Safety of COVID-19 vaccines during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Assessment of COVID-19 vaccines safety during pregnancy is urgently needed. METHODS: We conducted a systematic review and meta-analysis to evaluate the safety of COVID-19 vaccines, including their components and technological platforms used in other vaccines during pregnancy and animal studies to complement direct evidence. We searched literature databases from its inception to September 2021 without language restriction, COVID-19 vaccine websites, and reference lists of other systematic reviews and the included studies. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42021234185). RESULTS: We retrieved 8,837 records from the literature search; 71 studies were included, involving 17,719,495 pregnant persons and 389 pregnant animals. Most studies (94%) were conducted in high-income countries, were cohort studies (51%), and 15% were classified as high risk of bias. We identified nine COVID-19 vaccine studies, seven involving 309,164 pregnant persons, mostly exposed to mRNA vaccines. Among non-COVID-19 vaccines, the most frequent exposures were AS03 and aluminum-based adjuvants. A meta-analysis of studies that adjusted for potential confounders showed no association with adverse outcomes, regardless of the vaccine or the trimester of vaccination. Neither the reported rates of adverse pregnancy outcomes nor reactogenicity exceeded expected background rates, which was the case for ASO3- or aluminum-adjuvanted non-COVID-19 vaccines in the proportion meta-analyses of uncontrolled studies/arms. The only exception was postpartum hemorrhage after COVID-19 vaccination (10.40%; 95% CI: 6.49-15.10%), reported by two studies; however, the comparison with non-exposed pregnant persons, available for one study, found non-statistically significant differences (adjusted OR 1.09; 95% CI 0.56-2.12). Animal studies showed consistent results with studies in pregnant persons. CONCLUSION: We found no safety concerns for currently administered COVID-19 vaccines during pregnancy. Additional experimental and real-world evidence could enhance vaccination coverage. Robust safety data for non-mRNA-based COVID-19 vaccines are still needed.

Safety, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for systematic review and meta analysis.

INTRODUCTION: Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding the safety of these vaccines for the pregnant person and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, reactogenicity, immunogenicity, and efficacy of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review and meta-analysis of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide the information necessary to help guide vaccine policy decisions. METHODS AND ANALYSIS: We aim to conduct a living systematic review and meta-analysis based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety, efficacy, and effectiveness of COVID-19 vaccines in pregnant persons, including neonatal outcomes. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence.

Understanding perinatal patient's health preferences and patient-provider relationships to prevent congenital syphilis in California and Louisiana.

BACKGROUND: Congenital syphilis (CS) has reemerged as a global maternal and child health crisis. Kern County, California and East Baton Rouge Parish, Louisiana are among the highest CS morbidity regions in the United States. We previously reported on social-ecological and structural barriers to prenatal care and maternal syphilis testing and treatment in these two regions. The aim of this study was to examine perinatal patient's health preferences and perceptions of patient-provider relationships in the prenatal care clinic setting. METHODS: Between May 2018 and January 2019 we conducted 20 in-depth qualitative interviews with prenatal providers and 8 focus group discussions with pregnant and postpartum individuals in Kern County and East Baton Rouge Parish. We applied an adapted health services framework to analyze participants' understanding of health disparities and vulnerable populations; perinatal patient's health and prenatal care preferences; and participants' perspectives of clinical encounters in the context of prenatal care and maternal syphilis testing and treatment. RESULTS: Site-specific determinants of syphilis infection emerged but participants from both locations felt CS prevention efforts should be prioritized among youth, racial/ethnic minority populations, people experiencing socioeconomic limitations and people with other commonly occurring health conditions. Although perinatal patients expressed clear health preferences, they reported inconsistent receipt of respectful, patient-centered care. Inconsistencies were connected with limited ethnic and cultural competence among providers, and implicit, negative attitudes toward patients using substances, experiencing homelessness, or engaging in sex work. Providers clearly aimed to offer high quality prenatal care. However, some clinic and health systems level factors were thought to reduce positive and communicative patient-provider relationships, contributing to gaps in use of prenatal care and syphilis testing and treatment. CONCLUSIONS: Our findings suggest that interventions tailored to address setting-specific determinants (including clinic and health system factors) of disparities in CS risk could improve pregnant people's access to prenatal care and ensure they and their sex partners receive timely syphilis screening and treatment. We recommend all prenatal care providers receive training on how to identify and mitigate implicit biases and provide competent and compassionate patient-centered care.

Safety of components and platforms of COVID-19 vaccines considered for use in pregnancy: A rapid review.

