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1. Enabling precision medicine in neonatology, an integrated repository for preterm birth research

Author

Sirota, Marina, Thomas, Cristel G., Liu, Rebecca, Zuhl, Maya, Banerjee, Payal, Wong, Ronald J., Quaintance, Cecele C., Leite, Rita, Chubiz, Jessica, Anderson, Rebecca, Chappell, Joanne, Kim, Mara, Grobman, William, Zhang, Ge, Rokas, Antonis, Muglia, Louis J., Ober, Carol, England, Sarah K., Macones, George, Driscoll, Deborah, Parry, Samuel, Shaw, Gary M., Stevenson, David K., Simpson, Joe Leigh, Thomson, Elizabeth, and Butte, Atul J.

Subjects
0301 basic medicine, Statistics and Probability, medicine.medical_specialty, Data Descriptor, Computer science, Reproductive disorders, Reproductive health and childbirth, Library and Information Sciences, computer.software_genre, Low Birth Weight and Health of the Newborn, Data publication and archiving, Education, 03 medical and health sciences, 0302 clinical medicine, Preterm, Infant Mortality, medicine, Genetics, Neonatology, Aetiology, Author Correction, Pediatric, Human Genome, Perinatal Period - Conditions Originating in Perinatal Period, Precision medicine, Data science, March of Dimes Prematurity Research Centers, Computer Science Applications, 030104 developmental biology, Good Health and Well Being, Data integration, Generic health relevance, Statistics, Probability and Uncertainty, computer, 030217 neurology & neurosurgery, 2.6 Resources and infrastructure (aetiology), Information Systems
Abstract

Preterm birth, or the delivery of an infant prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. In the last decade, the advent and continued development of molecular profiling technologies has enabled researchers to generate vast amount of ‘omics’ data, which together with integrative computational approaches, can help refine the current knowledge about disease mechanisms, diagnostics, and therapeutics. Here we describe the March of Dimes’ Database for Preterm Birth Research (http://www.immport.org/resources/mod), a unique resource that contains a variety of ‘omics’ datasets related to preterm birth. The database is open publicly, and as of January 2018, links 13 molecular studies with data across tens of thousands of patients from 6 measurement modalities. The data in the repository are highly diverse and include genomic, transcriptomic, immunological, and microbiome data. Relevant datasets are augmented with additional molecular characterizations of almost 25,000 biological samples from public databases. We believe our data-sharing efforts will lead to enhanced research collaborations and coordination accelerating the overall pace of discovery in preterm birth research.

Published
2018

2. Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index

Author

Ferreo, David M., Larson, Jim, Jacobsson, Bo, Di Renzo, Gian Carlo, Norman, Jane E., Martin Jr., James N., D'Alton, Mary, Castelazo, Ernesto, Howson, Chris P., Sengpiel, Verena, Bottai, Matteo, Mayo, Jonathan A., Shaw, Gary M., Verdenik, Ivan, Tul, Nataša, Cairns-Smith, Sarah, Velebil, Petr, Rushwan, Hamid, Arulkumaran, Sabaratnam, Howse, Jennifer L., and Simpson, Joe Leigh

Subjects
Public health, Premature infants, Infants--Mortality--Prevention, Developed countries
Abstract

Background: Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice. Methods: We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and population-attributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors. Findings: Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6–6.0 and 2.8–5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25–50% and 11–16% of excess population attributable risk, respectively (p < 0.001). The importance of nulliparity and male sex on population attributable risk was driven by high prevalence despite low odds ratios for individual women. More than 65% of the total aggregated risk of preterm birth within each country lacks a plausible biologic explanation, and 63% of difference between countries cannot be explained with known factors; thus, research is necessary to elucidate the underlying mechanisms of preterm birth and, hence, therapeutic intervention. Surprisingly, variation in prevalence of known risk factors accounted for less than 35% of the difference in preterm birth rates between countries. Known risk factors had an area under the curve of less than 0.7 in ROC analysis of preterm birth prediction within countries. These data suggest that other influences, as yet unidentified, are involved in preterm birth. Further research into biological mechanisms is warranted. Conclusions: We have quantified the causes of variation in preterm birth rates among countries with very high human development index. The paucity of explicit and currently identified factors amenable to intervention illustrates the limited impact of changes possible through current clinical practice and policy interventions. Our research highlights the urgent need for research into underlying biological causes of preterm birth, which alone are likely to lead to innovative and efficacious interventions.

