RAPIDIRON Trial follow-up study - the RAPIDIRON-KIDS Study: protocol of a prospective observational follow-up study.

BACKGROUND: Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India's National Family Health Survey (NFHS-5) for 2019-2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019-21, India Fact Sheet). In 2021, the parent RAPIDIRON Trial (Derman et al., Trials 22:649, 2021) was initiated in two states in India, with the goal of assessing whether a dose of intravenous (IV) iron given to anemic women during early pregnancy results in a greater proportion of participants with normal hemoglobin concentrations in the third trimester and a lower proportion of participants with LBW deliveries compared to oral iron. As a follow-up to the RAPIDIRON Trial, the RAPIDIRON-KIDS Study will follow the offspring of previously randomized mothers to assess, neurobehavioral, hematological, and health outcomes. METHODS: This prospective observational cohort study will follow a subset of participants previously randomized as part of the RAPIDIRON Trial and their newborns. Study visits occur at birth, 6 weeks, 4 months, 12 months, 24 months, and 36 months and include blood sample collection with both maternal and infant participants and specific neurobehavioral assessments conducted with the infants (depending on the study visit). The primary outcomes of interest are (1) infant iron status as indicated by both hemoglobin and ferritin (a) at birth and (b) at 4 months of age and (2) the developmental quotient (DQ) for the cognitive domain of the Bayley Scales of Infant Development Version IV (BSID-IV) at 24 months of age. DISCUSSION: This RAPIDIRON-KIDS Study builds upon its parent RAPIDIRON Trial by following a subset of the previously randomized participants and their offspring through the first 3 years of life to assess neurodevelopmental and neurobehavioral (infants, children), hematological, and health outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05504863 , Registered on 17 August 2022. Clinical Trials Registry - India CTRI/2022/05/042933 . Registered on 31 May 2022.

RAPIDIRON: Reducing Anaemia in Pregnancy in India-a 3-arm, randomized-controlled trial comparing the effectiveness of oral iron with single-dose intravenous iron in the treatment of iron deficiency anaemia in pregnant women and reducing low birth weight deliveries.

BACKGROUND: Anaemia is a worldwide problem and iron deficiency is the most common cause. In pregnancy, anaemia increases the risk of adverse maternal, foetal and neonatal outcomes. India's anaemia rate is among the highest in the world with India's National Family Health Survey indicating over 50% of pregnant women were affected by anaemia. India's Anaemia Mukt Bharat-Intensified National Iron Plus Initiative aims to reduce the prevalence of anaemia among reproductive-age women, adolescents and children by 3% per year and facilitate the achievement of a Global World Health Assembly 2025 objective to achieve a 50% reduction of anaemia among women of reproductive age. However, preliminary results of the NFHS-5 survey completed in 2020 indicate that anaemia rates are increasing in some states and these targets are unlikely to be achieved. With oral iron being the first-line treatment for iron deficiency anaemia (IDA) in pregnancy, these results are likely to be impacted by the side effects, poor adherence to tablet ingestion and low therapeutic impact of oral iron. These reports suggest a new approach to treating IDA, specifically the importance of single-dose intravenous iron infusions, may be the key to India effectively reaching its targets for anaemia reduction. METHODS: This 3-arm, randomized controlled trial is powered to report two primary outcomes. The first is to assess whether a single dose of two different intravenous formulations administered early in the second trimester of pregnancy to women with moderate IDA will result in a higher percentage of participants achieving a normal for pregnancy Hb concentration at 30-34 weeks' gestation or just prior to delivery when compared to participants taking standard doses of oral iron. The second is a clinical outcome of low birth weight (LBW) (< 2500 g), with a hypothesis that the risk of LBW delivery will be lower in the intravenous iron arms when compared to the oral iron arm. DISCUSSION: The RAPIDIRON trial will provide evidence to determine if a single-dose intravenous iron infusion is more effective and economically feasible in reducing IDA in pregnancy than the current standard of care. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2020/09/027730. Registered on 10 September 2020, http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=46801&EncHid=&userName=anemia%20in%20pregnancy.

Early identification of preterm neonates at birth with a Tablet App for the Simplified Gestational Age Score (T-SGAS) when ultrasound gestational age dating is unavailable: A validation study.