BACKGROUND: Rapid assessment of COVID-19 vaccine safety during pregnancy is urgently needed. METHODS: We conducted a rapid systematic review, to evaluate the safety of COVID-19 vaccines selected by the COVID-19 Vaccines Global Access-Maternal Immunization Working Group in August 2020, including their components and their technological platforms used in other vaccines for pregnant persons. We searched literature databases, COVID-19 vaccine pregnancy registries, and explored reference lists from the inception date to February 2021 without language restriction. Pairs of reviewers independently selected studies through COVIDENCE, and performed the data extraction and the risk of bias assessment. Discrepancies were resolved by consensus. Registered on PROSPERO (CRD42021234185). RESULTS: We retrieved 6757 records and 12 COVID-19 pregnancy registries from the search strategy; 38 clinical and non-clinical studies (involving 2,398,855 pregnant persons and 56 pregnant animals) were included. Most studies (89%) were conducted in high-income countries and were cohort studies (57%). Most studies (76%) compared vaccine exposures with no exposure during the three trimesters of pregnancy. The most frequent exposure was to AS03 adjuvant, in the context of A/H1N1 pandemic influenza vaccines, (n = 24) and aluminum-based adjuvants (n = 11). Only one study reported exposure to messenger RNA in lipid nanoparticles COVID-19 vaccines. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03), corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted, given their novelty. Our findings support current WHO guidelines recommending that pregnant persons may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.

Safety of COVID-19 vaccines, their components or their platforms for pregnant women: A rapid review.

BACKGROUND: Pregnant women with COVID-19 are at an increased risk of severe COVID-19 illness as well as adverse pregnancy and birth outcomes. Many countries are vaccinating or considering vaccinating pregnant women with limited available data about the safety of this strategy. Early identification of safety concerns of COVID-19 vaccines, including their components, or their technological platforms is therefore urgently needed. METHODS: We conducted a rapid systematic review, as the first phase of an ongoing full systematic review, to evaluate the safety of COVID-19 vaccines in pregnant women, including their components, and their technological platforms (whole virus, protein, viral vector or nucleic acid) used in other vaccines, following the Cochrane methods and the PRISMA statement for reporting (PROSPERO-CRD42021234185).We searched literature databases, COVID-19 and pregnancy registries from inception February 2021 without time or language restriction and explored the reference lists of relevant systematic reviews retrieved. We selected studies of any methodological design that included at least 50 pregnant women or pregnant animals exposed to the vaccines that were selected for review by the COVAX MIWG in August 2020 or their components or platforms included in the COVID-19 vaccines, and evaluated adverse events during pregnancy and the neonatal period.Pairs of reviewers independently selected studies through the COVIDENCE web software and performed the data extraction through a previously piloted online extraction form. Discrepancies were resolved by consensus. RESULTS: We identified 6768 records, 256 potentially eligible studies were assessed by full-text, and 37 clinical and non-clinical studies (38 reports, involving 2,397,715 pregnant women and 56 pregnant animals) and 12 pregnancy registries were included.Most studies (89%) were conducted in high-income countries. The most frequent study design was cohort studies (n=21), followed by surveillance studies, randomized controlled trials, and registry analyses. Most studies (76%) allowed comparisons between vaccinated and unvaccinated pregnant women (n=25) or animals (n=3) and reported exposures during the three trimesters of pregnancy.The most frequent exposure was to AS03 adjuvant in the context of A/H1N1 pandemic influenza vaccines (n=24), followed by aluminum-based adjuvants (n=11). Aluminum phosphate was used in Respiratory Syncytial Virus Fusion candidate vaccines (n=3) and Tdap vaccines (n=3). Different aluminum-based adjuvants were used in hepatitis vaccines. The replication-deficient simian adenovirus ChAdOx1 was used for a Rift Valley fever vaccine. Only one study reported exposure to messenger RNA (mRNA) COVID-19 vaccines that also used lipid nanoparticles. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03) - corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines that were selected for review by the COVAX MIWG or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted given their novelty. Our findings support current WHO guidelines recommending that pregnant women may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.

Measurement error, microcephaly prevalence and implications for Zika: an analysis of Uruguay perinatal data.

