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1. Effects of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries: an individual participant data meta-analysis of 2 198 655 pregnancies

Author

Abdollahain, Mali, Savitri, Ary I., Salvesen, Kjell Åsmund, Bhattacharya, Sohinee, Uiterwaal, Cuno S.P.M., Staff, Annetine C., Andersen, Louise Bjoerkholt, Olive, Elisa Llurba, Daskalakis, George, Macleod, Maureen, Thilaganathan, Baskaran, Ramírez, Javier Arenas, Massé, Jacques, Audibert, Francois, Magnus, Per Minor, Sletner, Line, Baschat, Ahmet, Ohkuchi, Akihide, McAuliffe, Fionnuala M., West, Jane, Askie, Lisa M., Mone, Fionnuala, Farrar, Diane, Zimmerman, Peter A., Smits, Luc J.M., Riddell, Catherine, Kingdom, John C., van de Post, Joris, Illanes, Sebastián E., Holzman, Claudia, van Kuijk, Sander M.J., Carbillon, Lionel, Villa, Pia M., Eskild, Anne, Chappell, Lucy, Prefumo, Federico, Velauthar, Luxmi, Seed, Paul, van Oostwaard, Miriam, Verlohren, Stefan, Poston, Lucilla, Ferrazzi, Enrico, Vinter, Christina A., Nagata, Chie, Brown, Mark, Vollebregt, Karlijn C., Takeda, Satoru, Langenveld, Josje, Widmer, Mariana, Saito, Shigeru, Haavaldsen, Camilla, Carroli, Guillermo, Olsen, Jørn, Wolf, Hans, Zavaleta, Nelly, Eisensee, Inge, Vergani, Patrizia, Lumbiganon, Pisake, Makrides, Maria, Facchinetti, Fabio, Sequeira, Evan, Gibson, Robert, Ferrazzani, Sergio, Frusca, Tiziana, Figueiró-Filho, Ernesto A., Lapaire, Olav, Laivuori, Hannele, Lykke, Jacob A., Conde-Agudelo, Agustin, Galindo, Alberto, Mbah, Alfred, Betran, Ana Pilar, Herraiz, Ignacio, Trogstad, Lill, Smith, Gordon G.S., Steegers, Eric A.P., Salim, Read, Huang, Tianhua, Adank, Annemarijne, Zhang, Jun, Meschino, Wendy S., Browne, Joyce L., Allen, Rebecca E., Da Silva Costa, Fabricio, Klipstein-Grobusch, Kerstin, Jørgensen, Jan Stener, Forest, Jean-Claude, Rumbold, Alice R., Mol, Ben W., Giguère, Yves, Ganzevoort, Wessel, Odibo, Anthony O., Myers, Jenny, Yeo, SeonAe, Teede, Helena J., Goffinet, Francois, McCowan, Lesley, Pajkrt, Eva, Haddad, Bassam G., Dekker, Gustaaf, Kleinrouweler, Emily C., LeCarpentier, Édouard, Roberts, Claire T., Groen, Henk, Skråstad, Ragnhild Bergene, Heinonen, Seppo, Eero, Kajantie, Kenny, Louise C., Anggraini, Dewi, Souka, Athena, Cecatti, Jose, Monterio, Ilza, Coomarasamy, Arri, Smuk, Melanie, Pillalis, Athanasios, Crovetto, Francesca, Souza, Renato, Ann Hawkins, Lee, Gabbay- Benziv, Rinat, Riley, Richard, Snell, Kym, Archer, Lucinda, Figuera, Francesc, van Gelder, Marleen, Sheikh, Jameela, Allotey, John, Kew, Tania, Fernández-Félix, Borja M, Zamora, Javier, Khalil, Asma, and Thangaratinam, Shakila

Published
2022
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2. External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications (IPPIC) Network database: individual participant data meta-analysis

