Frequency and impact of obstetric complications prior and subsequent to unexplained secondary recurrent miscarriage
Abstract
The chance of a live birth after a diagnosis of secondary recurrent miscarriage (SRM) is reduced in patients who, prior to the miscarriages, gave birth to a boy and carry HLA class II alleles that efficiently present male-specific (H-Y) antigens to the immune system. Information about obstetric complications in births prior and subsequent to the SRM diagnosis is limited. The relations between maternal carriage of H-Y-restricting HLA, fetal sex, obstetric complications and prognosis are unknown. Women with unexplained SRM referred to the Danish Recurrent Miscarriage Clinic between 1986 and 2006 (n = 358) were included; 213 gave birth after the diagnosis. Controls, retrieved from the Danish National Birth Registry, were all women with singleton birth of parity 0, 1982–2005 (n = 608 068) and parity 1, 1986–2008 (n = 510 264). Cross-linkage to the National Discharge Registry identified birth complication diagnoses related to the relevant births among patients and controls. The sex ratio was 1.49 in births prior to SRM and 0.76 in birth after SRM (P < 0.0001). For SRM patients with only late miscarriages (>10 weeks gestation), the corresponding sex ratios were 2.31 and 0.21. Compared with the control groups, obstetric complications were more frequent both before (39% versus 24% P ≤ 0.01) and after (19% versus 14%, P = 0.01) SRM diagnosis. Births were more frequently complicated when the child was a boy (44% versus 31%, P = 0.02) before and a girl (24% versus 13%, P = 0.04) after SRM diagnosis. SRM patients with H-Y-restricting HLA class II alleles and a firstborn boy gave birth to children who weighed on average 381 g less (P = 0.006) and were born 0.9 weeks earlier (P = 0.06) and their births had more obstetric complications (P = 0.05) than patients with the same HLA alleles but a firstborn girl. Obstetric complications, sex ratios in births prior and subsequent to SRM and maternal carriage of H-Y-restricting HLA class II alleles are associated parameters. Immune responses against fetal H-Y antigens initiated in the pregnancy prior to the SRM may play a causal role in SRM.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Exposure to air pollution is associated with an increased risk of miscarriage (OR 1.51; 95% CI 1.33-1.69) in Beijing.
“A large study assessed the effect of exposure to air pollution on miscarriage rates in Beijing, demonstrating a strong relationship with miscarriage (OR 1·51; 95% CI 1·33-1·69) . 91”
From Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss (2021) · cites this paper as [91]
The Complication variables and Obstetric and neonatal complications sections describe Danish registry data on births before and after secondary recurrent miscarriage, not air-pollution exposure in Beijing. Searches for “air pollution Beijing miscarriage” and “1.51 1.33 1.69” found no passage reporting the claimed association or odds ratio. (LLM, conf=0.77)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Steinman, R. M., Hawiger, D., & Nussenzweig, M. C. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141040 · Cited by 3,124 · see citing works
THE JOURNAL OF REPRODUCTIVE MEDICINE
Reddy, D. M., & Wasserman, S. A. (1999) · AJN American Journal of Nursing · doi:10.1097/00000446-199901000-00024 · Cited by 2,483 · see citing works
A New and Improved Population-Based Canadian Reference for Birth Weight for Gestational Age
Kramer, M. S., Platt, R. W., Wen, S. W., Joseph, K. S., Allen, A. C., Abrahamowicz, M., Blondel, B., Bréart, G., & Bréart, G. (2001) · PEDIATRICS · doi:10.1542/peds.108.2.e35 · Cited by 1,526 · see citing works
Altman, D. G., Carroli, G., Duley, L., Farrell, B., Moodley, J., Neilson, J., & Smith, D. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08778-0 · Cited by 1,488 · see citing works
Risk of pre-eclampsia in first and subsequent pregnancies: prospective cohort study
Hernández–Dı́az, S., Toh, S., & Cnattingius, S. (2009) · BMJ · doi:10.1136/bmj.b2255 · Cited by 568 · see citing works
Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study
Stephenson, M. D. (2002) · Human Reproduction · doi:10.1093/humrep/17.2.446 · Cited by 522 · see citing works
Girardi, G., Yarilin, D. A., Thurman, J. M., Holers, V. M., & Salmon, J. E. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061022 · Cited by 507 · see citing works
Determinant spreading and the dynamics of the autoimmune T-cell repertoire
Lehmann, P., Sercarz, E. E., Forsthuber, T. G., Dayan, C. M., & Gammon, G. M. (1993) · Immunology Today · doi:10.1016/0167-5699(93)90163-f · Cited by 461 · see citing works
Germain, S., Sacks, G. P., Soorana, S. R., Sargent, I. L., & Redman, C. W. G. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5949 · Cited by 457 · see citing works
Does fetal sex affect pregnancy outcome?
