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Item Evaluating the effect of care around labor and delivery practices on early neonatal mortality in the Global Network's Maternal and Newborn Health Registry(Springer Nature, 2020-11-30) Patel, Archana B.; Simmons, Elizabeth M.; Rao, Sowmya R.; Moore, Janet; Nolen, Tracy L.; Goldenberg, Robert L.; Goudar, Shivaprasad S.; Somannavar, Manjunath S.; Esamai, Fabian; Nyongesa, Paul; Garces, Ana L.; Chomba, Elwyn; Mwenechanya, Musaku; Saleem, Sarah; Naqvi, Farnaz; Bauserman, Melissa; Bucher, Sherri; Krebs, Nancy F.; Derman, Richard J.; Carlo, Waldemar A.; Koso‑ThomasMcClure, Marion Elizabeth M.; Hibberd, Patricia L.; Pediatrics, School of MedicineBackground: Neonatal deaths in first 28-days of life represent 47% of all deaths under the age of five years globally and are a focus of the United Nation's (UN's) Sustainable Development Goals. Pregnant women are delivering in facilities but that does not indicate quality of care during delivery and the postpartum period. The World Health Organization's Essential Newborn Care (ENC) package reduces neonatal mortality, but lacks a simple and valid composite index that measures its effectiveness. Methods: Data on 5 intra-partum and 3 post-partum practices (indicators) recommended as part of ENC, routinely collected in NICHD's Global Network's (GN) Maternal Newborn Health Registry (MNHR) between 2010 and 2013, were included. We evaluated if all 8 practices (Care around Delivery - CAD), combined as an index was associated with reduced early neonatal mortality rates (days 0-6 of life). Results: A total of 150,848 live births were included in the analysis. The individual indicators varied across sites. All components were present in 19.9% births (range 0.4 to 31% across sites). Present indicators (8 components) were associated with reduced early neonatal mortality [adjusted RR (95% CI):0.81 (0.77, 0.85); p < 0.0001]. Despite an overall association between CAD and early neonatal mortality (RR < 1.0 for all early mortality): delivery by skilled birth attendant; presence of fetal heart and delayed bathing were associated with increased early neonatal mortality. Conclusions: Present indicators (8 practices) of CAD were associated with a 19% reduction in the risk of neonatal death in the diverse health facilities where delivery occurred within the GN MNHR. These indicators could be monitored to identify facilities that need to improve compliance with ENC practices to reduce preventable neonatal deaths. Three of the 8 indicators were associated with increased neonatal mortality, due to baby being sick at birth. Although promising, this composite index needs refinement before use to monitor facility-based quality of care in association with early neonatal mortality.Item Impact of exposure to cooking fuels on stillbirths, perinatal, very early and late neonatal mortality - a multicenter prospective cohort study in rural communities in India, Pakistan, Kenya, Zambia and Guatemala(Springer (Biomed Central Ltd.), 2015) Patel, Archana B.; Meleth, Sreelatha; Pasha, Omrana; Goudar, Shivaprasad S.; Esamai, Fabian; Garces, Ana L.; Chomba, Elwyn; McClure, Elizabeth M.; Wright, Linda L.; Koso-Thomas, Marion; Moore, Janet L.; Saleem, Sarah; Liechty, Edward A.; Goldenberg, Robert L.; Derman, Richard J.; Hambidge, K. Michael; Carlo, Waldemar A.; Hibberd, Patricia L.; Department of Pediatrics, IU School of MedicineBACKGROUND: Consequences of exposure to household air pollution (HAP) from biomass fuels used for cooking on neonatal deaths and stillbirths is poorly understood. In a large multi-country observational study, we examined whether exposure to HAP was associated with perinatal mortality (stillbirths from gestation week 20 and deaths through day 7 of life) as well as when the deaths occurred (macerated, non-macerated stillbirths, very early neonatal mortality (day 0-2) and later neonatal mortality (day 3-28). Questions addressing household fuel use were asked at pregnancy, delivery, and neonatal follow-up visits in a prospective cohort study of pregnant women in rural communities in five low and lower middle income countries participating in the Global Network for Women and Children's Health's Maternal and Newborn Health Registry. The study was conducted