Author

Allotey, J, Whittle, R, Snell, K, Smuk, M, Townsend, R, von Dadelszen, P, Heazell, A, Magee, L, Smith, G, Sandall, J, Thilaganathan, B, Zamora, J, Riley, R, Khalil, A, Thangaratinam, S, Coomarasamy, A, Kwong, A, Savitri, A, Salvesen, K, Bhattacharya, S, Uiterwaal, C, Staff, A, Andersen, L, Olive, E, Redman, C, Sletner, L, Daskalakis, G, Macleod, M, Abdollahain, M, Ramirez, J, Masse, J, Audibert, F, Magnus, P, Jenum, A, Baschat, A, Ohkuchi, A, Mcauliffe, F, West, J, Askie, L, Mone, F, Farrar, D, Zimmerman, P, Smits, L, Riddell, C, Kingdom, J, van de Post, J, Illanes, S, Holzman, C, van Kuijk, S, Carbillon, L, Villa, P, Eskild, A, Chappell, L, Prefumo, F, Velauthar, L, Seed, P, van Oostwaard, M, Verlohren, S, Poston, L, Ferrazzi, E, Vinter, C, Nagata, C, Brown, M, Vollebregt, K, Takeda, S, Langenveld, J, Widmer, M, Saito, S, Haavaldsen, C, Carroli, G, Olsen, J, Wolf, H, Zavaleta, N, Eisensee, I, Vergani, P, Lumbiganon, P, Makrides, M, Facchinetti, F, Sequeira, E, Gibson, R, Ferrazzani, S, Frusca, T, Norman, J, Figueiro, E, Lapaire, O, Laivuori, H, Lykke, J, Conde-Agudelo, A, Galindo, A, Mbah, A, Betran, A, Herraiz, I, Trogstad, L, Steegers, E, Salim, R, Huang, T, Adank, A, Zhang, J, Meschino, W, Browne, J, Allen, R, Costa, F, Klipstein-Grobusch Browne, K, Crowther, C, Jorgensen, J, Forest, J, Rumbold, A, Mol, B, Giguere, Y, Kenny, L, Ganzevoort, W, Odibo, A, Myers, J, Yeo, S, Goffinet, F, Mccowan, L, Pajkrt, E, Teede, H, Haddad, B, Dekker, G, Kleinrouweler, E, Lecarpentier, E, Roberts, C, Groen, H, Skrastad, R, Heinonen, S, Eero, K, Anggraini, D, Souka, A, Cecatti, J, Monterio, I, Pillalis, A, Souza, R, Hawkins, L, Gabbay-Benziv, R, Crovetto, F, Figuera, F, Jorgensen, L, Dodds, J, Patel, M, Aviram, A, Papageorghiou, A, Khan, K, Allotey J., Whittle R., Snell K. I. E., Smuk M., Townsend R., von Dadelszen P., Heazell A. E. P., Magee L., Smith G. C. S., Sandall J., Thilaganathan B., Zamora J., Riley R. D., Khalil A., Thangaratinam S., Coomarasamy A., Kwong A., Savitri A. I., Salvesen K. A., Bhattacharya S., Uiterwaal C. S. P. M., Staff A. C., Andersen L. B., Olive E. L., Redman C., Sletner L., Daskalakis G., Macleod M., Abdollahain M., Ramirez J. A., Masse J., Audibert F., Magnus P. M., Jenum A. K., Baschat A., Ohkuchi A., McAuliffe F. M., West J., Askie L. M., Mone F., Farrar D., Zimmerman P. A., Smits L. J. M., Riddell C., Kingdom J. C., van de Post J., Illanes S. E., Holzman C., van Kuijk S. M. J., Carbillon L., Villa P. M., Eskild A., Chappell L., Prefumo F., Velauthar L., Seed P., van Oostwaard M., Verlohren S., Poston L., Ferrazzi E., Vinter C. A., Nagata C., Brown M., Vollebregt K. C., Takeda S., Langenveld J., Widmer M., Saito S., Haavaldsen C., Carroli G., Olsen J., Wolf H., Zavaleta N., Eisensee I., Vergani P., Lumbiganon P., Makrides M., Facchinetti F., Sequeira E., Gibson R., Ferrazzani S., Frusca T., Norman J. E., Figueiro E. A., Lapaire O., Laivuori H., Lykke J. A., Conde-Agudelo A., Galindo A., Mbah A., Betran A. P., Herraiz I., Trogstad L., Smith G. G. S., Steegers E. A. P., Salim R., Huang T., Adank A., Zhang J., Meschino W. S., Browne J. L., Allen R. E., Costa F. D. S., Klipstein-Grobusch Browne K., Crowther C. A., Jorgensen J. S., Forest J. -C., Rumbold A. R., Mol B. W., Giguere Y., Kenny L. C., Ganzevoort W., Odibo A. O., Myers J., Yeo S. A., Goffinet F., McCowan L., Pajkrt E., Teede H. J., Haddad B. G., Dekker G., Kleinrouweler E. C., LeCarpentier E., Roberts C. T., Groen H., Skrastad R. B., Heinonen S., Eero K., Anggraini D., Souka A., Cecatti J. G., Monterio I., Pillalis A., Souza R., Hawkins L. A., Gabbay-Benziv R., Crovetto F., Figuera F., Jorgensen L., Dodds J., Patel M., Aviram A., Papageorghiou A., Khan