BACKGROUND: In low resource settings recall of the date of the mother's last menstrual period may be unreliable and due to limited availability of prenatal ultrasound, gestational age of newborns may not be assessed reliably. Preterm babies are at high risk of morbidity and mortality so an alternative strategy is to identify them soon after birth is needed for early referral and management. OBJECTIVE: The objective of this study was to assess the accuracy in assessing prematurity of newborn, over and above birthweight, using a pictorial Simplified Gestational Age Score adapted for use as a Tablet App. METHODS: Two trained nurse midwives, blinded to each other's assessment and the actual gestational age of the baby used the app to assess gestational age at birth in 3 hospitals based on the following 4 parameters-newborn's posture, skin texture, breast and genital development. Inter-observer variation was evaluated and the optimal scoring cut-off to detect preterm birth was determined. Sensitivity and specificity of gestational age score using the tablet was estimated using combinations of last menstrual period and ultrasound as reference standards to assess preterm birth. The predictive accuracy of the score using the area under a receiver operating characteristic curve was also determined. To account for potential reference standard bias, we also evaluated the score using latent class models. RESULTS: A total of 8,591 live singleton births whose gestational age by last menstrual period and ultrasound was within 1 weeks of each other were enrolled. There was strong agreement between assessors (concordance correlation coefficient 0.77 (95% CI 0.76-0.78) and Fleiss' kappa was 0.76 (95% CI 0.76-0.78). The optimal cut-off for the score to predict preterm was 13. Irrespective of the reference standard, the specificity of the score was 90% and sensitivity varied from 40-50% and the predictive accuracy between 74%-79% for the reference standards. The likelihood ratio of a positive score varied between 3.75-4.88 while the same for a negative likelihood ratio consistently varied between 0.57-0.72. Latent class models showed similar results indicating no reference standard bias. CONCLUSION: Gestational age scores had strong inter-observer agreement, robust prediction of preterm births simplicity of use by nurse midwives and can be a useful tool in resource-limited scenarios. TRIAL REGISTRATION: The Tablet App for the Simplified Gestational Age Score (T-SGAS) study was registered at ClinicalTrials.gov NCT02408783.

Effect of Stellate Ganglion Block Treatment on Posttraumatic Stress Disorder Symptoms: A Randomized Clinical Trial.

Importance: This is the first multisite, randomized clinical trial of stellate ganglion block (SGB) outcomes on posttraumatic stress disorder (PTSD) symptoms. Objective: To determine whether paired SGB treatments at 0 and 2 weeks would result in improvement in mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity scores from baseline to 8 weeks. Design, Setting, and Participants: This multisite, blinded, sham-procedure, randomized clinical trial used a 2:1 SGB:sham ratio and was conducted from May 2016 through March 2018 in 3 US Army Interdisciplinary Pain Management Centers. Only physicians performing the procedures and the procedure nurses were aware of the intervention (but not the participants or assessors); their interactions with the participants were scripted and limited to the 2 interventions. Active-duty service members on stable psychotropic medication dosages who had a PTSD Checklist-Civilian Version (PCL-C) score of 32 or more at screening were included. Key exclusion criteria included a prior SGB treatment, selected psychiatric disorders or substance use disorders, moderate or severe traumatic brain injury, or suicidal ideation in the prior 2 months. Interventions: Paired right-sided SGB or sham procedures at weeks 0 and 2. Main Outcomes and Measures: Improvement of 10 or more points on mean CAPS-5 total symptom severity scores from baseline to 8 weeks, adjusted for site and baseline total symptom severity scores (planned a priori). Results: Of 190 screened individuals, 113 (59.5%; 100 male and 13 female participants; mean [SD] age, 37.3 [6.7] years) were eligible and randomized (74 to SGB and 39 to sham treatment), and 108 (95.6% of 113) completed the study. Baseline characteristics were similar in the SGB and sham treatment groups, with mean (SD) CAPS-5 scores of 37.6 (11.2) and 39.8 (14.4), respectively (on a scale of 0-80); 91 (80.0%) met CAPS-5 PTSD criteria. In an intent-to-treat analysis, adjusted mean total symptom severity score change was -12.6 points (95% CI, -15.5 to -9.7 points) for the group receiving SGB treatments, compared with -6.1 points (95% CI, -9.8 to -2.3 points) for those receiving sham treatment (P = .01). Conclusions and Relevance: In this trial of active-duty service members with PTSD symptoms (at a clinical threshold and subthreshold), 2 SGB treatments 2 weeks apart were effective in reducing CAPS-5 total symptom severity scores over 8 weeks. The mild-moderate baseline level of PTSD symptom severity and short follow-up time limit the generalizability of these findings, but the study suggests that SGB merits further trials as a PTSD treatment adjunct. Trial Registration: ClinicalTrials.gov identifier: NCT03077919.

