The Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials in Mozambique, Pakistan, and India: an individual participant-level meta-analysis

Pregnancy hypertension is the third leading cause of maternal mortality in Mozambique and contributes significantly to fetal and neonatal mortality. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment. The Mozambique Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 administrative posts (clusters) in Maputo and Gaza Provinces. The CLIP intervention (6 clusters) consisted of community engagement, community health worker-provided mobile health-guided clinical assessment, initial treatment, and referral to facility either urgently (<4hrs) or non-urgently (<24hrs), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of CLIP contacts. 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity. 15,013 women (15,123 pregnancies) were recruited in intervention (N=7930; 2·0% loss to follow-up (LTFU)) and control (N=7190; 2·8% LTFU) clusters. The primary outcome did not differ between intervention and control clusters (adjusted odds ratio (aOR) 1·31, 95% confidence interval (CI) [0·70, 2·48]; p=0·40). Compared with intervention arm women without CLIP contacts, those with ≥8 contacts experienced fewer primary outcomes (aOR 0·79 (95% CI 0·63, 0·99); p=0·041), primarily due to improved maternal outcomes (aOR 0·72 (95% CI 0·53, 0·97); p=0·033). As generally implemented, the CLIP intervention did not improve pregnancy outcomes; community implementation of the WHO eight contact model may be beneficial. The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337).

Pregnancy hypertension is associated with 7.1% of maternal deaths in India. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment. The Indian Community-Level Interventions for Pre-eclampsia (CLIP) open-label cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 clusters (initial four-cluster internal pilot) in Belagavi and Bagalkote, Karnataka. The CLIP intervention (6 clusters) consisted of community engagement, community health workers (CHW) provided mobile health (mHeath)-guided clinical assessment, initial treatment, and referral to facility either urgently (<4h) or non-urgently (<24h), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of mHealth-guided CHW-provided contacts. 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity. All 14,783 recruited pregnancies (7839 intervention, 6944 control) were followed-up. The primary outcome did not differ between intervention and control arms (adjusted odds ratio (aOR) 0.92 [95% confidence interval 0.74, 1.15]; p=0.47; intraclass correlation coefficient 0.013). There were no intervention-related safety concerns following administration of either methyldopa or MgSO4, and 401 facility referrals. Compared with intervention arm women without CLIP contacts, those with ≥8 contacts suffered fewer stillbirths (aOR 0.19 [0.10, 0.35]; p<0.001), at the probable expense of survivable neonatal morbidity (aOR 1.39 [0.97, 1.99]; p=0.072). As implemented, solely community-level interventions focussed on pre-eclampsia did not improve outcomes in northwest Karnataka.

To reduce all-cause maternal and perinatal mortality and major morbidity through Lady Health Worker (LHW)-facilitated community engagement and early diagnosis, stabilization and referral of women with preeclampsia, an important contributor to adverse maternal and perinatal outcomes given delays in early detection and initial management. In the Pakistan Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial (NCT01911494), LHWs engaged the community, recruited pregnant women from 20 union councils (clusters), undertook mobile health-guided clinical assessment for preeclampsia, and referral to facilities after stabilization. The primary outcome was a composite of maternal, fetal and newborn mortality and major morbidity. We recruited 39,446 women in intervention (N=20,264) and control clusters (N=19,182) with minimal loss to follow-up (3∙7% vs. 4∙5%, respectively). The primary outcome did not differ between intervention (26·6%) and control (21·9%) clusters (adjusted odds ratio, aOR, 1∙20 [95% confidence interval 0∙84-1∙72]; p=0∙31). There was reduction in stillbirths (0·89 [0·81-0·99]; p=0·03), but no impact on maternal death (1·08 [0·69, 1·71]; p=0·74) or morbidity (1·12 [0·57, 2·16]; p=0·77); early (0·95 [0·82-1·09]; p=0·46) or late neonatal deaths (1·23 [0·97-1·55]; p=0·09); or neonatal morbidity (1·22 [0·77, 1·96]; p=0·40). Improvements in outcome rates were observed with 4-7 (p=0·015) and ≥8 (p<0·001) (vs. 0) CLIP contacts. The CLIP intervention was well accepted by the community and implemented by LHWs. Lack of effects on adverse outcomes could relate to quality care for mothers with pre-eclampsia in health facilities. Future strategies for community outreach must also be accompanied by health facility strengthening. The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337).