K., Allotey, J, Whittle, R, Snell, K, Smuk, M, Townsend, R, von Dadelszen, P, Heazell, A, Magee, L, Smith, G, Sandall, J, Thilaganathan, B, Zamora, J, Riley, R, Khalil, A, Thangaratinam, S, Coomarasamy, A, Kwong, A, Savitri, A, Salvesen, K, Bhattacharya, S, Uiterwaal, C, Staff, A, Andersen, L, Olive, E, Redman, C, Sletner, L, Daskalakis, G, Macleod, M, Abdollahain, M, Ramirez, J, Masse, J, Audibert, F, Magnus, P, Jenum, A, Baschat, A, Ohkuchi, A, Mcauliffe, F, West, J, Askie, L, Mone, F, Farrar, D, Zimmerman, P, Smits, L, Riddell, C, Kingdom, J, van de Post, J, Illanes, S, Holzman, C, van Kuijk, S, Carbillon, L, Villa, P, Eskild, A, Chappell, L, Prefumo, F, Velauthar, L, Seed, P, van Oostwaard, M, Verlohren, S, Poston, L, Ferrazzi, E, Vinter, C, Nagata, C, Brown, M, Vollebregt, K, Takeda, S, Langenveld, J, Widmer, M, Saito, S, Haavaldsen, C, Carroli, G, Olsen, J, Wolf, H, Zavaleta, N, Eisensee, I, Vergani, P, Lumbiganon, P, Makrides, M, Facchinetti, F, Sequeira, E, Gibson, R, Ferrazzani, S, Frusca, T, Norman, J, Figueiro, E, Lapaire, O, Laivuori, H, Lykke, J, Conde-Agudelo, A, Galindo, A, Mbah, A, Betran, A, Herraiz, I, Trogstad, L, Steegers, E, Salim, R, Huang, T, Adank, A, Zhang, J, Meschino, W, Browne, J, Allen, R, Costa, F, Klipstein-Grobusch Browne, K, Crowther, C, Jorgensen, J, Forest, J, Rumbold, A, Mol, B, Giguere, Y, Kenny, L, Ganzevoort, W, Odibo, A, Myers, J, Yeo, S, Goffinet, F, Mccowan, L, Pajkrt, E, Teede, H, Haddad, B, Dekker, G, Kleinrouweler, E, Lecarpentier, E, Roberts, C, Groen, H, Skrastad, R, Heinonen, S, Eero, K, Anggraini, D, Souka, A, Cecatti, J, Monterio, I, Pillalis, A, Souza, R, Hawkins, L, Gabbay-Benziv, R, Crovetto, F, Figuera, F, Jorgensen, L, Dodds, J, Patel, M, Aviram, A, Papageorghiou, A, Khan, K, Allotey J., Whittle R., Snell K. I. E., Smuk M., Townsend R., von Dadelszen P., Heazell A. E. P., Magee L., Smith G. C. S., Sandall J., Thilaganathan B., Zamora J., Riley R. D., Khalil A., Thangaratinam S., Coomarasamy A., Kwong A., Savitri A. I., Salvesen K. A., Bhattacharya S., Uiterwaal C. S. P. M., Staff A. C., Andersen L. B., Olive E. L., Redman C., Sletner L., Daskalakis G., Macleod M., Abdollahain M., Ramirez J. A., Masse J., Audibert F., Magnus P. M., Jenum A. K., Baschat A., Ohkuchi A., McAuliffe F. M., West J., Askie L. M., Mone F., Farrar D., Zimmerman P. A., Smits L. J. M., Riddell C., Kingdom J. C., van de Post J., Illanes S. E., Holzman C., van Kuijk S. M. J., Carbillon L., Villa P. M., Eskild A., Chappell L., Prefumo F., Velauthar L., Seed P., van Oostwaard M., Verlohren S., Poston L., Ferrazzi E., Vinter C. A., Nagata C., Brown M., Vollebregt K. C., Takeda S., Langenveld J., Widmer M., Saito S., Haavaldsen C., Carroli G., Olsen J., Wolf H., Zavaleta N., Eisensee I., Vergani P., Lumbiganon P., Makrides M., Facchinetti F., Sequeira E., Gibson R., Ferrazzani S., Frusca T., Norman J. E., Figueiro E. A., Lapaire O., Laivuori H., Lykke J. A., Conde-Agudelo A., Galindo A., Mbah A., Betran A. P., Herraiz I., Trogstad L., Smith G. G. S., Steegers E. A. P., Salim R., Huang T., Adank A., Zhang J., Meschino W. S., Browne J. L., Allen R. E., Costa F. D. S., Klipstein-Grobusch Browne K., Crowther C. A., Jorgensen J. S., Forest J. -C., Rumbold A. R., Mol B. W., Giguere Y., Kenny L. C., Ganzevoort W., Odibo A. O., Myers J., Yeo S. A., Goffinet F., McCowan L., Pajkrt E., Teede H. J., Haddad B. G., Dekker G., Kleinrouweler E. C., LeCarpentier E., Roberts C. T., Groen H., Skrastad R. B., Heinonen S., Eero K., Anggraini D., Souka A., Cecatti J. G., Monterio I., Pillalis A., Souza R., Hawkins L. A., Gabbay-Benziv R., Crovetto F., Figuera F., Jorgensen L., Dodds J., Patel M., Aviram A., Papageorghiou A., and Khan K.

