on Immunisation (EPI) in The Gambia.

Methods

Vaccination data were obtained between January 2005 and December 2012 from the Farafenni Health and Demographic Surveillance System (FHDSS), the Basse Health and Demographic Surveillance System (BHDSS), the Kiang West Demographic surveillance system (KWDSS), a cluster survey in the more urban Western Health Region (WR) and a cross sectional study in four clinics in the semi-urban Greater Banjul area of WR. Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and to assess timeliness to vaccination.

Findings

BCG vaccine uptake was over 95% in all regions. Coverage of DPT1 ranged from 93.2% in BHDSS to 99.8% in the WR. Coverage decreased with increasing number of DPT doses; DPT3 coverage ranged from 81.7% in BHDSS to 99.0% in WR. Measles vaccination coverage ranged from 83.3% in BHDSS to 97.0% in WR. DPT4 booster coverage was low and ranged from 43.9% in the WR to 82.8% in KWDSS. Across all regions, delaying on previous vaccinations increased the likelihood of being delayed for the subsequent vaccination.

Conclusions

The Gambia health system achieves high vaccine coverage in the first year of life. However, there continues to be a delay to vaccination which may impact on the introduction of new vaccines. Examples of effectively functioning EPI programmes such as The Gambia one may well be important models for other low income countries struggling to achieve high routine vaccination coverage.     

Contextual Risk Factors for Low Birth Weight: A Multilevel Analysis

Background

Low birth weight (LBW) remains to be a leading cause of neonatal death and a major contributor to infant and under-five mortality. Its prevalence has not declined in the last decade in sub-Saharan Africa (SSA) and Asia. Some individual level factors have been identified as risk factors for LBW but knowledge is limited on contextual risk factors for LBW especially in SSA.

Methods

Contextual risk factors for LBW in Ghana were identified by performing multivariable multilevel logistic regression analysis of 6,900 mothers dwelling in 412 communities that participated in the 2003 and 2008 Demographic and Health Surveys in Ghana.

Results

Contextual-level factors were significantly associated with LBW: Being a rural dweller increased the likelihood of having a LBW infant by 43% (OR 1.43; 95% CI 1.01–2.01; P-value <0.05) while living in poverty-concentrated communities increased the risk of having a LBW infant twofold (OR 2.16; 95% CI 1.29–3.61; P-value <0.01). In neighbourhoods with a high coverage of safe water supply the odds of having a LBW infant reduced by 28% (OR 0.74; 95% CI 0.57–0.96; P-value <0.05).

Conclusion

This study showed contextual risk factors to have independent effects on the prevalence of LBW infants. Being a rural dweller, living in a community with a high concentration of poverty and a low coverage of safe water supply were found to increase the prevalence of LBW infants. Implementing appropriate community-based intervention programmes will likely reduce the occurrence of LBW infants.