BACKGROUND AND OBJECTIVE: The Zika virus outbreak has drawn attention to microcephaly, whose definition is based on head circumference measuring below a percentile or number of SDs below the mean. The objective of this analysis was to assess how differences in measurement precision might affect prevalence and trends of microcephaly. METHODS: Data from all births in Uruguay during 2010-2015 were obtained from the Perinatal Information System. The prevalence of births with microcephaly was calculated based on head circumference measurement at birth applying the INTERGROWTH-21st standards for sex and gestational age, and compared by method of ascertaining gestational age. RESULTS: Rounding and digit preference was observed: 74% of head circumference measurements were reported as a whole centimetre value. The prevalence of births varied substantially by the criterion used to define microcephaly (<3 SD, <2 SD, <3rd percentile for gestational age) and could be halved or doubled based on adding or subtracting a half-centimetre from all reported head circumference measurements. If 4 days were added to gestational age calculations, rather than using completed gestational weeks (without days) for gestational age reporting, the prevalence was 1.7-2 times higher. DISCUSSION: Rounding in measurement of head circumference and reporting preferences of gestational age may have contributed to a lower prevalence of microcephaly than expected in this population. Differences in head circumference measurement protocols and gestational age dating have the potential to affect the prevalence of babies reported with microcephaly, and this limitation should be acknowledged when interpreting head circumference data collected for surveillance.

An approach to identify a minimum and rational proportion of caesarean sections in resource-poor settings: a global network study.

BACKGROUND: Caesarean section prevalence is increasing in Asia and Latin America while remaining low in most African regions. Caesarean section delivery is effective for saving maternal and infant lives when they are provided for medically-indicated reasons. On the basis of ecological studies, caesarean delivery prevalence between 9% and 19% has been associated with better maternal and perinatal outcomes, such as reduced maternal land fetal mortality. However, the specific prevalence of obstetric and medical complications that require caesarean section have not been established, especially in low-income and middle-income countries (LMICs). We sought to provide information to inform the approach to the provision of caesarean section in low-resource settings. METHODS: We did a literature review to establish the prevalence of obstetric and medical conditions for six potentially life-saving indications for which caesarean section could reduce mortality in LMICs. We then analysed a large, prospective population-based dataset from six LMICs (Argentina, Guatemala, Kenya, India, Pakistan, and Zambia) to determine the prevalence of caesarean section by indication for each site. We considered that an acceptable number of events would be between the 25th and 75th percentile of those found in the literature. FINDINGS: Between Jan 1, 2010, and Dec 31, 2013, we enrolled a total of 271 855 deliveries in six LMICs (seven research sites). Caesarean section prevalence ranged from 35% (3467 of 9813 deliveries in Argentina) to 1% (303 of 16 764 deliveries in Zambia). Argentina's and Guatemala's sites all met the minimum 25th percentile for five of six indications, whereas sites in Zambia and Kenya did not reach the minimum prevalence for caesarean section for any of the indications. Across all sites, a minimum overall caesarean section of 9% was needed to meet the prevalence of the six indications in the population studied. INTERPRETATION: In the site with high caesarean section prevalence, more than half of the procedures were not done for life-saving conditions, whereas the sites with low proportions of caesarean section (below 9%) had an insufficient number of caesarean procedures to cover those life-threatening causes. Attempts to establish a minimum caesarean prevalence should go together with focusing on the life-threatening causes for the mother and child. Simple methods should be developed to allow timely detection of life-threatening conditions, to explore actions that can remedy those conditions, and the timely transfer of women with those conditions to health centres that could provide adequate care for those conditions. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Barriers and facilitators to the implementation of antenatal syphilis screening and treatment for the prevention of congenital syphilis in the Democratic Republic of Congo and Zambia: results of qualitative formative research.

BACKGROUND: The impact of untreated syphilis during pregnancy on neonatal health remains a major public health threat worldwide. Given the high prevalence of syphilis during pregnancy in Zambia and Democratic Republic of Congo (DRC), the Preventive Congenital Syphilis Trial (PCS Trial), a cluster randomized trial, was proposed to increase same-day screening and treatment of syphilis during antenatal care visits. To design an accepted and feasible intervention, we conducted a qualitative  formative research. Our objective was to identify context-specific  barriers and facilitators to the implementation of antenatal screening and treatment during pregnancy. METHODS: Qualitative research included in-depth semi-structured interviews with clinic administrators, group interviews with health care providers, and focus groups with pregnant women in primary care clinics (PCCs) in Kinshasa (DRC) and Lusaka (Zambia). RESULTS: A total of 112 individuals participated in the interviews and focus groups. Barriers for the implementation of syphilis testing and treatment were identified at the a) system level: fragmentation of the health system, existence of ANC guidelines in conflict with proposed intervention, poor accessibility of clinics (geographical and functional), staff and product shortages at the PCCs; b) healthcare providers' level: lack of knowledge and training about evolving best practices, reservations regarding same-day screening and treatment; c) Pregnant women level: late enrollment in ANC, lack of knowledge about consequences and treatment of syphilis, and stigma. Based on these results, we developed recommendations for the design of the PCS Trial intervention. CONCLUSION: This research allowed us to identify barriers and facilitators to improve the feasibility and acceptability of a behavioral intervention. Formative research is a critical step in designing appropriate and effective interventions by closing the "know-do gap".