between May 2011 and October 2012. Polluting fuels included kerosene, charcoal, coal, wood, straw, crop waste and dung. Clean fuels included electricity, liquefied petroleum gas (LPG), natural gas and biogas. RESULTS: We studied the outcomes of 65,912 singleton pregnancies, 18 % from households using clean fuels (59 % LPG) and 82 % from households using polluting fuels (86 % wood). Compared to households cooking with clean fuels, there was an increased risk of perinatal mortality among households using polluting fuels (adjusted relative risk (aRR) 1.44, 95 % confidence interval (CI) 1.30-1.61). Exposure to HAP increased the risk of having a macerated stillbirth (adjusted odds ratio (aOR) 1.66, 95%CI 1.23-2.25), non-macerated stillbirth (aOR 1.43, 95 % CI 1.15-1.85) and very early neonatal mortality (aOR 1.82, 95 % CI 1.47-2.22). CONCLUSIONS: Perinatal mortality was associated with exposure to HAP from week 20 of pregnancy through at least day 2 of life. Since pregnancy losses before labor and delivery are difficult to track, the effect of exposure to polluting fuels on global perinatal mortality may have previously been underestimated. TRIAL REGISTRATION: ClinicalTrials.gov NCT01073475.Item Maternal age extremes and adverse pregnancy outcomes in low-resourced settings(Frontiers Media, 2023-11-28) Nyongesa, Paul; Ekhaguere, Osayame A.; Marete, Irene; Tenge, Constance; Kemoi, Milsort; Bann, Carla M.; Bucher, Sherri L.; Patel, Archana B.; Hibberd, Patricia L.; Naqvi, Farnaz; Saleem, Sarah; Goldenberg, Robert L.; Goudar, Shivaprasad S.; Derman, Richard J.; Krebs, Nancy F.; Garces, Ana; Chomba, Elwyn; Carlo, Waldemar A.; Mwenechanya, Musaku; Lokangaka, Adrien; Tshefu, Antoinette K.; Bauserman, Melissa; Koso-Thomas, Marion; Moore, Janet L.; McClure, Elizabeth M.; Liechty, Edward A.; Esamai, Fabian; Pediatrics, School of MedicineIntroduction: Adolescent (<20 years) and advanced maternal age (>35 years) pregnancies carry adverse risks and warrant a critical review in low- and middle-income countries where the burden of adverse pregnancy outcomes is highest. Objective: To describe the prevalence and adverse pregnancy (maternal, perinatal, and neonatal) outcomes associated with extremes of maternal age across six countries. Patients and methods: We performed a historical cohort analysis on prospectively collected data from a population-based cohort study conducted in the Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia between 2010 and 2020. We included pregnant women and their neonates. We describe the prevalence and adverse pregnancy outcomes associated with pregnancies in these maternal age groups (<20, 20-24, 25-29, 30-35, and >35 years). Relative risks and 95% confidence intervals of each adverse pregnancy outcome comparing each maternal age group to the reference group of 20-24 years were obtained by fitting a Poisson model adjusting for site, maternal age, parity, multiple gestations, maternal education, antenatal care, and delivery location. Analysis by region was also performed. Results: We analyzed 602,884 deliveries; 13% (78,584) were adolescents, and 5% (28,677) were advanced maternal age (AMA). The overall maternal mortality ratio (MMR) was 147 deaths per 100,000 live births and increased with advancing maternal age: 83 in the adolescent and 298 in the AMA group. The AMA groups had the highest MMR in all regions. Adolescent pregnancy was associated with an adjusted relative risk (aRR) of 1.07 (1.02-1.11) for perinatal mortality and 1.13 (1.06-1.19) for neonatal mortality. In contrast, AMA was associated with an aRR of 2.55 (1.81 to 3.59) for maternal mortality, 1.58 (1.49-1.67) for perinatal mortality, and 1.30 (1.20-1.41) for neonatal mortality, compared to pregnancy in women 20-24 years. This pattern was overall similar in all regions, even in the <18 and 18-19 age groups. Conclusion: The maternal mortality ratio in the LMICs assessed is high and increased with advancing maternal age groups. While less prevalent, AMA was associated with a higher risk of adverse maternal mortality and, like adolescence, was associated with adverse perinatal mortality with little regional variation.Item Regional trends in birth weight in low- and middle-income countries 2013–2018(BMC, 2020-12-17) Marete, Irene; Ekhaguere, Osayame; Bann, Carla