Effect of Vaginal Mesh Hysteropexy vs Vaginal Hysterectomy With Uterosacral Ligament Suspension on Treatment Failure in Women With Uterovaginal Prolapse: A Randomized Clinical Trial.

Importance: Vaginal hysterectomy with suture apical suspension is commonly performed for uterovaginal prolapse. Transvaginal mesh hysteropexy is an alternative option. Objective: To compare the efficacy and adverse events of vaginal hysterectomy with suture apical suspension and transvaginal mesh hysteropexy. Design, Setting, Participants: At 9 clinical sites in the US Pelvic Floor Disorders Network, 183 postmenopausal women with symptomatic uterovaginal prolapse were enrolled in a randomized superiority clinical trial between April 2013 and February 2015. The study was designed for primary analysis when the last randomized participant reached 3 years of follow-up in February 2018. Interventions: Ninety-three women were randomized to undergo vaginal mesh hysteropexy and 90 were randomized to undergo vaginal hysterectomy with uterosacral ligament suspension. Main Outcomes and Measures: The primary treatment failure composite outcome (re-treatment of prolapse, prolapse beyond the hymen, or prolapse symptoms) was evaluated with survival models. Secondary outcomes included operative outcomes and adverse events, and were evaluated with longitudinal models or contingency tables as appropriate. Results: A total of 183 participants (mean age, 66 years) were randomized, 175 were included in the trial, and 169 (97%) completed the 3-year follow-up. The primary outcome was not significantly different among women who underwent hysteropexy vs hysterectomy through 48 months (adjusted hazard ratio, 0.62 [95% CI, 0.38-1.02]; P = .06; 36-month adjusted failure incidence, 26% vs 38%). Mean (SD) operative time was lower in the hysteropexy group vs the hysterectomy group (111.5 [39.7] min vs 156.7 [43.9] min; difference, -45.2 [95% CI, -57.7 to -32.7]; P = <.001). Adverse events in the hysteropexy vs hysterectomy groups included mesh exposure (8% vs 0%), ureteral kinking managed intraoperatively (0% vs 7%), granulation tissue after 12 weeks (1% vs 11%), and suture exposure after 12 weeks (3% vs 21%). Conclusions and Relevance: Among women with symptomatic uterovaginal prolapse undergoing vaginal surgery, vaginal mesh hysteropexy compared with vaginal hysterectomy with uterosacral ligament suspension did not result in a significantly lower rate of the composite prolapse outcome after 3 years. However, imprecision in study results precludes a definitive conclusion, and further research is needed to assess whether vaginal mesh hysteropexy is more effective than vaginal hysterectomy with uterosacral ligament suspension. Trial Registration: ClinicalTrials.gov Identifier: NCT01802281.

Polyhydramnios among women in a cluster-randomized trial of ultrasound during prenatal care within five low and low-middle income countries: a secondary analysis of the first look study.

BACKGROUND: In many low and low-middle income countries, the incidence of polyhydramnios is unknown, in part because ultrasound technology is not routinely used. Our objective was to report the incidence of polyhydramnios in five low and low-middle income countries, to determine maternal characteristics associated with polyhydramnios, and report pregnancy and neonatal outcomes. METHODS: We performed a secondary analysis of the First Look Study, a multi-national, cluster-randomized trial of ultrasound during prenatal care. We evaluated all women enrolled from Guatemala, Pakistan, Zambia, Kenya and the Democratic Republic of Congo (DRC) who received an examination by prenatal ultrasound. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models with general estimating equations to control for cluster-level effects. The diagnosis of polyhydramnios was confrimed by an U.S. based radiologist in a majority of cases (62%). RESULTS: We identified 305/18,640 (1.6%) cases of polyhydramnios. 229 (75%) cases were from the DRC, with an incidence of 10%. A higher percentage of women with polyhydramnios experienced obstructed labor (7% vs 4%) and fetal malposition (4% vs 2%). Neonatal death was more common when polyhydramnios was present (OR 2.43; CI 1.15, 5.13). CONCLUSIONS: Polyhydramnios occured in these low and low-middle income countries at a rate similar to high-income contries except in the DRC where the incidence was 10%. Polyhydramnios was associated with obstructed labor, fetal malposition, and neonatal death. TRIAL REGISTRATION: NCT01990625 , November 21, 2013.

Early Identification of Preterm Neonates at Birth With a Tablet App for the Simplified Gestational Age Score (T-SGAS) When Ultrasound Gestational Age Dating Is Unavailable: Protocol for a Validation Study.