The global network antenatal corticosteroids trial: impact on stillbirth.

BACKGROUND: Antenatal corticosteroids are commonly used to reduce neonatal mortality, but most research to date has been in high-resource settings and few studies have evaluated its impact on stillbirth. In the Antenatal Corticosteroids Trial (ACT), a multi-country trial to assess impact of a multi-faceted intervention including antenatal corticosteroids to reduce neonatal mortality associated with preterm birth, we found an overall increase in 28-day neonatal mortality and stillbirth associated with the intervention. METHODS: The ACT was a cluster-randomized trial conducted in 102 clusters across 7 research sites in 6 countries (India [2 sites], Pakistan, Zambia, Kenya, Guatemala and Argentina), comparing an intervention to train birth attendants at all levels of the health system to identify women at risk of preterm birth, administer corticosteroids and refer women at risk. Because of inadequate gestational age dating, the <5(th) percentile birth weight was used as a proxy for preterm birth. A pre-specified secondary outcome of the trial was stillbirth. RESULTS: After adjusting for the pre-trial imbalance in stillbirth rates, the ACT intervention was associated with a non-significant increased risk of stillbirth (aRR 1.08, 95 % CI, 0.99-1.17, p-0.073). Additionally, the stillbirth rate was higher in the term births (1.20 95 % CI 1.06-1.37, 0.004) and among those with signs of maceration (RR 1.18 (1.04-1.35), p = 0.013) in the intervention vs. control clusters. Differences in obstetric care favored the control clusters and maternal infection was likely more common in the intervention clusters. CONCLUSIONS: In this pragmatic trial, limited data were available to identify the causes of the increase in stillbirths in the intervention clusters. A higher rate of stillbirth in the intervention clusters prior to the trial, differences in obstetric care and an increase in maternal infection are potential explanations for the observed increase in stillbirths in the intervention clusters during the trial. TRIAL REGISTRATION: clinicaltrials.gov (NCT01084096).

The Antenatal Corticosteroids Trial (ACT)'s explanations for neonatal mortality - a secondary analysis.

BACKGROUND: The Antenatal Corticosteroid Trial assessed the feasibility, effectiveness, and safety of a multifaceted intervention to increase the use of antenatal corticosteroids (ACS) in mothers at risk of preterm birth at all levels of care in low and middle-income countries. The intervention effectively increased the use of ACS but was associated with an overall increase in neonatal deaths. We aimed to explore plausible pathways through which this intervention increased neonatal mortality. METHODS: We conducted a series of secondary analyses to assess whether ACS or other components of the multifaceted intervention that might have affected the quality of care contributed to the increased mortality observed: 1) we compared the proportion of neonatal deaths receiving ACS between the intervention and control groups; 2) we compared the antenatal and delivery care process in all births between groups; 3) we compared the rates of possible severe bacterial infection between groups; and 4) we compared the frequency of factors related to ACS administration or maternal high risk conditions at administration between the babies who died and those who survived 28 days among all births in the intervention group identified as high risk for preterm birth and received ACS. RESULTS: The ACS exposure among the infants who died up to 28 days was 29 % in the intervention group compared to 6 % in controls. No substantial differences were observed in antenatal and delivery care process between groups. The risk of pSBI plus neonatal death was significantly increased in intervention clusters compared to controls (2.4 % vs. 2.0 %, adjusted RR 1.17, 95 % CI 1.04-1.30, p = 0.008], primarily for infants with birth weight at or above the 25(th) percentile. Regarding factors related to ACS administration, term infants who died were more likely to have mothers who received ACS within 7 days of delivery compared to those who survived 28 days (26.5 % vs 17.9 %, p = 0.014), and their mothers were more likely to have been identified as high risk for hypertension and less likely for signs of preterm labor. CONCLUSIONS: These results suggest that ACS more than other components of the intervention may have contributed to the overall increased neonatal mortality. ACS may have also been involved in the observed increased risk of neonatal infection and death. Further trials are urgently needed to clarify the effectiveness and safety of ACS on neonatal health in low resource settings.