In Pakistan, an important contributor to maternal, fetal, and neonatal mortality is pregnancy hypertension. Its early detection and initial management may be amenable to task-sharing by Lady Health Workers (LHWs). To reduce by 20%, one or more of: maternal death/morbidity, stillbirth, or neonatal death/morbidity in the intervention clusters. The Pakistan Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised control trial (NCT01911494) recruited pregnant women in 20 union councils (clusters) in Sindh Province. The CLIP intervention (10 clusters) consisted of community engagement and LHW-provided mobile health-guided clinical assessment and initial treatment (MgSO4 or methyldopa, as appropriate), and referral by LHWs to facility for further management. Data were collected by quarterly household survey. Treatment effect was estimated by multi-level logistic regression modeling, adjusting for baseline cluster- and individual-level variables of prognostic significance. A priori defined secondary analyses included evaluation of temporal and dose-dependent treatment effects. Of 39,444 women recruited (20,264 women intervention, 19,180 control), losses to follow-up were 3·7% and 4·5%, respectively. The primary outcome did not differ between arms (N = 5381 women, 26·6% vs. N = 4195, 21·9%); adjusted odds ratio (aOR) 1·20, 95% confidence interval (CI) [0·84–1 72]. In both arms, an estimated reduction in the odds of primary outcome of 7.0% per quarter was observed (OR = 0.93, 95% CI 0.93,0.94, p < 0.001). In the intervention arm, the temporal trend-adjusted primary outcome rate decreased by 8.0% (aOR = 0.92 [0.90–0.95], p < 0.001) for each CLIP visit beyond three. While there was no difference in the primary outcome in intervention vs. control clusters, outcomes improved over time in all clusters, particularly maternal morbidity; suggesting that quarterly household surveillance served as an intervention. Receipt of more than three CLIP visits was associated with fewer adverse outcomes, suggesting a possible threshold of intervention that must be delivered to achieve positive health outcomes.

SummaryBackgroundBlood pressure measurement is a marker of antenatal care quality. In well resourced settings, lower blood pressure cutoffs for hypertension are associated with adverse pregnancy outcomes. We aimed to study the associations between blood pressure thresholds and adverse outcomes and the diagnostic test properties of these blood pressure cutoffs in low-resource settings.MethodsWe did a secondary analysis of data from 22 intervention clusters in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials (NCT01911494) in India (n=6), Mozambique (n=6), and Pakistan (n=10). We included pregnant women aged 15–49 years (12–49 years in Mozambique), identified in their community by trained community health workers, who had data on blood pressure measurements and outcomes. The trial was unmasked. Maximum blood pressure was categorised as: normal blood pressure (systolic blood pressure [sBP] <120 mm Hg and diastolic blood pressure [dBP] <80 mm Hg), elevated blood pressure (sBP 120–129 mm Hg and dBP <80 mm Hg), stage 1 hypertension (sBP 130–139 mm Hg or dBP 80–89 mm Hg, or both), non-severe stage 2 hypertension (sBP 140–159 mm Hg or dBP 90–109 mm Hg, or both), or severe stage 2 hypertension (sBP ≥160 mm Hg or dBP ≥110 mm Hg, or both). We classified women according to the maximum blood pressure category reached across all visits for the primary analyses. The primary outcome was a maternal, fetal, or neonatal mortality or morbidity composite. We estimated dose-response relationships between blood pressure category and adverse outcomes, as well as diagnostic test properties.FindingsBetween Nov 1, 2014, and Feb 28, 2017, 21 069 women (6067 in India, 4163 in Mozambique, and 10 839 in Pakistan) contributed 103 679 blood pressure measurements across the three CLIP trials. Only women with non-severe or severe stage 2 hypertension, as discrete diagnostic categories, experienced more adverse outcomes than women with normal blood pressure (risk ratios 1·29–5·88). Using blood pressure categories as diagnostic thresholds (women with blood pressure within the category or any higher category vs those with blood pressure in any lower category), dose-response relationships were observed between increasing thresholds and adverse outcomes, but likelihood ratios were informative only for severe stage 2 hypertension and maternal CNS events (likelihood ratio 6·36 [95% CI 3·65–11·07]) and perinatal death (5·07 [3·64–7·07]), particularly stillbirth (8·53 [5·63–12·92]).InterpretationIn low-resource settings, neither elevated blood pressure nor stage 1 hypertension were associated with maternal, fetal, or neonatal mortality or morbidity adverse composite outcomes. Only the threshold for severe stage 2 hypertension met diagnostic test performance standards. Current diagnostic thresholds for hypertension in pregnancy should be retained.FundingUniversity of British Columbia, the Bill & Melinda Gates Foundation.