BACKGROUND: Although rates of preterm birth continue to increase globally, identification of preterm from low birth weight infants remains a challenge. The burden of low birth weight vs preterm is greatest in resource-limited settings, where gestational age (GA) prior to delivery is frequently not known because ultrasound in early pregnancy is not available and estimates of the date of the mother's last menstrual period (LMP) may not be reliable. An alternative option is to assess GA at birth to optimize referral and care of preterm newborns. We previously developed and pilot-tested a system to measure the simplified gestational age score (SGAS) based on 4 easily observable neonatal characteristics. OBJECTIVE: The objective of this study is to adapt the scoring system as a tablet app (potentially scalable approach) to assess feasibility of use and to validate whether the scoring system accurately predicts prematurity by itself, over and above birth weight in a large sample of newborns. METHODS: The study is based in Nagpur, India, at the Research Unit of the National Institute of Child Health and Human Development's Global Network for Women's and Children's Health Research. The Android tablet app for the SGAS (T-SGAS) displays de-identified photographs of skin, breasts, and genitalia across a range of GAs and line drawings of infant posture. Each item is associated with a score. The user is trained to choose the photograph or line drawing that most closely matches the newborn being evaluated, and the app determines the neonate's GA category (preterm or term) from the cumulative score. The validation study will be conducted in 3 second level care facilities (most deliveries in India occur in hospitals, and women known to be at risk of preterm birth are referred to second level care facilities). Within 24 hours of delivery, women and their babies who are stable will be enrolled in the study. Two auxiliary nurse midwives (ANMs) blinded to prior GA assessments will use the T-SGAS to estimate the GA status of the newborn. An independent data collector will abstract the GA from the ultrasound recorded in the hospital chart and record the date of the mother's LMP. Eligibility for analysis is determined by the ultrasound and LMP data being collected within 1 week of each other to have a rigorous assessment of true GA. RESULTS: Publication of the results of the study is anticipated in 2019. CONCLUSIONS: Until GA dating by ultrasound is universally available and easy to use in resource-limited settings, and where there are restrictions on ultrasound use due to their use for sex determination and abortion of female fetuses, this study will determine whether the T-SGAS app can accurately assess GA in risk categories at birth. TRIAL REGISTRATION: ClinicalTrials.gov NCT02408783; https://clinicaltrials.gov/ct2/show/NCT02408783 (Archived by Webcite at http://www.webcitation.org/75S2kmr3T). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11913.

Association between birth attendant type and delivery site and perinatal outcomes.

OBJECTIVE: To test the hypothesis that modified perinatal mortality, early neonatal mortality, and other measures of perinatal mortality are lower with facility births than with home births among deliveries conducted by traditional birth attendants (TBAs) or nurse-midwives. METHOD: This population-based observational study used data collected prospectively for home and facility deliveries conducted by TBAs and nurse-midwives in 13 rural communities in Zambia between September 1, 2009, and December 31, 2015. RESULTS: We enrolled 48 956 pregnant women. In adjusted analysis, modified perinatal mortality (adjusted odds ratio [aOR] 0.63, 95% confidence interval [CI] 0.45-0.88), early neonatal mortality (0.48, 0.33-0.69), and fresh stillbirth/day-1 neonatal mortality (0.55, 0.38-0.80) were lower among home deliveries than among facility deliveries conducted by TBAs, but did not differ among deliveries conducted by nurse-midwives. Rates of fresh stillbirth did not differ between home and facility delivery by either TBAs (aOR 1.03, 95% CI 0.64-1.66) or nurse-midwives (1.19, 0.67-2.10). CONCLUSION: Our findings show significant reductions in modified perinatal mortality, early neonatal mortality, and fresh stillbirth/day-1 neonatal mortality among home deliveries done by TBAs. This may be explained by robust community structures built by our program and referral bias of complicated cases.

Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm.