M.; Bucher, Sherri L.; Nyongesa, Paul; Patel, Archana B.; Hibberd, Patricia L.; Saleem, Sarah; Goldenberg, Robert L.; Goudar, Shivaprasad S.; Derman, Richard J.; Garces, Ana L.; Krebs, Nancy F.; Chomba, Elwyn; Carlo, Waldemar A.; Lokangaka, Adien; Bauserman, Melissa; Koso‑Thomas, Marion; Moore, Janet L.; McClure, Elizabeth M.; Esamai, Fabian; Pediatrics, School of MedicineBackground: Birth weight (BW) is a strong predictor of neonatal outcomes. The purpose of this study was to compare BWs between global regions (south Asia, sub-Saharan Africa, Central America) prospectively and to determine if trends exist in BW over time using the population-based maternal and newborn registry (MNHR) of the Global Network for Women'sand Children's Health Research (Global Network). Methods: The MNHR is a prospective observational population-based registryof six research sites participating in the Global Network (2013-2018), within five low- and middle-income countries (Kenya, Zambia, India, Pakistan, and Guatemala) in threeglobal regions (sub-Saharan Af rica, south Asia, Central America). The birth weights were obtained for all infants born during the study period. This was done either by abstracting from the infants' health facility records or from direct measurement by the registry staff for infants born at home. After controlling for demographic characteristics, mixed-effect regression models were utilized to examine regional differences in birth weights over time. Results: The overall BW meanswere higher for the African sites (Zambia and Kenya), 3186 g (SD 463 g) in 2013 and 3149 g (SD 449 g) in 2018, ascompared to Asian sites (Belagavi and Nagpur, India and Pakistan), 2717 g (SD450 g) in 2013 and 2713 g (SD 452 g) in 2018. The Central American site (Guatemala) had a mean BW intermediate between the African and south Asian sites, 2928 g (SD 452) in 2013, and 2874 g (SD 448) in 2018. The low birth weight (LBW) incidence was highest in the south Asian sites (India and Pakistan) and lowest in the African sites (Kenya and Zambia). The size of regional differences varied somewhat over time with slight decreases in the gap in birth weights between the African and Asian sites and slight increases in the gap between the African and Central American sites. Conclusions: Overall, BWmeans by global region did not change significantly over the 5-year study period. From 2013 to 2018, infants enrolled at the African sites demonstrated the highest BW means overall across the entire study period, particularly as compared to Asian sites. The incidence of LBW was highest in the Asian sites (India and Pakistan) compared to the African and Central American sites. Trial registration The study is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475.Item Stillbirth 2010-2018: a prospective, population-based, multi-country study from the Global Network(Springer Nature, 2020-11-30) McClure, Elizabeth M.; Saleem, Sarah; Goudar, Shivaprasad S.; Garces, Ana; Whitworth, Ryan; Esamai, Fabian; Patel, Archana B.; Sunder Tikmani, Shiyam; Mwenechanya, Musaku; Chomba, Elwyn; Lokangaka, Adrien; Bose, Carl L.; Bucher, Sherri; Liechty, Edward A.; Krebs, Nancy F.; Kumar, S. Yogesh; Derman, Richard J.; Hibberd, Patricia L.; Carlo, Waldemar A.; Moore, Janet L.; Nolen, Tracy L.; Koso-Thomas, Marion; Goldenberg, Robert L.; Pediatrics, School of MedicineBackground: Stillbirth rates are high and represent a substantial proportion of the under-5 mortality in low and middle-income countries (LMIC). In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented cause of stillbirths or the trends in rate of stillbirth over time. Methods: We undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, Democratic Republic of Congo, India, Pakistan, and Guatemala). Staff collected demographic and health care characteristics with outcomes obtained at delivery. Cause of stillbirth was assigned by algorithm. Results: From 2010 through 2018, 573,148 women were enrolled with delivery data obtained. Of the 552,547 births that reached 500 g or 20 weeks gestation, 15,604 were stillbirths; a rate of 28.2 stillbirths per 1000 births. The stillbirth rates were 19.3 in the Guatemala site, 23.8 in the African sites, and 33.3 in the Asian sites. Specifically, stillbirth rates were highest in