In resource-constrained settings where the neonatal mortality rate (NMR) is high due to preventable causes and health systems are underused, community-based interventions can increase newborn survival by improving health care practices. To develop and evaluate the effectiveness of a community-based maternal and newborn care services package to reduce perinatal and neonatal mortality in rural Pakistan. This cluster randomized clinical trial was conducted between November 1, 2012, and December 31, 2013, in district Rahim Yar Khan in the province of Punjab. A cluster was defined as an administrative union council. Any consenting pregnant resident of the study area, regardless of gestational age, was enrolled. An ongoing pregnancy surveillance system identified 12 529 and 12 333 pregnancies in the intervention and control clusters, respectively; 9410 pregnancies were excluded from analysis due to continuation of pregnancy at the end of the study, loss to follow-up, or miscarriage. Participants were followed up until the 40th postpartum day. Statistical analysis was performed from January to May 2014. A maternal and newborn health pack, training for community- and facility-based health care professionals, and community mobilization through counseling and education sessions. The primary outcome was perinatal mortality, defined as stillbirths per 1000 births and neonatal death within 7 days per 1000 live births. The secondary outcome was neonatal mortality, defined as death within 28 days of life per 1000 live births. Systematic random sampling was used to allocate 10 clusters each to intervention and control groups. Analysis was conducted on a modified intention-to-treat basis. For the control group vs the intervention group, the total number of households was 33 188 vs 34 315, the median number of households per cluster was 3092 (IQR, 3018-3467) vs 3469 (IQR, 3019-4075), the total population was 229 155 vs 234 674, the mean (SD) number of residents per household was 6.9 (9.5) vs 6.8 (9.6), the number of males per 100 females (ie, the sex ratio) was 104.2 vs 103.7, and the mean (SD) number of children younger than 5 years per household was 1.0 (4.2) vs 1.0 (4.3). Altogether, 7598 births from conrol clusters and 8017 births from intervention clusters were analyzed. There was no significant difference in perinatal mortality between the intervention and control clusters (rate ratio, 0.86; 95% CI, 0.69-1.08; P = .19). The NMR was lower among the intervention than the control clusters (39.2/1000 live births vs 52.2/1000 live births; rate ratio, 0.75; 95% CI, 0.58-0.95; P = .02). The frequencies of antenatal visits and facility births were similar between the 2 groups. However, clean delivery practices were higher among intervention clusters than control clusters (63.2% [2284 of 3616] vs 13.2% [455 of 3458]; P < .001). Chlorhexidine use was also more common among intervention clusters than control clusters (55.9% [4271 of 7642] vs 0.3% [19 of 7203]; P < .001). This pragmatic cluster randomized clinical trial demonstrated a reduction in NMR that occurred in the background of improved household intrapartum and newborn care practices. However, the effect of the intervention on antenatal visits, facility births, and perinatal mortality rates was inconclusive, highlighting areas requiring further research. Nevertheless, the improvement in NMR underscores the effectiveness of community-based programs in low-resource settings. ClinicalTrials.gov Identifier: NCT01751945.