BACKGROUND: Low birth weight in term-born individuals correlates with adverse cardiometabolic outcomes; excess glucocorticoid exposure has been linked to these relationships. We hypothesized that cortisol and adrenal androgens would correlate inversely with birthweight and directly with markers of cardiometabolic risk in school-aged children born extremely preterm; further, preterm-born would have increased cortisol and adrenal androgens compared to term-born children. METHODS: Saliva samples were obtained at age 6 from 219 preterm-born children followed since birth and 40 term-born children and analyzed for dehydroepiandrosterone (DHEA) and cortisol. Cortisol was also measured at home (awakening, 30' later, evening). RESULTS: For preterm-born children, cortisol and DHEA correlated inversely with weight and length Z-scores at 36 weeks PMA and positively with systolic BP. DHEA was higher in preterm-born than term-born children (boys p < 0.01; girls p = 0.04). Cortisol was similar between preterm-born and term-born at study visit; however, preterm-born children showed a blunted morning cortisol. In term-born children, DHEA correlated with BMI (p = 0.04), subscapular, and abdominal skinfold thicknesses (both p < 0.01). CONCLUSION: Cortisol and DHEA correlated inversely with early postnatal growth and directly with systolic BP in extremely preterm-born children, suggesting perinatal programming. Blunted morning cortisol may reflect NICU stress, as seen after other adverse childhood experiences (ACEs).

Concomitant Anterior Repair, Preoperative Prolapse Severity, and Anatomic Prolapse Outcomes After Vaginal Apical Procedures.

OBJECTIVE: The aim of the study was to compare anterior and overall prolapse prevalence at 1 year in surgical participants with or without concomitant anterior repair (AR) at the time of sacrospinous ligament fixation (SSLF) or uterosacral ligament suspension (ULS). METHODS: This is a secondary analysis of two surgical trials; concomitant AR was performed at surgeon's discretion. Anterior anatomic success was defined as pelvic organ prolapse quantification of prolapse point Ba ≤0 and overall success was defined as pelvic organ prolapse quantification points Ba, Bp, and C ≤0 at 12 months. RESULTS: Sixty-three percent (441/701) of the participants underwent concomitant AR and were older, more often postmenopausal, had previous hysterectomy, and had higher-stage anterior, but not apical prolapse. Anterior anatomic success was marginally but statistically better in the combined group (SSLF and ULS) with concomitant AR (82% vs 80%, P = 0.03). In subanalyses, the improvement in anatomic support with AR was observed only in the SSLF subgroup (81% vs 73%, P = 0.02) and mostly in the SSLF subgroup with higher preoperative stage (74% vs 57%, P = 0.02). Anterior repair did not improve success rates in participants with lower-stage prolapse or undergoing ULS. Overall success rates were similar to anterior anatomic success rates. Participants with higher-stage preoperative anterior prolapse had significantly lower success rates. CONCLUSIONS: In the absence of clinical trial data, this analysis suggests an AR should be considered for women with higher-stage prolapse undergoing an SSLF. Preoperative prolapse severity is a strong predictor of poor anatomic outcomes with native tissue vaginal apical surgeries.

A Prospective, Population-Based Study of Trends in Operative Vaginal Delivery Compared to Cesarean Delivery Rates in Low- and Middle-Income Countries, 2010-2016.

OBJECTIVE: Few data are available on cesarean delivery and operative vaginal delivery trends in low- and middle-income countries. Our objective was to analyze a prospective population-based registry including eight sites in seven low- and middle-income countries to observe trends in operative vaginal delivery versus cesarean delivery rates over time, across sites. STUDY DESIGN: A prospective population-based study, including home and facility births among women enrolled from 2010 to 2016, was performed in communities in Argentina, Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia. Women were enrolled during pregnancy and delivery outcome data were collected. RESULTS: We analyzed 354,287 women; 4,119 (1.2%) underwent an operative vaginal delivery and 45,032 (11.2%) delivered by cesarean. Across all sites with data for 7 years, rates of operative vaginal delivery decreased from 1.6 to 0.3%, while cesarean delivery increased from 6.4 to 14.4%. Similar trends were seen when individual country data were analyzed. Operative vaginal delivery rates decreased in both hospitals and clinics, except in the hospital setting at one of the Indian sites. CONCLUSION: In low- and middle-income countries, operative vaginal delivery is becoming less utilized while cesarean delivery is becoming an increasingly common mode of delivery.

Malpresentation in low- and middle-income countries: Associations with perinatal and maternal outcomes in the Global Network.