Abstract

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overa

Published
2022

3. External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications (IPPIC) Network database: individual participant data meta-analysis

Author

Allotey, J., Whittle, R., Snell, K. I. E., Smuk, M., Townsend, R., von Dadelszen, P., Heazell, A. E. P., Magee, L., Smith, G. C. S., Sandall, J., Thilaganathan, B., Zamora, J., Riley, R. D., Khalil, A., Thangaratinam, S., Coomarasamy, A., Kwong, A., Savitri, A. I., Salvesen, K. A., Bhattacharya, S., Uiterwaal, C. S. P. M., Staff, A. C., Andersen, L. B., Olive, E. L., Redman, C., Sletner, L., Daskalakis, G., Macleod, M., Abdollahain, M., Ramirez, J. A., Masse, J., Audibert, F., Magnus, P. M., Jenum, A. K., Baschat, A., Ohkuchi, A., Mcauliffe, F. M., West, J., Askie, L. M., Mone, F., Farrar, D., Zimmerman, P. A., Smits, L. J. M., Riddell, C., Kingdom, J. C., van de Post, J., Illanes, S. E., Holzman, C., van Kuijk, S. M. J., Carbillon, L., Villa, P. M., Eskild, A., Chappell, L., Prefumo, F., Velauthar, L., Seed, P., van Oostwaard, M., Verlohren, S., Poston, L., Ferrazzi, E., Vinter, C. A., Nagata, C., Brown, M., Vollebregt, K. C., Takeda, S., Langenveld, J., Widmer, M., Saito, S., Haavaldsen, C., Carroli, G., Olsen, J., Wolf, H., Zavaleta, N., Eisensee, I., Vergani, P., Lumbiganon, P., Makrides, M., Facchinetti, F., Sequeira, E., Gibson, R., Ferrazzani, S., Frusca, T., Norman, J. E., Figueiro, E. A., Lapaire, O., Laivuori, H., Lykke, J. A., Conde-Agudelo, A., Galindo, A., Mbah, A., Betran, A. P., Herraiz, I., Trogstad, L., Smith, G. G. S., Steegers, E. A. P., Salim, R., Huang, T., Adank, A., Zhang, J., Meschino, W. S., Browne, J. L., Allen, R. E., Costa, F. D. S., Klipstein-Grobusch Browne, K., Crowther, C. A., Jorgensen, J. S., Forest, J. -C., Rumbold, A. R., Mol, B. W., Giguere, Y., Kenny, L. C., Ganzevoort, W., Odibo, A. O., Myers, J., Yeo, S. A., Goffinet, F., Mccowan, L., Pajkrt, E., Teede, H. J., Haddad, B. G., Dekker, G., Kleinrouweler, E. C., Lecarpentier, E., Roberts, C. T., Groen, H., Skrastad, R. B., Heinonen, S., Eero, K., Anggraini, D., Souka, A., Cecatti, J. G., Monterio, I., Pillalis, A., Souza, R., Hawkins, L. A., Gabbay-Benziv, R., Crovetto, F., Figuera, F., Jorgensen, L., Dodds, J., Patel, M., Aviram, A., Papageorghiou, A., Khan, K., Clinicum, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Allotey, J, Whittle, R, Snell, K, Smuk, M, Townsend, R, von Dadelszen, P, Heazell, A, Magee, L, Smith, G, Sandall, J, Thilaganathan, B, Zamora, J, Riley, R, Khalil, A, Thangaratinam, S, Coomarasamy, A, Kwong, A, Savitri, A, Salvesen, K, Bhattacharya, S, Uiterwaal, C, Staff, A, Andersen, L, Olive, E, Redman, C, Sletner, L, Daskalakis, G, Macleod, M, Abdollahain, M, Ramirez, J, Masse, J, Audibert, F, Magnus, P, Jenum, A, Baschat, A, Ohkuchi, A, Mcauliffe, F, West, J, Askie, L, Mone, F, Farrar, D, Zimmerman, P, Smits, L, Riddell, C, Kingdom, J, van de Post, J, Illanes, S, Holzman, C, van Kuijk, S, Carbillon, L, Villa, P, Eskild, A, Chappell, L, Prefumo, F, Velauthar, L, Seed, P, van Oostwaard, M, Verlohren, S, Poston, L, Ferrazzi, E, Vinter, C, Nagata, C, Brown, M, Vollebregt, K, Takeda, S, Langenveld, J, Widmer, M, Saito, S, Haavaldsen, C, Carroli, G, Olsen, J, Wolf, H, Zavaleta, N, Eisensee, I, Vergani, P, Lumbiganon, P, Makrides, M, Facchinetti, F, Sequeira, E, Gibson, R, Ferrazzani, S, Frusca, T, Norman, J, Figueiro, E, Lapaire, O, Laivuori, H, Lykke, J, Conde-Agudelo, A, Galindo, A, Mbah, A, Betran, A, Herraiz, I, Trogstad, L, Steegers, E, Salim, R, Huang, T, Adank, A, Zhang, J, Meschino, W, Browne, J, Allen, R, Costa, F, Klipstein-Grobusch Browne, K, Crowther, C, Jorgensen, J, Forest, J, Rumbold, A, Mol, B, Giguere, Y, Kenny, L, Ganzevoort, W, Odibo, A, Myers, J, Yeo, S, Goffinet, F, Mccowan, L, Pajkrt, E, Teede, H, Haddad, B, Dekker, G, Kleinrouweler, E, Lecarpentier, E, Roberts, C, Groen, H, Skrastad, R, Heinonen, S, Eero, K, Anggraini, D, Souka, A, Cecatti, J, Monterio, I, Pillalis, A, Souza, R, Hawkins, L, Gabbay-Benziv, R, Crovetto, F, Figuera, F, Jorgensen, L, Dodds, J, Patel, M, Aviram, A, Papageorghiou, A, Khan, K, Tampere University, Obstetrics and Gynaecology, APH - Quality of Care, Amsterdam Reproduction & Development (AR&D), APH - Personalized Medicine, APH - Digital Health, and Obstetrics and gynaecology

