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Item Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas(Springer Nature, 2024-05-07) Khan, Raiyan R.; Guerrero, Rafael F.; Wapner, Ronald J.; Hahn, Matthew W.; Raja, Anita; Salleb‑Aouissi, Ansaf; Grobman, William A.; Simhan, Hyagriv; Silver, Robert M.; Chung, Judith H.; Reddy, Uma M.; Radivojac, Predrag; Pe’er, Itsik; Haas, David M.; Obstetrics and Gynecology, School of MedicineAdverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.Item Helping Babies Breathe (HBB) training: What happens to knowledge and skills over time?(Springer Nature, 2016-11-22) Bang, Akash; Patel, Archana; Bellad, Roopa; Gisore, Peter; Goudar, Shivaprasad S.; Esamai, Fabian; Liechty, Edward A.; Meleth, Sreelatha; Goco, Norman; Niermeyer, Susan; Keenan, William; Kamath-Rayne, Beena D.; Little, George A.; Clarke, Susan B.; Flanagan, Victoria A.; Bucher, Sherri; Jain, Manish; Mujawar, Nilofer; Jain, Vinita; Rukunga, Janet; Mahantshetti, Niranjana; Dhaded, Sangappa; Bhandankar, Manisha; McClure, Elizabeth M.; Carlo, Waldemar A.; Wright, Linda L.; Hibberd, Patricia L.; Pediatrics, School of MedicineBackground: The first minutes after birth are critical to reducing neonatal mortality. Helping Babies Breathe (HBB) is a simulation-based neonatal resuscitation program for low resource settings. We studied the impact of initial HBB training followed by refresher training on the knowledge and skills of the birth attendants in facilities. Methods: We conducted HBB trainings in 71 facilities in the NICHD Global Network research sites (Nagpur and Belgaum, India and Eldoret, Kenya), with a 6:1 ratio of facility trainees to Master Trainers (MT). Because of staff turnover, some birth attendants (BA) were trained as they joined the delivery room staff, after the initial training was completed (catch-up initial training). We compared pass rates for skills and knowledge pre- and post- initial HBB training and following refresher training among active BAs. An Objective Structured Clinical Examination (OSCE) B tested resuscitation skill retention by comparing post-initial training performance with pre-refresher training performance. We identified factors associated with loss of skills in pre-refresher training performance using multivariable logistic regression analysis. Daily bag and mask ventilation practice, equipment checks and supportive supervision were stressed as part of training. Results: One hundred five MT (1.6 MT per facility) conducted initial and refresher HBB trainings for 835 BAs; 76% had no prior resuscitation training. Initial training improved knowledge and skills: the pass percentage for knowledge tests improved from 74 to 99% (p < 0.001). Only 5% could ventilate a newborn mannequin correctly before initial training but 97% passed the post-initial ventilation training test (p < 0.0001) and 99% passed the OSCE B resuscitation evaluation. During pre-refresher training evaluation, a mean of 6.7 (SD 2.49) months after the initial training, 99% passed the knowledge test, but the successful completion rate fell to 81% for the OSCE B resuscitation skills test. Characteristics associated with deterioration of resuscitation skills were BAs from tertiary care facilities, no prior resuscitation training, and the timing of training (initial vs. catch-up training). Conclusions: HBB training significantly improved neonatal resuscitation knowledge and skills. However, skills declined more than knowledge over time. Ongoing skills practice and monitoring, more frequent retesting, and refresher trainings are needed to maintain neonatal resuscitation skills.Item Perinatal outcomes after intrauterine growth restriction and umbilical artery Doppler pulsatility index of less than the fifth percentile(Taylor & Francis, 2021-03) Lewkowitz, Adam K.; Tuuli, Methodius G.; Cahill, Alison G.; Macones, George A.; Dicke, Jeffrey M.; Obstetrics and Gynecology, School of MedicineObjective: To analyze perinatal morbidity and stillbirth after intrauterine growth restriction (IUGR) with an umbilical artery Doppler pulsatility index (UA PI) less than the fifth centile.Study design: This retrospective cohort study included nonanomalous singleton, IUGR pregnancies receiving UA PI testing at a tertiary-care prenatal