INTRODUCTION: Uncertainty exists regarding the impact of malpresentation on pregnancy outcomes and the optimal mode of delivery in low- and middle-income countries. We sought to compare outcomes between cephalic and non-cephalic pregnancies. MATERIAL AND METHODS: Using the NICHD Global Network's prospective, population-based registry of pregnancy outcomes from 2010 to 2016, we studied outcomes in 436 112 singleton pregnancies. Robust Poisson regressions were used to estimate the risk of adverse outcomes associated with malpresentation. We examined rates of cesarean delivery for malpresentation and compared outcomes between cesarean and vaginal delivery by region. RESULTS: Across all regions, stillbirth and neonatal mortality rates were higher among deliveries with malpresentation. In adjusted analysis, malpresentation was significantly associated with stillbirth (adjusted relative risk [aRR] 4.0, 95% confidence interval [CI] 3.7-4.5) and neonatal mortality (aRR 2.3, 95% CI 2.1-2.6). Women with deliveries complicated by malpresentation had higher rates of morbidity and mortality. Rates of cesarean delivery for malpresentation ranged from 27% to 87% among regions. Compared with cesarean delivery, vaginal delivery for malpresentation was associated with increased maternal risk, especially postpartum hemorrhage (aRR 5.0, 95% CI; 3.6-7.1). CONCLUSIONS: In a cohort of deliveries in low- and middle-income countries, malpresentation was associated with increased perinatal and maternal risk. Further research is needed to determine the best management of these pregnancies.

Monitoring of birth registry coverage and data quality utilizing lot quality assurance sampling methodology: A pilot study.

BACKGROUND: Effectively monitoring the coverage and quality of data in low-resource settings is challenging. Lot quality assurance sampling (LQAS) is a method to classify coverage as adequate or inadequate. The aim of this pilot study is sought to determine the coverage and quality of a birth registry in a rural district in Pakistan. METHODS: This survey was conducted in 14 clusters of Thatta, Pakistan. LQAS methodology was used to monitor the birth registry from December 2015 to February 2016. We randomly selected 19 villages from each cluster. We used a short questionnaire to review the quality of data collection for select variables. Frequency and percentages were reported for categorical variables. For data validation, Kappa statistics (κ) were applied to assess the agreement between categorical observations, and the Bland-Altman test was used to assess agreement for continuous data. RESULTS: Of the 14 clusters sampled, 12 clusters had adequate coverage. Agreement of hemoglobin performance between the women's response and information in birth registry data was good (κ = 0.718) (95% confidence interval [CI]: 0.58-0.82); agreement on birth outcome recorded by the workers in the registry and as mentioned by women was very good (κ = 1.0); and agreement whether birth weight was assessed within 48 h of delivery was good (κ = 0.648) (0.37-0.92). CONCLUSION: LQAS is a powerful tool to monitor coverage and data quality of the birth registry maintained by the global network for women's and children's health in Pakistan and potentially for data from other surveillance systems.

Early pregnancy loss in Belagavi, Karnataka, India 2014-2017: a prospective population-based observational study in a low-resource setting.

BACKGROUND: The prevalence of early pregnancy loss through miscarriage and medically terminated pregnancy (MTP) is largely unknown due to lack of early registration of pregnancies in most regions, and especially in low- and middle-income countries. Understanding the rates of early pregnancy loss as well as the characteristics of pregnant women who experience miscarriage or MTP can assist in better planning of reproductive health needs of women. METHODS: A prospective, population-based study was conducted in Belagavi District, south India. Using an active surveillance system of women of childbearing age, all women were enrolled as soon as possible during pregnancy. We evaluated rates and risk factors of miscarriage and MTP between 6 and 20 weeks gestation as well as rates of stillbirth and neonatal death. A hypothetical cohort of 1000 women pregnant at 6 weeks was created to demonstrate the impact of miscarriage and MTP on pregnancy outcome. RESULTS: A total of 30,166 women enrolled from 2014 to 2017 were included in this analysis. The rate of miscarriage per 1000 ongoing pregnancies between 6 and 8 weeks was 115.3, between 8 and 12 weeks the miscarriage rate was 101.9 per 1000 ongoing pregnancies and between 12 and 20 weeks the miscarriage rate was 60.3 per 1000 ongoing pregnancies. For those periods, the MTP rate was 40.2, 45.4, and 48.3 per 1000 ongoing pregnancies respectively. The stillbirth rate was 26/1000 and the neonatal mortality rate was 24/1000. The majority of miscarriages (96.6%) were unattended and occurred at home. The majority of MTPs occurred in a hospital and with a physician in attendance (69.6%), while 20.7% of MTPs occurred outside a health facility. Women who experienced a miscarriage were older and had a higher level of education but were less likely to be anemic than those with an ongoing pregnancy at 20 weeks. Women with MTP were older, had a higher level of education, higher parity, and higher BMI, compared to those with an ongoing pregnancy, but these results were not consistent across gestational age periods. CONCLUSIONS: Of women with an ongoing pregnancy at 6 weeks, about 60% will have a living infant at 28 days of age. Two thirds of the losses will be spontaneous miscarriages and one third will be secondary to a MTP. High maternal age and education were the risk factors associated with miscarriage and MTP. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475 .