Subjects
Calibration (statistics), Perinatal Death, Overfitting, Cohort Studies, Fetal Development, 0302 clinical medicine, Discriminative model, 3123 Gynaecology and paediatrics, Models, Pregnancy, GROWTH RESTRICTION, Statistics, Medicine, Prenatal, 030212 general & internal medicine, Ultrasonography, RISK, 030219 obstetrics & reproductive medicine, PRETERM, Radiological and Ultrasound Technology, LOW-DOSE ASPIRIN, DIAGNOSIS TRIPOD, Obstetrics and Gynecology, General Medicine, Statistical, Stillbirth, Prognosis, Pregnancy Complication, external validation, individual participant data, intrauterine death, prediction model, stillbirth, Female, Humans, Infant, Newborn, Models, Statistical, Pregnancy Complications, Regression Analysis, Risk Assessment, Ultrasonography, Prenatal, 3. Good health, PREECLAMPSIA, Meta-analysis, Human, Cohort study, Prognosi, MEDLINE, Regression Analysi, WEEKS GESTATION, 03 medical and health sciences, VELOCIMETRY, Radiology, Nuclear Medicine and imaging, RECURRENCE, business.industry, Infant, Newborn, R1, HYPERTENSIVE DISORDERS, Reproductive Medicine, Sample size determination, Cohort Studie, RG, business, RA, Predictive modelling
Abstract

Objective Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. Conclusions The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. (c) 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Published
2022
Full Text
View/download PDF

4. Effects of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries: an individual participant data meta-analysis of 2 198 655 pregnancies