the Pakistan site, which also documented a substantial decrease in stillbirth rates over the study period, from 56.0 per 1000 (95% CI 51.0, 61.0) in 2010 to 44.4 per 1000 (95% CI 39.1, 49.7) in 2018. The Nagpur, India site also documented a substantial decrease in stillbirths from 32.5 (95% CI 29.0, 36.1) to 16.9 (95% CI 13.9, 19.9) per 1000 in 2018; however, other sites had only small declines in stillbirth over the same period. Women who were less educated and older as well as those with less access to antenatal care and with vaginal assisted delivery were at increased risk of stillbirth. The major fetal causes of stillbirth were birth asphyxia (44.0% of stillbirths) and infectious causes (22.2%). The maternal conditions that were observed among those with stillbirth were obstructed or prolonged labor, antepartum hemorrhage and maternal infections. Conclusions: Over the study period, stillbirth rates have remained relatively high across all sites. With the exceptions of the Pakistan and Nagpur sites, Global Network sites did not observe substantial changes in their stillbirth rates. Women who were less educated and had less access to antenatal and obstetric care remained at the highest burden of stillbirth.Item The Global Network Neonatal Cause of Death algorithm for low-resource settings(Wiley, 2017) Garces, Ana L.; McClure, Elizabeth M.; Pérez, Wilton; Hambidge, K. Michael; Krebs, Nancy F.; Figueroa, Lester; Bose, Carl L.; Carlo, Waldemar A.; Tenge, Constance; Esamai, Fabian; Goudar, Shivaprasad S.; Saleem, Sarah; Patel, Archana B.; Chiwila, Melody; Chomba, Elwyn; Tshefu, Antoinette; Derman, Richard J.; Hibberd, Patricia L.; Bucher, Sherri; Liechty, Edward A.; Bauserman, Melissa; Moore, Janet L.; Koso-Thomas, Marion; Miodovnik, Menachem; Goldenberg, Robert L.; Pediatrics, School of MedicineAim: This study estimated the causes of neonatal death using an algorithm for low-resource areas, where 98% of the world's neonatal deaths occur. Methods: We enrolled women in India, Pakistan, Guatemala, the Democratic Republic of Congo, Kenya and Zambia from 2014 to 2016 and tracked their delivery and newborn outcomes for up to 28 days. Antenatal care and delivery symptoms were collected using a structured questionnaire, clinical observation and/or a physical examination. The Global Network Cause of Death algorithm was used to assign the cause of neonatal death, analysed by country and day of death. Results: One-third (33.1%) of the 3068 neonatal deaths were due to suspected infection, 30.8% to prematurity, 21.2% to asphyxia, 9.5% to congenital anomalies and 5.4% did not have a cause of death assigned. Prematurity and asphyxia-related deaths were more common on the first day of life (46.7% and 52.9%, respectively), while most deaths due to infection occurred after the first day of life (86.9%). The distribution of causes was similar to global data reported by other major studies. Conclusion: The Global Network algorithm provided a reliable cause of neonatal death in low-resource settings and can be used to inform public health strategies to reduce mortality.Item The Global Network Socioeconomic Status Index as a predictor of stillbirths, perinatal mortality, and neonatal mortality in rural communities in low and lower middle income country sites of the Global Network for Women’s and Children’s Health Research(PLOS, 2022-08-16) Patel, Archana B.; Bann, Carla M.; Kolhe, Cherryl S.; Lokangaka, Adrien; Tshefu, Antoinette; Bauserman, Melissa; Figueroa, Lester; Krebs, Nancy F.; Esamai, Fabian; Bucher, Sherri; Saleem, Sarah; Goldenberg, Robert L.; Chomba, Elwyn; Carlo, Waldemar A.; Goudar, Shivaprasad; Derman, Richard J.; Koso-Thomas, Marion; McClure, Elizabeth M.; Hibberd, Patricia L.; Pediatrics, School of MedicineBackground Globally, socioeconomic status (SES) is an important health determinant across a range of health conditions and diseases. However, measuring SES within low- and middle-income countries (LMICs) can be particularly challenging given the variation and diversity of LMIC populations. Objective The current study investigates whether maternal SES as assessed by the newly developed Global Network-SES Index is associated with pregnancy outcomes (stillbirths, perinatal mortality, and neonatal mortality) in six