SummaryBackgroundIncomplete vital registration systems mean that causes of death during pregnancy and childbirth are poorly understood in low-income and middle-income countries. To inform global efforts to reduce maternal mortality, we compared physician review and computerised analysis of verbal autopsies (interpreting verbal autopsies [InterVA] software), to understand their agreement on maternal cause of death and circumstances of mortality categories (COMCATs) in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials.MethodsThe CLIP trials took place in India, Pakistan, and Mozambique, enrolling pregnant women aged 12–49 years between Nov 1, 2014, and Feb 28, 2017. 69 330 pregnant women were enrolled in 44 clusters (36 008 in the 22 intervention clusters and 33 322 in the 22 control clusters). In this secondary analysis of maternal deaths in CLIP, we included women who died in any of the 22 intervention clusters or 22 control clusters. Trained staff administered the WHO 2012 verbal autopsy after maternal deaths. Two physicians (and a third for consensus, if needed) reviewed trial surveillance data and verbal autopsies, and, in intervention clusters, community health worker-led visit data. They determined cause of death according to the WHO International Classification of Diseases-Maternal Mortality (ICD-MM). Verbal autopsies were also analysed by InterVA computer models (versions 4 and 5) to generate cause of death. COMCAT analysis was provided by InterVA-5 and, in India, by physician review of Maternal Newborn Health Registry data. Causes of death and COMCATs assigned by physician review, Inter-VA-4, and InterVA-5 were compared, with agreement assessed with Cohen's κ coefficient.FindingsOf 61 988 pregnancies with successful follow-up in the CLIP trials, 143 maternal deaths were reported (16 deaths in India, 105 in Pakistan, and 22 in Mozambique). The maternal death rate was 231 (95% CI 193–268) per 100 000 identified pregnancies. Most deaths were attributed to direct maternal causes (rather than indirect or undetermined causes as per ICD-MM classification), with fair to good agreement between physician review and InterVA-4 (κ=0·56 [95% CI 0·43–0·66]) or InterVA-5 (κ=0·44 [0·30–0·57]), and InterVA-4 and InterVA-5 (κ=0·72 [0·60–0·84]). The top three causes of death were the same by physician review, InterVA-4, and InterVA-5 (ICD-MM categories obstetric haemorrhage, non-obstetric complications, and hypertensive disorders); however, attribution of individual patient deaths to obstetric haemorrhage varied more between methods (physician review, 38 [27%] deaths; InterVA-4, 69 [48%] deaths; and InterVA-5, 82 [57%] deaths), than did attribution to non-obstetric causes (physician review, 39 [27%] deaths; InterVA-4, 37 [26%] deaths; and InterVA-5, 28 [20%] deaths) or hypertensive disorders (physician review, 23 [16%] deaths; InterVA-4, 25 [17%] deaths; and InterVA-5, 24 [17%] deaths). Agreement for all nine ICD-MM categories was fair for physician review versus InterVA-4 (κ=0·48 [0·38–0·58]), poor for physician review versus InterVA-5 (κ=0·36 [0·27–0·46]), and good for InterVA-4 versus InterVA-5 (κ=0·69 [0·59–0·79]). The most commonly assigned COMCATs by InterVA-5 were emergencies (68 [48%] of 143 deaths) and health systems (62 [43%] deaths), and by physician review (India only) were health systems (seven [44%] of 16 deaths) and inevitability (five [31%] deaths); agreement between InterVA-5 and physician review (India data only) was poor (κ=0·04 [0·00–0·15]).InterpretationOur findings indicate that InterVA-5 is less accurate than InterVA-4 at ascertaining causes and circumstances of maternal death, when compared with physician review. Our results suggest a need to improve the next iteration of InterVA, and for researchers and clinicians to preferentially use InterVA-4 when recording maternal deaths.FundingUniversity of British Columbia (grantee of the Bill & Melinda Gates Foundation).

To test the hypothesis that a screening and treatment intervention for early cryptococcal infection would improve survival among HIV-infected individuals with low CD4 cell counts. Newly enrolled patients at Family AIDS Care and Education Services (FACES) in Kenya with CD4≤100 cells/μl were tested for serum cryptococcal antigen (sCrAg). Individuals with sCrAg titre≥1:2 were treated with high-dose fluconazole. Cox proportional hazard models of Kaplan-Meier curves were used to compare survival among individuals with CD4≤100 cells/μl in the intervention and historical control groups. The median age was 34years [IQR: 29,41], 54% were female, and median CD4 was 43 cells/μl [IQR: 18,71]. Follow-up time was 1224 person-years. In the intervention group, 66% (514/782) were tested for sCrAg; of whom, 11% (59/514) were sCrAg positive. Mortality was 25% (196/782) in the intervention group and 25% (191/771) in the control group. There was no significant difference between the intervention and control group in overall survival [hazard ratio (HR): 1.1 (95%CI:0.9,1.3)] or three-month survival [HR: 1.0 (95%CI:0.8,1.3)]. Within the intervention group, sCrAg-positive individuals had significantly lower survival rates than sCrAg-negative individuals [HR:1.8 (95%CI: 1.0, 3.0)]. A screening and treatment intervention to identify sCrAg-positive individuals and treat them with high-dose fluconazole did not significantly improve overall survival among HIV-infected individuals with CD4 counts≤100 cells/μl compared to a historical control, perhaps due to intervention uptake rates or poor efficacy of high-dose oral fluconazole.