Trends and determinants of stillbirth in developing countries: results from the Global Network's Population-Based Birth Registry.

BACKGROUND: Stillbirth rates remain high, especially in low and middle-income countries, where rates are 25 per 1000, ten-fold higher than in high-income countries. The United Nations' Every Newborn Action Plan has set a goal of 12 stillbirths per 1000 births by 2030 for all countries. METHODS: From a population-based pregnancy outcome registry, including data from 2010 to 2016 from two sites each in Africa (Zambia and Kenya) and India (Nagpur and Belagavi), as well as sites in Pakistan and Guatemala, we evaluated the stillbirth rates and rates of annual decline as well as risk factors for 427,111 births of which 12,181 were stillbirths. RESULTS: The mean stillbirth rates for the sites were 21.3 per 1000 births for Africa, 25.3 per 1000 births for India, 56.9 per 1000 births for Pakistan and 19.9 per 1000 births for Guatemala. From 2010 to 2016, across all sites, the mean stillbirth rate declined from 31.7 per 1000 births to 26.4 per 1000 births for an average annual decline of 3.0%. Risk factors for stillbirth were similar across the sites and included maternal age < 20 years and age > 35 years. Compared to parity 1-2, zero parity and parity > 3 were both associated with increased stillbirth risk and compared to women with any prenatal care, women with no prenatal care had significantly increased risk of stillbirth in all sites. CONCLUSIONS: At the current rates of decline, stillbirth rates in these sites will not reach the Every Newborn Action Plan goal of 12 per 1000 births by 2030. More attention to the risk factors and treating the causes of stillbirths will be required to reach the Every Newborn Action Plan goal of stillbirth reduction. TRIAL REGISTRATION: NCT01073475 .

Open sacrocolpopexy and vaginal apical repair: retrospective comparison of success and serious complications.

INTRODUCTION AND HYPOTHESIS: We compared treatment success and adverse events between women undergoing open abdominal sacrocolpopexy (ASC) vs vaginal repair (VAR) using data from women enrolled in one of three multicenter trials. We hypothesized that ASC would result in better outcomes than VAR. METHODS: Participants underwent apical repair of stage 2-4 prolapse. Vaginal repair included uterosacral, sacrospinous, and iliococcygeal suspensions; sacrocolpopexies were via laparotomy. Success was defined as no bothersome bulge symptoms, no prolapse beyond the hymen, and no retreatment up to 24 months. Adverse events were collected at multiple time points. Outcomes were analyzed using longitudinal mixed-effects models to obtain valid outcome estimates at specific visit times, accounting for data missing at random. Comparisons were controlled for center, age, body mass index (BMI), initial Pelvic Organ Prolapse Quantification (POP-Q) stage, baseline scores, prior prolapse repair, and concurrent repairs. RESULTS: Of women who met inclusion criteria (1022 of 1159 eligibile), 701 underwent vaginal repair. The ASC group (n = 321) was older, more likely white, had prior prolapse repairs, and stage 4 prolapse (all p < 0.05). While POP-Q measurements and symptoms improved in both groups, treatment success was higher in the ASC group [odds ratio (OR) 6.00, 95% confidence interval (CI) 3.45-10.44). The groups did not differ significantly in most questionnaire responses at 12 months and overall improvement in bowel and bladder function. By 24 months, fewer patients had undergone retreatment (2% ASC vs 5% VAR); serious adverse events did not differ significantly through 6 weeks (13% vs 5%, OR 2.0, 95% CI 0.9-4.7), and 12 months (26% vs 13%, OR 1.6, 95% CI 0.9-2.9), respectively. CONCLUSIONS: Open sacrocolpopexy resulted in more successful prolapse treatment at 2 years.

Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial.