diagnostic center. Women with persistently elevated UA PI, absent or reversed end-diastolic flow on UA PI, or who had only one UA PI result were excluded. Low UA PI was defined as having ≥1 UA PI <5%. Women with low UA PI were matched by gestational age at IUGR diagnosis in a random 1 case: 4 control computer-generated algorithm to those with normal UA PI (≤95% and ≥5%). The primary outcome was composite neonatal morbidity and mortality (stillbirth, mechanical ventilation, sepsis, intraventricular hemorrhage, and necrotizing enterocolitis). Secondary outcomes included 5-minute Apgar, umbilical artery pH, delivery type, and interval from IUGR diagnosis to delivery. We compared outcomes after low UA PI to those after normal UA PI with multivariable logistic regression, adjusting for gestational age at delivery, betamethasone use, infant gender, and maternal factors.Results: Of the 1893 IUGR pregnancies, 25 (1.3%) had low UA PI <5% and were randomly matched via computer algorithm to 100 controls. There were no stillbirths in either group; the odds of composite neonatal morbidity was similar among IUGR pregnancies with UA PI <5% versus normal (adjusted odds ratio 0.89 (95% confidence interval 0.27-2.75)). There was no difference in 5-minute Apgars, umbilical artery pH, rate of cesarean delivery for fetal distress, or interval from IUGR diagnosis to delivery between the two groups.Conclusion: Among IUGR pregnancies, UA PI <5% is uncommon and not associated with improved neonatal outcomes compared to normal UA PI. These findings suggest low UA PI can continue to be managed as normal UA PI.Item Predictive Modeling for Perinatal Mortality in Resource-Limited Settings(American Medical Association, 2020-11-02) Shukla, Vivek V.; Eggleston, Barry; Ambalavanan, Namasivayam; McClure, Elizabeth M.; Mwenechanya, Musaku; Chomba, Elwyn; Bose, Carl; Bauserman, Melissa; Tshefu, Antoinette; Goudar, Shivaprasad S.; Derman, Richard J.; Garcés, Ana; Krebs, Nancy F.; Saleem, Sarah; Goldenberg, Robert L.; Patel, Archana; Hibberd, Patricia L.; Esamai, Fabian; Bucher, Sherri; Liechty, Edward A.; Koso-Thomas, Marion; Carlo, Waldemar A.; Pediatrics, School of MedicineImportance: The overwhelming majority of fetal and neonatal deaths occur in low- and middle-income countries. Fetal and neonatal risk assessment tools may be useful to predict the risk of death. Objective: To develop risk prediction models for intrapartum stillbirth and neonatal death. Design, setting, and participants: This cohort study used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Global Network for Women's and Children's Health Research population-based vital registry, including clinical sites in South Asia (India and Pakistan), Africa (Democratic Republic of Congo, Zambia, and Kenya), and Latin America (Guatemala). A total of 502 648 pregnancies were prospectively enrolled in the registry. Exposures: Risk factors were added sequentially into the data set in 4 scenarios: (1) prenatal, (2) predelivery, (3) delivery and day 1, and (4) postdelivery through day 2. Main outcomes and measures: Data sets were randomly divided into 10 groups of 3 analysis data sets including training (60%), test (20%), and validation (20%). Conventional and advanced machine learning modeling techniques were applied to assess predictive abilities using area under the curve (AUC) for intrapartum stillbirth and neonatal mortality. Results: All prenatal and predelivery models had predictive accuracy for both intrapartum stillbirth and neonatal mortality with AUC values 0.71 or less. Five of 6 models for neonatal mortality based on delivery/day 1 and postdelivery/day 2 had increased predictive accuracy with AUC values greater than 0.80. Birth weight was the most important predictor for neonatal death in both postdelivery scenarios with independent predictive ability with AUC values of 0.78 and 0.76, respectively. The addition of 4 other top predictors increased AUC to 0.83 and 0.87 for the postdelivery scenarios, respectively. Conclusions and relevance: Models based on prenatal or predelivery data had predictive accuracy for intrapartum stillbirths and neonatal mortality of AUC values 0.71 or less. Models that incorporated delivery data had good predictive accuracy for risk of neonatal mortality. Birth weight was the most important predictor for neonatal mortality.