Renzo, G. C. D., Rosati, A., Sarti, R. D., Cruciani, L., & Cutuli, A. M. (2007) · Gender Medicine · doi:10.1016/s1550-8579(07)80004-0 · Cited by 447 · see citing works
Goswami, D., Tannetta, D., Magee, L. A., Fuchisawa, A., Redman, C. W. G., Sargent, I. L., & von Dadelszen, P. (2005) · Placenta · doi:10.1016/j.placenta.2004.11.007 · Cited by 402 · see citing works
Zhu, W. X., Li, L., & Hesketh, T. M. (2009) · BMJ · doi:10.1136/bmj.b1211 · Cited by 378 · see citing works
Apoptosis and its role in the trophoblast
Huppertz, B., Kadyrov, M., & Kingdom, J. C. (2006) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2005.07.039 · Cited by 343 · see citing works
Evidence-based investigations and treatments of recurrent pregnancy loss
Christiansen, O. B., Andersen, A. N., Bosch, E., Daya, S., Delves, P. J., Hviid, T. V. F., Kutteh, W. H., Laird, S. M., Li, T. C., & van der Ven, K. (2005) · Fertility and Sterility · doi:10.1016/j.fertnstert.2004.12.018 · Cited by 303 · see citing works
Self-citationKlemmensen, A., Olsen, S. F., Østerdal, M. L., & Tabor, A. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm139 · Cited by 228 · see citing works
Etiologic determinants of abruptio placentae
KRAMER, M., USHER, R., POLLACK, R., BOYD, M., & USHER, S. (1997) · Obstetrics & Gynecology · doi:10.1016/s0029-7844(96)00478-4 · Cited by 212 · see citing works
Resnik, R. R. (2003) · Obstetrics and Gynecology · doi:10.1097/00006250-200310000-00002 · Cited by 201 · see citing works
Verdijk, R. M., Kloosterman, A., Pool, J., van der Keur, M., Naipal, A. M. I. H., van Halteren, A. G. S., Brand, A., Mutis, T., & Goulmy, E. (2003) · Blood · doi:10.1182/blood-2003-05-1625 · Cited by 198 · see citing works
H-Y Male Antigen: Detection on Eight-Cell Mouse Embryos
Krco, C. J., & GOLDBERG, E. H. (1976) · Science · doi:10.1126/science.959826 · Cited by 179 · see citing works
Zorn, E., Miklos, D. B., Floyd, B. H., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031560 · Cited by 175 · see citing works
The Human UTY Gene Encodes a Novel HLA-B8-Restricted H-Y Antigen
Warren, E. H., Gavin, M. A., Simpson, E., Chandler, P., Page, D. C., Distèche, C. M., Stankey, K. A., Greenberg, P. D., & Riddell, S. R. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.5.2807 · Cited by 174 · see citing works
Sex Ratio and Twinning in Women With Hyperemesis or Pre-eclampsia
Basso, O., & Olsen, J. (2001) · Epidemiology · doi:10.1097/00001648-200111000-00026 · Cited by 165 · see citing works
Hansen, D., Møller, H., & Olsen, J. (1999) · BMJ · doi:10.1136/bmj.319.7209.548 · Cited by 159 · see citing works
Vogt, M. H. J., van den Muijsenberg, J. W., Goulmy, E., Spierings, E., Kluck, P., Kester, M. G. D., van Soest, R. A., Drijfhout, J. W., Willemze, R., & Falkenburg, J. H. F. (2002) · Blood · doi:10.1182/blood.v99.8.3027 · Cited by 157 · see citing works
Gratwohl, A. A., Hermans, J., Niederwieser, D. W., et al. (2001) · The Hematology Journal · doi:10.1038/sj.thj.6200117 · Cited by 134 · see citing works
Predicting recurring miscarriage: what is important?