Author

Sheikh, Jameela, primary, Allotey, John, additional, Kew, Tania, additional, Fernández-Félix, Borja M, additional, Zamora, Javier, additional, Khalil, Asma, additional, Thangaratinam, Shakila, additional, Abdollahain, Mali, additional, Savitri, Ary I., additional, Salvesen, Kjell Åsmund, additional, Bhattacharya, Sohinee, additional, Uiterwaal, Cuno S.P.M., additional, Staff, Annetine C., additional, Andersen, Louise Bjoerkholt, additional, Olive, Elisa Llurba, additional, Daskalakis, George, additional, Macleod, Maureen, additional, Thilaganathan, Baskaran, additional, Ramírez, Javier Arenas, additional, Massé, Jacques, additional, Audibert, Francois, additional, Magnus, Per Minor, additional, Sletner, Line, additional, Baschat, Ahmet, additional, Ohkuchi, Akihide, additional, McAuliffe, Fionnuala M., additional, West, Jane, additional, Askie, Lisa M., additional, Mone, Fionnuala, additional, Farrar, Diane, additional, Zimmerman, Peter A., additional, Smits, Luc J.M., additional, Riddell, Catherine, additional, Kingdom, John C., additional, van de Post, Joris, additional, Illanes, Sebastián E., additional, Holzman, Claudia, additional, van Kuijk, Sander M.J., additional, Carbillon, Lionel, additional, Villa, Pia M., additional, Eskild, Anne, additional, Chappell, Lucy, additional, Prefumo, Federico, additional, Velauthar, Luxmi, additional, Seed, Paul, additional, van Oostwaard, Miriam, additional, Verlohren, Stefan, additional, Poston, Lucilla, additional, Ferrazzi, Enrico, additional, Vinter, Christina A., additional, Nagata, Chie, additional, Brown, Mark;, additional, Vollebregt, Karlijn C., additional, Takeda, Satoru, additional, Langenveld, Josje, additional, Widmer, Mariana, additional, Saito, Shigeru, additional, Haavaldsen, Camilla, additional, Carroli, Guillermo, additional, Olsen, Jørn, additional, Wolf, Hans, additional, Zavaleta, Nelly, additional, Eisensee, Inge, additional, Vergani, Patrizia, additional, Lumbiganon, Pisake, additional, Makrides, Maria, additional, Facchinetti, Fabio, additional, Sequeira, Evan, additional, Gibson, Robert, additional, Ferrazzani, Sergio, additional, Frusca, Tiziana, additional, Figueiró-Filho, Ernesto A., additional, Lapaire, Olav, additional, Laivuori, Hannele, additional, Lykke, Jacob A., additional, Conde-Agudelo, Agustin, additional, Galindo, Alberto, additional, Mbah, Alfred, additional, Betran, Ana Pilar, additional, Herraiz, Ignacio, additional, Trogstad, Lill, additional, Smith, Gordon G.S., additional, Steegers, Eric A.P., additional, Salim, Read, additional, Huang, Tianhua, additional, Adank, Annemarijne, additional, Zhang, Jun, additional, Meschino, Wendy S., additional, Browne, Joyce L., additional, Allen, Rebecca E., additional, Da Silva Costa, Fabricio, additional, Klipstein-Grobusch, Kerstin, additional, Jørgensen, Jan Stener, additional, Forest, Jean-Claude, additional, Rumbold, Alice R., additional, Mol, Ben W., additional, Giguère, Yves, additional, Ganzevoort, Wessel, additional, Odibo, Anthony O., additional, Myers, Jenny, additional, Yeo, SeonAe, additional, Teede, Helena J., additional, Goffinet, Francois, additional, McCowan, Lesley, additional, Pajkrt, Eva, additional, Haddad, Bassam G., additional, Dekker, Gustaaf, additional, Kleinrouweler, Emily C., additional, LeCarpentier, Édouard, additional, Roberts, Claire T., additional, Groen, Henk, additional, Skråstad, Ragnhild Bergene, additional, Heinonen, Seppo, additional, Eero, Kajantie, additional, Kenny, Louise C., additional, Anggraini, Dewi, additional, Souka, Athena, additional, Cecatti, Jose, additional, Monterio, Ilza, additional, Coomarasamy, Arri, additional, Smuk, Melanie, additional, Pillalis, Athanasios, additional, Crovetto, Francesca, additional, Souza, Renato, additional, Ann Hawkins, Lee, additional, Gabbay- Benziv, Rinat, additional, Riley, Richard, additional, Snell, Kym, additional, Archer, Lucinda, additional, Figuera, Francesc, additional, and van Gelder, Marleen, additional

Published
2022
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5. Effects of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries: an individual participant data meta-analysis of 2 198 655 pregnancies