Published
2016
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3. Salute to a giant ... Robert Geoffrey Edwards

Author

Ahuja, Kamal, Bennett, Fiona, Cohen, Jacques, Edwards, Ruth, Pritchard, Huw, Silver, Ann, Sirlin, Julio, Slee, John, Abse, Dannie, Ashwood-Smith, M. J., Bavister, Barry, Bedford, J. Michael, Beier, Henning M., Bronson, Richard, Cattanach, Bruce, Daniel, Joseph C., Dawes, Edwin A., Ferguson-Smith, Malcolm, Gardner, Richard, Griffin, Dave, Hunter, R. H. F., Johnson, Martin, Jones, Howard, Lunenfeld, Bruno, Mittwoch, Ursula, Moor, Robert, Rankin, Barbara, Schally, Andrew V., Sharpe, David J., Simpson, David, Yanagimachi, Ryuzo Yana, Alexandre, Henri, Bhargava, Pushpa M., Dexter, Alan, Diedrich, Klaus, Emperaire, Jean-Claude, Findlay, Alan, Fishel, Simon, Fox, Norma Lynn, Goddard, Hester, Gomel, Victor, Gore-Langton, Robert E., Gosden, Roger, Iritani, A., Koskimies, Aarne I., Macdonald, Grace, Menezo, Yves, Mettler, Liselotte, Monk, Marilyn, Mori, Takahide, Mortimer, David, Papaioannou, Virginia E., Racowsky, Catherine, Surani, Azim, Trounson, Alan, Blerkom, Jonathan, Vincent, Paul, Walters, Eurof, Webster, John, Williams, Peter, Aboulghar, M., Barri, Pedro N., Benagiano, Giuseppe, Blackwell, Caroline, Bolton, Virginia N., Brinsden, Peter R., Bustillo, Maria, Coulam, Carolyn, Chaouat, Gerard, Crosignani, Piergiorgio, Gardner, David, Gianaroli, Luca, Hamberger, Lars, Hartshorne, Geraldine, Hollands, Peter, Howles, Colin, Illmensee, Karl, Jauniaux, Eric, Kini, Dee, Lee, Sammy, Lees, Martin, Leese, Henry, Mathews, Thomas, Moate, Elaine, Nygren, Karl, Colin Ockleford, Palermo, Gianpiero D., Pandiyan, N., Rizk, Botros, Rosenwaks, Zev, Sallam, Hassan, Sathananthan, A. Henry, Saunders, Douglas M., Simpson, Joe Leigh, Sunde, Arne, Tan, Seang Lin, Ulloa-Aguirre, Alfredo, Gosden, Lucinda Veeck, Veiga, Anna, Albertini, David F., Alikani, Mina, Balaban, Basak, Thornhill, Alan, Beard, Helen K., Ben-Shlomo, Izhar, Borini, Andrea, Carrell, Douglas, Jonge, Christopher, Eichenlaub-Ritter, Ursula, Fleming, Steven, Geber, Selmo, Gerris, Jan, Golombok, Susan, Leather, Dame Suzi, Nagy, Zsolt Peter, Nielsen, H. Ingolf, Oehninger, Sergio, Olivennes, Francois, Patrizio, Pasquale, Paulson, Richard J., Polak Fried, Ester, Pool, Thomas B., Risquez, Francisco, Sauer, Mark V., Sciarra, John J., Basuray, Rita, Boiso, Irene, Bose, Chinmoy K., Cryan, Bob, Falconer, Anthony, Hansis, Christoph, Kahraman, Semra, Ko, Minoru S. H., Korsak, Vladislav, Loeffler, Frank, Ludwig, Michael, Magli, M. Cristina, Robertson, John A., Roche, Lady Alexandra, Thornhill, A., Wallberg-Henriksson, Harriet, Woo, George, and Ivf, Canada