Quenby, S. M., & Farquharson, R. G. (1993) · PubMed · Cited by 132 · see citing works
Spierings, E., Vermeulen, C., Vogt, M. H. J., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14191-8 · Cited by 126 · see citing works
Obstetric and neonatal outcome in women with a history of recurrent miscarriage: a cohort study
Jivraj, S., Anstie, B., Cheong, Y. C., Fairlie, F., Laird, S. M., & Li, T. C. (2001) · Human Reproduction · doi:10.1093/humrep/16.1.102 · Cited by 126 · see citing works
Obstetric outcomes subsequent to intrauterine death in the first pregnancy
Black, M. E., Shetty, A., & Bhattacharya, S. (2007) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2007.01562.x · Cited by 114 · see citing works
Tulppala, M., Palosuo, T., Ramsay, T., Miettinen, A., Salonen, R., & Ylikorkala, O. (1993) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a138137 · Cited by 112 · see citing works
Recurring Complications in Second Pregnancy
Lykke, J. A., Paidas, M. J., & Langhoff‐Roos, J. (2009) · Obstetrics and Gynecology · doi:10.1097/aog.0b013e3181a66f2d · Cited by 106 · see citing works
Khashan, A. S., Henriksen, T. B., Mortensen, P. B., et al. (2009) · Human Reproduction · doi:10.1093/humrep/dep409 · Cited by 104 · see citing works
Pregnancy outcome following recurrent spontaneous abortions
Sheiner, E., Levy, A., Katz, M. E., et al. (2004) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2004.06.015 · Cited by 76 · see citing works
Nielsen, H. S., Steffensen, R., Varming, K., van Halteren, A. G. S., Spierings, E., Ryder, L. P., Goulmy, E., & Christiansen, O. B. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp077 · Cited by 74 · see citing works
Self-citationReginald, P. W., Beard, R. W., Chapple, J., et al. (1987) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1987.tb03168.x · Cited by 74 · see citing works
The Changing Maternal “Self” Hypothesis: A Mechanism for Maternal Tolerance of the Fetus
Waldorf, K. M. A., Yan, Z., Stevens, A. M., & Nelson, J. L. (2006) · Placenta · doi:10.1016/j.placenta.2006.07.003 · Cited by 66 · see citing works
Impact of the sex of first child on the prognosis in secondary recurrent miscarriage
Christiansen, O. B., Pedersen, B., Nielsen, H. S., & Andersen, A. N. (2004) · Human Reproduction · doi:10.1093/humrep/deh516 · Cited by 58 · see citing works
Self-citationKatz, V. L., & Kuller, J. A. (1994) · American Journal of Perinatology · doi:10.1055/s-2007-994603 · Cited by 56 · see citing works
Ott, P. A., Dittrich, M. T., Herzog, B. A., et al. (2004) · Journal of Clinical Immunology · doi:10.1023/b:joci.0000029120.77824.41 · Cited by 54 · see citing works
Nielsen, H. S., Andersen, A. N., Kolte, A. M., & Christiansen, O. B. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.04.029 · Cited by 50 · see citing works
Self-citationOccurrence of placental abruption in relatives
Rasmussen, S., & Irgens, L. (2009) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2008.02064.x · Cited by 38 · see citing works
Nielsen, H. S., & Christiansen, O. B. (2005) · Human Reproduction · doi:10.1093/humrep/deh790 · Cited by 36 · see citing works
Self-citationYang, C. J., STONE, P. R., & Stewart, A. W. (2006) · Australian and New Zealand Journal of Obstetrics and Gynaecology · doi:10.1111/j.1479-828x.2006.00599.x · Cited by 34 · see citing works
Recurring Complications in Second Pregnancy
Lykke, J. A., Paidas, M. J., & Langhoff‐Roos, J. (2010) · Obstetric Anesthesia Digest · doi:10.1097/01.aoa.0000370512.23856.74 · Cited by 27 · see citing works
Obstetric outcome in women after multiple spontaneous abortions.