The Antenatal Corticosteroids Trial (ACT): a secondary analysis to explore site differences in a multi-country trial.

BACKGROUND: The Antenatal Corticosteroid Trial (ACT) assessed the feasibility, effectiveness, and safety of a multifaceted intervention to increase the use of antenatal corticosteroids (ACS) in mothers at risk of preterm birth at all levels of care in low and middle-income countries. The intervention effectively increased the use of ACS but had no overall impact on neonatal mortality in the targeted <5(th) percentile birth weight infants. Being in the intervention clusters was also associated with an overall increase in neonatal deaths. We sought to explore plausible pathways through which this intervention increased neonatal mortality. METHODS: We conducted secondary analyses to assess site differences in outcome and potential explanations for the differences in outcomes if found. By site, and in the intervention and control clusters, we evaluated characteristics of the mothers and care systems, the proportion of the <5(th) percentile infants and the overall population that received ACS, the rates of possible severe bacterial infection (pSBI), determined from clinical signs, and neonatal mortality rates. RESULTS: There were substantial differences between the sites in both participant and health system characteristics, with Guatemala and Argentina generally having the highest levels of care. In some sites there were substantial differences in the health system characteristics between the intervention and control clusters. The increase in ACS in the intervention clusters was similar among the sites. While overall, there was no difference in neonatal mortality among <5(th) percentile births between the intervention and control clusters, Guatemala and Pakistan both had significant reductions in neonatal mortality in the <5(th) percentile infants in the intervention clusters. The improvement in neonatal mortality in the Guatemalan site in the <5(th) percentile infants was associated with a higher level of care at the site and an improvement in care in the intervention clusters. There was a significant increase overall in neonatal mortality in the intervention clusters compared to the control. Across sites, this increase in neonatal mortality was statistically significant and most apparent in the African sites. This increase in neonatal mortality was accompanied by a significant increase in pSBI in the African sites. CONCLUSIONS: The improvement in neonatal mortality in the Guatemalan site in the <5(th) percentile infants was associated with a higher level of care and an improvement in care in the intervention clusters. The increase in neonatal mortality in the intervention clusters across all sites was largely driven by the poorer outcomes in the African sites, which also had an increase in pSBI in the intervention clusters. We emphasize that these results come from secondary analyses. Additional prospective studies are needed to assess the effectiveness and safety of ACS on neonatal health in low resource settings. TRIAL REGISTRATION: clinicaltrials.gov (NCT01084096).

Use of antenatal corticosteroids at health facilities and communities in low-and-middle income countries.

BACKGROUND: Antenatal corticosteroids (ACS) for women at high risk of preterm birth is an effective intervention to reduce neonatal mortality among preterm babies delivered in hospital settings, but has not been widely used in low-middle resource settings. We sought to assess the rates of ACS use at all levels of health care in low and middle income countries (LMIC). METHODS: We assessed rates of ACS in 7 sites in 6 LMIC participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Global Network for Women and Children's Health Research Antenatal Corticosteroids Trial (ACT), a cluster-randomized trial to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of ACS. We conducted this analysis using data from the control clusters, which did not receive any components of the intervention and intended to follow usual care. We included women who delivered an infant with a birth weight <5th percentile, a proxy for preterm birth, and were enrolled in the Maternal Newborn Health (MNH) Registry between October 2011 and March 2014 in all clusters. A survey of the site investigators regarding existing policies on ACS in health facilities and for health workers in the community was part of pre-trial activities. RESULTS: Overall, of 51,523 women delivered in control clusters across all sites, the percentage of <5th percentile babies ranged from 3.5 % in Kenya to 10.7 % in Pakistan. There was variation among the sites in the use of ACS at all hospitals and among those hospitals having cesarean section and neonatal care capabilities (bag and mask and oxygen or mechanical ventilation). Rates of ACS use for <5th percentile babies in all hospitals ranged from 3.8 % in the Kenya sites to 44.5 % in the Argentina site, and in hospitals with cesarean section and neonatal care capabilities from 0 % in Zambia to 43.5 % in Argentina. ACS were rarely used in clinic or home deliveries at any site. Guidelines for ACS use at all levels of the health system were available for most of the sites. CONCLUSION: Our study reports an overall low utilization of ACS among mothers of <5th percentile infants in hospital and clinic deliveries in LMIC. TRIAL REGISTRATION: clinicaltrials.gov ( NCT01084096 ).