BACKGROUND: Urgency urinary incontinence (UUI) is a chronic condition for which sacral neuromodulation (SNM) (InterStim/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/Allergan) are utilized. These therapies have not been compared over extended time. OBJECTIVE: To compare UUI episodes (UUIE) over 24 mo following SNM or BTX. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized, extension trial (February 2012-July 2016) at nine US medical centers involving 386 women with ≥6 UUIE over 3 d inadequately managed by medications. Participants were clinical responders to treatment: ≥50% reduction in UUIEs after SNM placement or 1 mo post BTX. INTERVENTION: SNM (n=194) versus 200 U BTX (n=192). SNM reprogrammings occurred throughout the 24 mo. After 6 mo, two additional BTX injections were allowed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome: change in mean daily UUIE over 24 mo. SECONDARY OUTCOMES: no UUIE, ≥75% and ≥50% UUIE reduction; Overactive Bladder Questionnaire Short Form; Urinary Distress Inventory short form; Incontinence Impact Questionnaire; Patient Global Impression of Improvement; Overactive Bladder Satisfaction of Treatment Questionnaire; and adverse events (AEs). Primary analysis used a linear mixed model. RESULTS AND LIMITATIONS: Outcome data were available for 260/298 (87%) clinical responders. No difference in decreased mean UUIE was found over 24 mo (-3.88 vs -3.50 episodes/d,95% confidence interval [CI]=-0.14-0.89; p=0.15), with no differences in UUI resolution, ≥75% or ≥50% UUIE reduction. BTX group maintained higher satisfaction (mean difference=-9.14, 95% CI=-14.38--3.90; p<0.001), treatment endorsement (mean difference=-12.16, 95% CI=-17.7--6.63; p<0.001) through 24 mo. Other secondary measures did not differ. Recurrent urinary tract infections (UTIs) were higher after BTX (24% vs 10%; p<0.01), 6% required intermittent catheterization post second injection. SNM revision and removals occurred in 3% and 9% patients, respectively. CONCLUSIONS: Both treatments offered sustainable UUI improvement, and higher BTX dosing had low clean intermittent catheterization rates, but with UTI risk. SNM revision/removal rates were low due to standardized lead placement with strict treatment response definitions. PATIENT SUMMARY: We compared a large group of US women with severe urgency urinary incontinence (UUI) who received sacral neuromodulation (InterStim) or onabotulinumtoxinA (Botox A) therapy during a 2-yr period. We found that both therapies had similar success in reducing UUI symptoms, and adverse events were low. However, women in the BotoxA group had higher satisfaction and endorsement with their treatment, but with a higher chance of a urinary tract infection. We conclude that both therapies offer sustained reduction in daily incontinence over 2 yr.

Surgical Outcomes After Apical Repair for Vault Compared With Uterovaginal Prolapse.

OBJECTIVE: To retrospectively compare surgical success and complications between vaginal vault prolapse compared with uterovaginal prolapse in women who underwent apical prolapse repair for stage II-IV prolapse. METHODS: Women in one of three Pelvic Floor Disorders Network prolapse surgical trials were included. Absence of bothersome bulge symptoms, no prolapse beyond the hymen, and no subsequent prolapse treatment defined success and was our primary outcome. Secondary outcomes included comparison of quality-of-life measures, anatomic changes, and adverse events. Pelvic organ prolapse quantification (POP-Q) and quality-of-life measures were administered at baseline and 1-2 years postoperatively. Comparisons were controlled for study site, age, body mass index, baseline POP-Q, apical and anterior or posterior repair performed, and prior prolapse repair. Outcomes measured at multiple time points were analyzed using longitudinal models to assess whether differences existed across study follow-up. RESULTS: Four hundred twenty-one women underwent vault prolapse, and 601 underwent uterovaginal prolapse apical repair. The vault prolapse group was older, more likely to be white, and to have prior urinary incontinence or prolapse repair, stage IV prolapse, and more prolapse bother on a validated scale (all P≤.034). The vault prolapse group was more likely to undergo sacrocolpopexy (228/421 [54%] vs 93/601 [15%]); the uterovaginal prolapse group was more likely to undergo vaginal repair (508/601 [85%] vs 193/421 [46%] P<.001). There were no differences in success (odds ratio [OR] 0.76 for vault prolapse vs uterovaginal prolapse, 95% CI 0.51-1.15, P=.20), changes in Pelvic Organ Prolapse Distress Inventory scores (-79.4 vs -79.8, P=.89), postoperative POP-Q point C measurements (-7.0 vs -7.1 cm, P=.41), or serious adverse events (86/421 [20%] vs 90/601 [15%], P=.86) between groups. Among women who underwent a vaginal approach for repair of vault prolapse (n=193) or uterovaginal prolapse (n=508), there were no differences in success rates (OR 0.67, 95% CI 0.43-1.04, P=.09) at 1-2 years postoperatively. CONCLUSION: Surgical success of stage II-IV vault prolapse and uterovaginal prolapse apical repair was similar whether performed vaginally or abdominally at 1-2 years postoperatively.

Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.

BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score. RESULTS: In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group. CONCLUSIONS: Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials.gov number, NCT00114530 .).