Hughes, N., Ef, H., & Tulandi, T. (1991) · PubMed · Cited by 27 · see citing works
Gerber, S., Vardhana, S. A., Meagher‐Villemure, K., Vial, Y., Hohlfeld, P., & Witkin, S. S. (2005) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2005.02.112 · Cited by 24 · see citing works
Weintraub, A. Y., Sheiner, E., Bashiri, A., Shoham‐Vardi, I., & Mazor, M. (2004) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-004-0640-z · Cited by 24 · see citing works
Khashan, A. S., Mortensen, P. B., McNamee, R., et al. (2009) · Human Reproduction · doi:10.1093/humrep/dep082 · Cited by 18 · see citing works
Psychological aspects of spontaneous and recurrent abortion
Bagchi, D., & Friedman, T. (1999) · Current Obstetrics and Gynaecology · doi:10.1016/s0957-5847(99)90068-9 · Cited by 12 · see citing works
Study of the birthweight of parents experiencing unexplained recurrent miscarriages
CHRISTIANSEN, O. B., MATHIESEN, O., LAURITSEN, J. G., & GRUNNET, N. (1992) · BJOG: An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1992.tb13759.x · Cited by 12 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Quenby, S., Gallos, I. D., Dhillon-Smith, R. K., Podesek, M., Stephenson, M. D., Fisher, J., Brosens, J. J., Brewin, J., Ramhorst, R., Lucas, E. S., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00682-6 · Cited by 1,560 · see citing works
Self-citationInvestigation of systemic inflammatory response in first trimester pregnancy failure
Calleja-Agius, J., Jauniaux, E., Pizzey, A. R., & Muttukrishna, S. (2012) · Human Reproduction · doi:10.1093/humrep/der402 · Cited by 119 · see citing works
Shiozaki, A., Matsuda, Y., Satoh, S., & Saito, S. (2013) · Journal of Obstetrics and Gynaecology Research · doi:10.1111/j.1447-0756.2012.01990.x · Cited by 63 · see citing works
Katano, K., Suzuki, S., Ozaki, Y., Suzumori, N., Kitaori, T., & Sugiura-Ogasawara, M. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.07.1996 · Cited by 63 · see citing works
Sugiura‐Ogasawara, M., Ebara, T., Yamada, Y., Shoji, N., Matsuki, T., Kano, H., Kurihara, T., Omori, T., Tomizawa, M., Miyata, M., et al. (2019) · American Journal of Reproductive Immunology · doi:10.1111/aji.13072 · Cited by 51 · see citing works
- Authors
- Nielsen, H. S., Steffensen, R., Lund, M., Egestad, L., Mortensen, L. H., Andersen, A. M. N., Lidegaard, O., & Christiansen, O. B.
- Affiliations
- Copenhagen University Hospital (DK)
- Aalborg University Hospital (DK)
- University of Southern Denmark (DK)
- Corresponding author
- Nielsen, H. S.
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-04-14
- Volume
- 25
- Issue
- 6
- Pages
- 1543-1552
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2103637598
- Cited by
- 61
- References
- 50
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 7 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 4 · 2012: 4
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- CSL Behring
- Rigshospitalet
- Det Obelske Familiefond
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Keywords
- unexplained recurrent spontaneous abortion, pregnancy complications, fetal sex ratio, late miscarriage
- MeSH terms
- Abortion, Habitual, Alleles, Denmark, Female, H-Y Antigen, HLA Antigens, Humans, Infant, Newborn, Male, Pregnancy, Pregnancy Complications, Registries, Risk Factors, Statistics, Nonparametric, Live Birth, Histocompatibility, Maternal-Fetal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