LMICs: Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan, and Zambia. Methods The analysis included data from 87,923 women enrolled in the Maternal and Newborn Health Registry of the NICHD-funded Global Network for Women’s and Children’s Health Research. Generalized estimating equations models were computed for each outcome by SES level (high, moderate, or low) and controlling for site, maternal age, parity, years of schooling, body mass index, and facility birth, including sampling cluster as a random effect. Results Women with low SES had significantly higher risks for stillbirth (p < 0.001), perinatal mortality (p = 0.001), and neonatal mortality (p = 0.005) than women with high SES. In addition, those with moderate SES had significantly higher risks of stillbirth (p = 0.003) and perinatal mortality (p = 0.008) in comparison to those with high SES. Conclusion The SES categories were associated with pregnancy outcomes, supporting the validity of the index as a non–income-based measure of SES for use in studies of pregnancy outcomes in LMICs.Item Trends and determinants of stillbirth in developing countries: results from the Global Network’s Population-Based Birth Registry(Springer Nature, 2018-06-22) Saleem, Sarah; Tikmani, Shiyam Sunder; McClure, Elizabeth M.; Moore, Janet L.; Azam, Syed Iqbal; Dhaded, Sangappa M.; Goudar, Shivaprasad S.; Garces, Ana; Figueroa, Lester; Marete, Irene; Tenge, Constance; Esamai, Fabian; Patel, Archana B.; Ali, Sumera Aziz; Naqvi, Farnaz; Mwenchanya, Musaku; Chomba, Elwyn; Carlo, Waldemar A.; Derman, Richard J.; Hibberd, Patricia L.; Bucher, Sherri; Liechty, Edward A.; Krebs, Nancy; Hambidge, K. Michael; Wallace, Dennis D.; Koso-Thomas, Marion; Miodovnik, Menachem; Goldenberg, Robert L.; Pediatrics, School of MedicineBackground: 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.Item Trends in the incidence of possible severe bacterial infection and case fatality rates in rural communities in Sub-Saharan Africa, South Asia and Latin America, 2010-2013: a multicenter prospective cohort study(BioMed Central, 2016-05-24) Hibberd, Patricia L.; Hansen, Nellie I.; Wang, Marie E.; Goudar, Shivaprasad S.; Pasha, Omrana; Esamai, Fabian; Chomba, Elwyn; Garces, Ana; Althabe, Fernando; Derman, Richard J.; Goldenberg, Robert L.; Liechty, Edward A.; Carlo, Waldemar A.; Hambidge, K. Michael; Krebs, Nancy F.; Buekens, Pierre; McClure, Elizabeth M.; Koso-Thomas, Marion; Patel, Archana B.; Department of Pediatrics, IU School of MedicineBackground Possible severe bacterial infections (pSBI) continue to be a leading cause of global neonatal mortality annually. With the recent publications of simplified antibiotic regimens for treatment of pSBI where referral is not possible, it is important to know how and where to target these regimens, but data on the incidence and outcomes of pSBI are limited. Methods We used data prospectively collected at 7 rural community-based sites in 6 low and middle income countries participating in the NICHD Global Network’s Maternal and Newborn Health Registry, between January 1, 2010 and December 31, 2013. Participants included pregnant women and their live born neonates followed for 6 weeks after delivery and assessed for maternal and infant outcomes. Results In a cohort of 248,539 infants born alive between 2010 and 2013, 32,088 (13 %) neonates met symptomatic criteria for pSBI. The incidence of pSBI during the first 6 weeks of life varied 10 fold from 3 % (Zambia) to 36 % (Pakistan), and overall case fatality rates varied 8 fold from 5 % (Kenya) to 42 % (Zambia). Significant variations in incidence of pSBI during the study period, with proportions decreasing in 3 sites (Argentina, Kenya and Nagpur, India), remaining stable in 3 sites (Zambia, Guatemala, Belgaum, India) and increasing in 1 site (Pakistan), cannot be explained solely by changing rates of facility deliveries. Case fatality rates did not vary over time. Conclusions In a prospective population based registry with trained data collectors, there were wide variations in the incidence and case fatality of pSBI in rural communities and in trends over time. Regardless of these variations, the burden of pSBI is still high and strategies to implement timely diagnosis and treatment are still urgently needed to reduce neonatal mortality.