4. Salute to a giant ... Robert Geoffrey Edwards

Author

Ahuja, Kamal, Bennett, Fiona, Cohen, Jacques, Edwards, Ruth, Pritchard, Huw, Silver, Ann, Sirlin, Julio, Slee, John, Abse, Dannie, Ashwood-Smith, M. J., Bavister, Barry, Bedford, J. Michael, Beier, Henning M., Bronson, Richard, Cattanach, Bruce, Daniel, Joseph C., Dawes, Edwin A., Ferguson-Smith, Malcolm, Gardner, Richard, Griffin, Dave, Hunter, R. H. F., Johnson, Martin, Jones, Howard, Lunenfeld, Bruno, Mittwoch, Ursula, Moor, Robert, Rankin, Barbara, Schally, Andrew V., Sharpe, David J., Simpson, David, Yanagimachi, Ryuzo Yana, Alexandre, Henri, Bhargava, Pushpa M., Dexter, Alan, Diedrich, Klaus, Emperaire, Jean-Claude, Findlay, Alan, Fishel, Simon, Fox, Norma Lynn, Goddard, Hester, Gomel, Victor, Gore-Langton, Robert E., Gosden, Roger, Iritani, A., Koskimies, Aarne I., Macdonald, Grace, Menezo, Yves, Mettler, Liselotte, Monk, Marilyn, Mori, Takahide, Mortimer, David, Papaioannou, Virginia E., Racowsky, Catherine, Surani, Azim, Trounson, Alan, Blerkom, Jonathan, Vincent, Paul, Walters, Eurof, Webster, John, Williams, Peter, Aboulghar, M., Barri, Pedro N., Benagiano, Giuseppe, Blackwell, Caroline, Bolton, Virginia N., Brinsden, Peter R., Bustillo, Maria, Coulam, Carolyn, Chaouat, Gerard, Crosignani, Piergiorgio, Gardner, David, Gianaroli, Luca, Hamberger, Lars, Hartshorne, Geraldine, Hollands, Peter, Howles, Colin, Illmensee, Karl, Jauniaux, Eric, Kini, Dee, Lee, Sammy, Lees, Martin, Leese, Henry, Mathews, Thomas, Moate, Elaine, Nygren, Karl, Ockleford, Colin, Palermo, Gianpiero D., Pandiyan, N., Rizk, Botros, Rosenwaks, Zev, Hossam El-Din Sallam, Sathananthan, A. Henry, Saunders, Douglas M., Simpson, Joe Leigh, Sunde, Arne, Tan, Seang Lin, Ulloa-Aguirre, Alfredo, Gosden, Lucinda Veeck, Veiga, Anna, Albertini, David F., Alikani, Mina, Balaban, Basak, Thornhill, Alan, Beard, Helen K., Ben-Shlomo, Izhar, Borini, Andrea, Carrell, Douglas, Jonge, Christopher, Eichenlaub-Ritter, Ursula, Fleming, Steven, Geber, Selmo, Gerris, Jan, Golombok, Susan, Leather, Dame Suzi, Nagy, Zsolt Peter, Nielsen, H. Ingolf, Oehninger, Sergio, Olivennes, Francois, Patrizio, Pasquale, Paulson, Richard J., Polak Fried, Ester, Pool, Thomas B., Risquez, Francisco, Sauer, Mark V., Sciarra, John J., Basuray, Rita, Boiso, Irene, Bose, Chinmoy K., Cryan, Bob, Falconer, Anthony, Hansis, Christoph, Kahraman, Semra, Ko, Minoru S. H., Korsak, Vladislav, Loeffler, Frank, Ludwig, Michael, Magli, M. Cristina, Robertson, John A., Roche, Lady Alexandra, Thornhill, A., Wallberg-Henriksson, Harriet, and Woo, George

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