A Multifaceted Strategy to Implement Brief Smoking Cessation Counseling During Antenatal Care in Argentina and Uruguay: A Cluster Randomized Trial.

INTRODUCTION: Argentina and Uruguay have a high prevalence of smoking during pregnancy. However, and despite national recommendations, pregnant women are not routinely receiving cessation counseling during antenatal care (ANC). We evaluated a multifaceted strategy designed to increase the frequency of pregnant women who received a brief smoking cessation counseling based on the 5As (Ask, Advise, Assess, Assist, and Arrange). METHODS: We randomly assigned (1:1) 20 ANC clusters in Buenos Aires, Argentina and Montevideo, Uruguay to receive a multifaceted intervention to implement brief smoking cessation counseling into routine ANC, or to receive no intervention. The primary outcome was the frequency of women who recalled receiving the 5As during ANC at more than one visit. Frequency of women who smoked until the end of pregnancy, and attitudes and readiness of ANC providers towards providing counseling were secondary outcomes. Women's outcomes were measured at baseline and at the end of the 14- to 18-month intervention, by administering questionnaires at the postpartum hospital stay. Self-reported cessation was verified with saliva cotinine. The trial took place between October 03, 2011 and November 29, 2013. RESULTS: The rate of women who recalled receiving the 5As increased from 14.0% to 33.6% in the intervention group (median rate change, 22.1%), and from 10.8% to 17.0% in the control group (median rate change, 4.6%; P = .001 for the difference in change between groups). The effect of the intervention was larger in Argentina than in Uruguay. The proportion of women who continued smoking during pregnancy was unchanged at follow-up in both groups and the relative difference between groups was not statistically significant (ratio of odds ratios 1.16, 95% CI: 0.98-1.37; P = .086). No significant changes were observed in knowledge, attitudes, and self-confidence of ANC providers. CONCLUSIONS: The intervention showed a moderate effect in increasing the proportion of women who recalled receiving the 5As, with a third of women receiving counseling in more than one visit. However, the frequency of women who smoked until the end of the pregnancy was not significantly reduced by the intervention. IMPLICATIONS: No implementation trials of smoking cessation interventions for pregnant women have been carried out in Latin American or in middle-income countries where health care systems or capacities may differ. We evaluated a multifaceted strategy designed to increase the frequency of pregnant women who receive brief smoking cessation counseling based on the 5As in Argentina and Uruguay. We found that the intervention showed a moderate effect in increasing the proportion of women receiving the 5As, with a third of women receiving counseling in more than one visit. However, the frequency of women who smoked until the end of the pregnancy was not significantly reduced by the intervention.

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial.

BACKGROUND: Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. METHODS: In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. FINDINGS: The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47,394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50,743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48,219 women in the intervention group and 867 (2%) of 51,523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). INTERPRETATION: Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Interest of pregnant women in the use of SMS (short message service) text messages for the improvement of perinatal and postnatal care.

BACKGROUND: Mobile health (mHealth) is emerging as a useful tool to improve healthcare access especially in the developing world, where limited access to health services is linked to poor antenatal care, and maternal and perinatal mortality.The objective of this study is to 1) understand pregnant women's access and usage of cell phones and 2) survey the health information needs and interests in a population attending public hospitals and health centers of two cities in Argentina. This information is not available and it is the basis to develop a strategy for improving maternal care via cell phones. METHODS: Questionnaires were verbally administered to pregnant women who were attending an antenatal care visit in community health centers and public hospitals in Rosario, Santa Fe and Mercedes, Corrientes. Participants were 18 years of age or older and had previously given birth. The data obtained was qualitative and analyzed using SPSS version 18. RESULTS: A total of 147 pregnant women meeting inclusion criteria (Rosario: 63; Mercedes: 84) were approached and verbally consented to participate. The average age was 29.5 years, most lived in urban areas (89%) with a mean travel time of 43.4 minutes required to get to the health center and 57.3 minutes to get the hospital.Ninety-six percent of women (n = 140) responded that they would like to receive text messages and cell phone calls with information regarding prenatal care, although the topics and period of time to receive information varied greatly. CONCLUSIONS: Considering the vast majority of the interviewed women had access to and were interested in receiving text messages and calls with educational information regarding pregnancy and infant health, pregnant women in Argentina could benefit from such an mHealth program. The low access to Internet suggests it is not an option for this population; however, this cannot be assumed as representative of the country's situation.To retain active participation, other forms of health communication, such as a 2-way text message systems or toll-free numbers, could be considered in the future. Cost of use and implementing these options should be studied.