218. Implementation of the PIERS on the Move mobile health app in the Community Level Interventions for Pre-eclampsia trials

Background: Most estimates of pregnancy hypertension in lessdeveloped countries are from hospital-based cross-sectional surveys and are probably over-estimates. We aimed to estimate population-based rates by standardised methods in intervention clusters of the Community-Level Interventions in Pre-eclampsia (CLIP) cluster randomised trials (NCT01911494). Methods: In study regions, all pregnant women were CLIP-eligible and identified in their homes or local primary health centres (2013-17). This analysis includes women in intervention clusters who both received at least one community health worker (CHW) visit and had delivered by trial end. Trained CHWs provided supplementary hypertension-oriented care that included standardised blood pressure (BP) measurement using a semiautomated device validated in pregnancy. Based on gestational age at presentation, hypertension (BP ≥140/90mmHg) was 'chronic' (<20 weeks) or 'gestational' (≥20 weeks). 'Pre-eclampsia' was gestational hypertension with ≥1 proteinuria or a relevant end-organ complication. A multi-level regression model was used to compare hypertension rates and types between countries (p<0·05 significant). Results: In 28,420 pregnancies (27 clusters), pregnancy hypertension incidence was significantly lower in Pakistan (9·3%) than India (10·3%), Mozambique (10·9%), or Nigeria (10·2%) (p=0·001). Most hypertension was diastolic only (46·4% India, 72·7% Pakistan, 61·3% Mozambique, and 63·3% Nigeria). Chronic hypertension was more common in sub-Saharan Africa (2·5% Mozambique, 2·8% Nigeria) than South Asia (1·2% India, 1·5%Pakistan) (p<0·001). At first presentation with elevated BP, gestational hypertension was most common, particularly in Mozambique (8·4%) compared with India (6·9%), Pakistan (6·5%) or Nigeria (7·1%) (p<0·001); preeclampsia was most common in India (3·8%), followed by Nigeria (3·0%), Pakistan (2·4%), and Mozambique (2·3%) (p<0·001). Women rarely presented with eclampsia (1 in India and 3 in Nigeria). Conclusions: Pregnancy hypertension incidence (overall and by type) are at least as high in less-, compared with more-, developed settings. Most women present with gestational hypertension, which is amenable to surveillance and timed delivery aimed at decreasing morbidity and mortality. Clinical Trial Number: (NCT01911494) Funding Statement: This study was funded by the University of British Columbia, a grantee of the Bill & Melinda Gates Foundation, through the PRE-EMPT initiative (grant number OPP1017337). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The CLIP trials were approved by the University of British Columbia Research Ethics Board as the Coordinating Centre (H12-03497) and within each country (MDC/IECHSR/2013-14/A, India; 2590-Obs-ERC13 Pakistan; 219/CNBS/13 Mozambique; OOUTH/DA.326/T/1/ Nigeria).

Exclusive breastfeeding promotion by peer counsellors in sub-Saharan Africa (PROMISE-EBF): a cluster-randomised trial

BackgroundIron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied.MethodsThe study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding.ResultsOf 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31–3.56), moderate (RR 2.37, 95% CI 1.56–3.59), and severe (RR 5.70, 95% CI 3.00–10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia.ConclusionIn Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.