Author

Jameela Sheikh, John Allotey, Tania Kew, Borja M Fernández-Félix, Javier Zamora, Asma Khalil, Shakila Thangaratinam, Mali Abdollahain, Ary I. Savitri, Kjell Åsmund Salvesen, Sohinee Bhattacharya, Cuno S.P.M. Uiterwaal, Annetine C. Staff, Louise Bjoerkholt Andersen, Elisa Llurba Olive, George Daskalakis, Maureen Macleod, Baskaran Thilaganathan, Javier Arenas Ramírez, Jacques Massé, Francois Audibert, Per Minor Magnus, Line Sletner, Ahmet Baschat, Akihide Ohkuchi, Fionnuala M. McAuliffe, Jane West, Lisa M. Askie, Fionnuala Mone, Diane Farrar, Peter A. Zimmerman, Luc J.M. Smits, Catherine Riddell, John C. Kingdom, Joris van de Post, Sebastián E. Illanes, Claudia Holzman, Sander M.J. van Kuijk, Lionel Carbillon, Pia M. Villa, Anne Eskild, Lucy Chappell, Federico Prefumo, Luxmi Velauthar, Paul Seed, Miriam van Oostwaard, Stefan Verlohren, Lucilla Poston, Enrico Ferrazzi, Christina A. Vinter, Chie Nagata, Mark, Brown, Karlijn C. Vollebregt, Satoru Takeda, Josje Langenveld, Mariana Widmer, Shigeru Saito, Camilla Haavaldsen, Guillermo Carroli, Jørn Olsen, Hans Wolf, Nelly Zavaleta, Inge Eisensee, Patrizia Vergani, Pisake Lumbiganon, Maria Makrides, Fabio Facchinetti, Evan Sequeira, Robert Gibson, Sergio Ferrazzani, Tiziana Frusca, Ernesto A. Figueiró-Filho, Olav Lapaire, Hannele Laivuori, Jacob A. Lykke, Agustin Conde-Agudelo, Alberto Galindo, Alfred Mbah, Ana Pilar Betran, Ignacio Herraiz, Lill Trogstad, Gordon G.S. Smith, Eric A.P. Steegers, Read Salim, Tianhua Huang, Annemarijne Adank, Jun Zhang, Wendy S. Meschino, Joyce L. Browne, Rebecca E. Allen, Fabricio Da Silva Costa, Kerstin Klipstein-Grobusch, Jan Stener Jørgensen, Jean-Claude Forest, Alice R. Rumbold, Ben W. Mol, Yves Giguère, Wessel Ganzevoort, Anthony O. Odibo, Jenny Myers, SeonAe Yeo, Helena J. Teede, Francois Goffinet, Lesley McCowan, Eva Pajkrt, Bassam G. Haddad, Gustaaf Dekker, Emily C. Kleinrouweler, Édouard LeCarpentier, Claire T. Roberts, Henk Groen, Ragnhild Bergene Skråstad, Seppo Heinonen, Kajantie Eero, Louise C. Kenny, Dewi Anggraini, Athena Souka, Jose Cecatti, Ilza Monterio, Arri Coomarasamy, Melanie Smuk, Athanasios Pillalis, Francesca Crovetto, Renato Souza, Lee Ann Hawkins, Rinat Gabbay- Benziv, Richard Riley, Kym Snell, Lucinda Archer, Francesc Figuera, Marleen van Gelder, Graduate School, Obstetrics and Gynaecology, APH - Quality of Care, ARD - Amsterdam Reproduction and Development, APH - Personalized Medicine, and APH - Digital Health

Subjects
General Medicine
Abstract

Background: Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions. Methods: For this individual participant data (IPD) meta-analysis we used data from the International Prediction of Pregnancy Complications (IPPIC) Network of studies on pregnancy complications; the full dataset comprised 94 studies, 53 countries, and 4 539 640 pregnancies. We included studies that reported perinatal outcomes (neonatal death, stillbirth, preterm birth, and small-for-gestational-age babies) in at least two racial or ethnic groups (White, Black, south Asian, Hispanic, or other). For our two-step random-effects IPD meta-analysis, we did multiple imputations for confounder variables (maternal age, BMI, parity, and level of maternal education) selected with a directed acyclic graph. The primary outcomes were neonatal mortality and stillbirth. Secondary outcomes were preterm birth and a small-for-gestational-age baby. We estimated the association of race and ethnicity with perinatal outcomes using a multivariate logistic regression model and reported this association with odds ratios (ORs) and 95% CIs. We also did a subgroup analysis of studies by geographical region. Findings: 51 studies from 20 high-income and upper-middle-income countries, comprising 2 198 655 pregnancies, were eligible for inclusion in this IPD meta-analysis. Neonatal death was twice as likely in babies born to Black women than in babies born to White women (OR 2·00, 95% CI 1·44–2·78), as was stillbirth (2·16, 1·46–3·19), and babies born to Black women were at increased risk of preterm birth (1·65, 1·46–1·88) and being small for gestational age (1·39, 1·13–1·72). Babies of women categorised as Hispanic had a three-times increased risk of neonatal death (OR 3·34, 95% CI 2·77–4·02) than did those born to White women, and those born to south Asian women were at increased risk of preterm birth (OR 1·26, 95% CI 1·07–1·48) and being small for gestational age (1·61, 1·32–1·95). The effects of race and ethnicity on preterm birth and small-for-gestational-age babies did not vary across regions. Interpretation: Globally, among underserved groups, babies born to Black women had consistently poorer perinatal outcomes than White women after adjusting for maternal characteristics, although the risks varied for other groups. The effects of race and ethnicity on adverse perinatal outcomes did not vary by region. Funding: National Institute for Health and Care Research, Wellbeing of Women.