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 “There's no time limit on grief:” Women's perspectives on a novel reproductive grief screening tool(Elsevier, 2023-12-04) Bute, Jennifer J.; Brann, Maria; Buskmiller, Cara; Fredenburg, Michaelene; Communication Studies, School of Liberal ArtsObjective: Women who have experienced reproductive loss (i.e., miscarriage, stillbirth, abortion) evaluated the usefulness of a novel screening tool, Reproductive Grief Screen (RGS), to identify patients struggling with ongoing, complicated grief. Methods: This mixed-methods study involved U.S. women who had experienced reproductive loss. Online data collection resulted in 27 interviews and 282 surveys completed. Perceptions of and preferences about RGS were thematically analyzed. Chi square analyses assessed relationships between demographics and tool preferences. Results: RGS validated women's experiences with grief after reproductive loss. Women noted their providers may be unaware of their loss(es). Participants requested periodic screening using RGS beginning shortly after a loss (or during new patient intake) and occurring regularly (e.g., annually). Overall, women preferred completing RGS online before an appointment, though preferences varied by demographics (i.e., age, time since loss). Participants want providers to compassionately discuss RGS results with them and offer appropriate resources. Conclusion: The RGS can help identify largely ignored grief after reproductive loss. Innovation: Findings from group and individual interviews and a survey of women who have coped with reproductive loss suggest that use of a brief RGS tool could reshape clinical practice to aid women who might be facing complicated grief. Moreover, women expressed clear preferences for how to implement use of the RGS in clinical contexts.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 Validation of a Brief Measure for Complicated Grief Specific to Reproductive Loss(Springer Nature, 2023-04-20) Buskmiller, Cara; Grauerholz, Kathryn R.; Bute, Jennifer; Brann, Maria; Fredenburg, Michaelene; Refuerzo, Jerrie S.; Communication Studies, School of Liberal ArtsObjective: Complicated grief reactions follow some pregnancy outcomes, like miscarriage, stillbirth, neonatal death, infant death, selective reduction, or termination of pregnancy. Stigma can delay treatment and worsen outcomes. Screening tools such as the Edinburgh Postnatal Depression Scale detect complicated grief poorly, and specific tools for prolonged or complicated grief after a reproductive loss are cumbersome. In this study, a five-item questionnaire to detect complicated grief after reproductive loss of any type was designed and preliminary validated. Methods: A questionnaire patterned after the extensively validated Brief Grief Questionnaire (BGQ) was created by a group of physicians and lay advocates to employ non-traumatic but specific language related to grief after miscarriage, stillbirth, neonatal death, infant death, selective reduction, or termination of pregnancy. One hundred and forty women at a large academic center were recruited in person and via social media to validate the questionnaire with well-studied instruments for anxiety (7-item Panic Disorder Severity Scale, PDSS), trauma (22-item Impact of Events Scale), and reproductive grief and depressive symptoms (33-item Perinatal Grief Scale [PGS]). Results: The response rate was 74.9%. Of the 140 participants, 18 (12.8%) experienced their loss during high-risk pregnancies, and 65 (46.4%) were recruited via social media. Seventy-one (51%) respondents had a score > 4, a positive screen for the BGQ. On average, women experienced their loss 2 years prior to participation (IQR 1-5 years). Cronbach's alpha was 0.77 (95% CI: 0.69-0.83). The goodness of fit indices of the model met Fornell and Larker criteria (RMSEA = 0.167, CFI = 0.89, SRMR = 0.06). The AVE was 0.42 and the CR 0.78. Conclusions: This investigator-created screening tool is internally consistent and meets preliminary criteria for discriminant validity. This tool can be refined prior to testing for sensitivity and specificity in screening for complicated grief after a reproductive loss.