Post-partum family planning services can prevent maternal and child morbidity and mortality in low-resource settings. We assessed the effect of a family planning intervention package on modern contraceptive use at 12 months post partum in predominantly rural Burkina Faso. Yam Daabo was a two group, multi-intervention, single-blinded, cluster randomised controlled trial. Primary health-care centres were randomly allocated to intervention or control clusters in a 1:1 ratio with only data analysts masked to the allocation assignment. Interventions comprised refresher training for the provider, a counselling tool, supportive supervision, availability of contraceptive services 7 days a week, client appointment cards, and invitation letters for partners. The primary outcome was modern contraceptive prevalence at 12 months, and secondary outcomes were modern contraceptive prevalence at 6 weeks and 6 months post partum. Analysis was by modified intention to treat. Prevalence ratios were adjusted for cluster effects and baseline characteristics. This study was registered with the Pan-African Clinical Trials Registry (PACTR201609001784334). From July 27-Oct 17, 2016, eight clinics were randomised and 571 women were enrolled and allocated: 286 to four intervention clusters and 285 to four control clusters. Of these, 523 completed the 12-month study exit interview (260 in the intervention group, 263 in the control group) and 523 were included in the intention-to-treat analysis. At 12 months, modern contraceptive prevalence was 55% among women who received the package and 29% among those who received routine care in control clusters (adjusted prevalence ratio 1·79, 95% CI 1·30-2·47). Significant differences in modern contraceptive prevalence were also seen between intervention and control groups at 6 weeks (42% and 10%, respectively; adjusted prevalence ratio 3·88, 95% CI 1·46-10·35) and 6 months (59% and 24%, respectively; 2·31, 1·44-3·71). A package of six low-technology interventions, aimed at strengthening existing primary health-care services and enhancing demand for these services, can effectively increase modern contraceptive use for up to a year post partum in rural settings in Burkina Faso and has the potential to be suitable in similar settings in this country and others. Government of France.

To explore the correlation between the elevated expression of cytokines under the induction of Poly(I:C) (polycytidylic acid) in maternal hosts and the abnormal behaviors of adult offsprings and understand the intervening effects of nuclear factor NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC). Poly(I:C) or saline was administered to model the maternal infection during early pregnancy in rats. And the expression of cytokines was blocked with PDTC. The maternal levels of tumor necrosis factor alpha and interleukin-10 were determined by ELISA (enzyme-linked immunosorbent assay). The adult offsprings on different treatments were then compared with regards to prepulse inhibition (PPI), passive avoidance and active avoidance. After the administration of Poly(I:C), there was an elevated levels of serum cytokines as shown by the markedly increased serum levels of IL-10 and TNF-α. The serum levels of IL-10 and TNF-α in the model group were significantly higher than those in the control group [(18.26 ± 1.52) pg/ml, (119.64 ± 16.42) pg/ml vs. (0.16 ± 0.13) pg/ml and (11.21 ± 1.81) pg/ml]. The elevation was partly blocked by PDTC. The serum levels of IL-10 and TNF-α in the intervention group [(12.64 ± 2.04) pg/ml and (30.34 ± 2.19) pg/ml respectively] were lower than those in the model group, but still higher than those in the control group. The psychotic-like phenotypes including defects in PPI, passive avoidance and active avoidance were observed in Poly(I:C)-treated offsprings. Such an effect was blunted by the PDTC intervention. The PPI results demonstrated that the PP₂ and PP₈ difference between rats in 3 groups were statistically significant, with a lower PPI value in the model group than in the intervention group, in the intervention group than in the control group and much lower in the model group than in the control group. PP4 was lower in the model group than that in the intervention group, and also lower in the model group than in the control group. There was no significant difference between the control group and the intervention group. The passive avoidance results indicated that T1 was higher in the model group than in the control and intervention groups and there was no statistical difference between the control and intervention groups. T2 was lower in the model group than in the control and intervention groups and there was no statistical difference between the control and intervention groups. And the active avoidance test results showed that total conditioned reflex times of the control group was higher than those of the intervention and model groups. No statistical difference was found between the intervention and model groups. Total reflex rate of the control group was higher than that of the intervention and model groups. No statistical difference was found between the intervention and model groups. PDTC can interfere with neural developmental disorder of adult offsprings through blunting the cytokine-mediated maternal immune response.

Effectiveness of an integrated intimate partner violence and HIV prevention intervention in Rakai, Uganda: analysis of an intervention in an existing cluster randomised cohort.