Published
2022

6. External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications ( <scp>IPPIC</scp> ) Network database: individual participant data meta‐analysis

Author

Allotey, J, Whittle, R, Snell, KIE, Smuk, M, Townsend, R, Dadelszen, P, Heazell, AEP, Magee, L, Smith, GCS, Sandall, J, Thilaganathan, B, Zamora, J, Riley, RD, Khalil, A, Thangaratinam, S, Coomarasamy, A, Kwong, A, Savitri, AI, Salvesen, KÅ, Bhattacharya, S, Uiterwaal, CSPM, Staff, AC, Andersen, LB, Olive, EL, Redman, C, Sletner, L, Daskalakis, G, Macleod, M, Abdollahain, M, Ramírez, JA, Massé, J, Audibert, F, Magnus, PM, Jenum, AK, Baschat, A, Ohkuchi, A, McAuliffe, FM, West, J, Askie, LM, Mone, F, Farrar, D, Zimmerman, PA, Smits, LJM, Riddell, C, Kingdom, JC, Post, J, Illanes, SE, Holzman, C, Kuijk, SMJ, Carbillon, L, Villa, PM, Eskild, A, Chappell, L, Prefumo, F, Velauthar, L, Seed, P, Oostwaard, M, Verlohren, S, Poston, L, Ferrazzi, E, Vinter, CA, Nagata, C, Brown, M, Vollebregt, KC, Takeda, S, Langenveld, J, Widmer, M, Saito, S, Haavaldsen, C, Carroli, G, Olsen, J, Wolf, H, Zavaleta, N, Eisensee, I, Vergani, P, Lumbiganon, P, Makrides, M, Facchinetti, F, Sequeira, E, Gibson, R, Ferrazzani, S, Frusca, T, Norman, JE, Figueiró‐Filho, EA, Lapaire, O, Laivuori, H, Lykke, JA, Conde‐Agudelo, A, Galindo, A, Mbah, A, Betran, AP, Herraiz, I, Trogstad, L, Smith, GGS, Steegers, EAP, Salim, R, Huang, T, Adank, A, Zhang, J, Meschino, WS, Browne, JL, Allen, RE, Costa, F Da Silva, Klipstein‐Grobusch, K, Crowther, CA, Jørgensen, JS, Forest, J‐C, Rumbold, AR, Mol, BW, Giguère, Y, Kenny, LC, Ganzevoort, W, Odibo, AO, Myers, J, Yeo, SA, Goffinet, F, McCowan, L, Pajkrt, E, Teede, HJ, Haddad, BG, Dekker, G, Kleinrouweler, EC, LeCarpentier, É, Roberts, CT, Groen, H, Skråstad, RB, Heinonen, S, Eero, K, Anggraini, D, Souka, A, Cecatti, JG, Monterio, I, Pillalis, A, Souza, R, Hawkins, LA, Gabbay‐Benziv, R, Crovetto, F, Figuera, F, Jorgensen, L, Dodds, J, Patel, M, Aviram, A, Papageorghiou, A, and Khan, K

Abstract

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at risk can guide decisions on closer surveillance or timing of birth to prevent fetal death.Prognostic models have been developed to predict the risk of stillbirth, but none have yet been externally validated. We externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods: We searched Medline, EMBASE, DH-DATA and AMED databases from inception to December 2020 to identify stillbirth prediction models. We included studies that developed or updated prediction models for stillbirth for use at any time during pregnancy. IPD from cohorts within the International Prediction of Pregnancy Complication (IPPIC) Network were used to externally validate the identified prediction models whose individual variables were available in the IPD. We assessed the risk of bias of the models and IPD using PROBAST, and reported discriminative performance using the C-statistic, and calibration performance using calibration plots, calibration slopeand calibration-in-the-large. We estimated performance measures separately in each study, and then summarised across studies using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results: We identified 17 studies reporting the development of 40 prognostic models for stillbirth. None of the models were previously externally validated, and only a fifth (20%, 8/40) reported the full model equation. We were able to validate three of these models using the IPD from 19 cohort studies (491,201 pregnant women) within the IPPIC Network database. Based on evaluating their development studies, all three models had an overall high risk of bias according to PROBAST. In our IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65; summary calibration slopes of 0.40to 0.88, and generally with observed risks predictions that were too extreme compared to observed risks; and little to no clinical utility as assessed by net benefit. However, there remained uncertainty in performance for some models due to small available sample sizes. Conclusion: The three validated models generally showed poor and uncertain predictive performancein new data, with limited evidence to support their clinical application. Findings suggest methodological shortcomings in their development including overfitting of models. Further research is needed to further validate these and other models, identify stronger prognostic factors, and to develop more robust prediction models

Published
2021

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