Modern view of the causes of antenatal fetal death

Abstract

About two million cases of prenatal fetal death are recorded annually, that is, a stillborn baby is born every 16 seconds. However, even such impressive data does not reflect the full scale of the problem. The WHO data does not include stillbirth rates at 22–28 weeks, which some studies estimate would increase the rate by about 40%. The difference in stillbirth rates in developed and developing countries indicates the quality of medical care and, as a result, the country’s medical system. According to the Federal State Statistics Service, the stillbirth rate in the Russian Federation accounts for a large share of perinatal loss (79%) and does not have a downward trend. Besides, there is currently no unified classification of the causes of prenatal fetal death, which complicates the analysis of stillbirth cases and possible reserves for their reduction. It is noteworthy that the proportion of cases with an unknown cause of perinatal mortality is growing (3.1% in 2019 and 4.7% in 2020). Despite the fact that the rate of unexplained causes of antenatal fetal death in the Russian Federation is almost three times lower than abroad, the large proportion of causes associated with fetal asphyxia deprives these data of specificity. Against the backdrop of the demographic crisis in the Russian Federation (the birth rate for 2022 was 1.4), identifying risk factors for antenatal fetal death is especially acute, since this underlies the creation of preventive measures to reduce the risk of adverse obstetric outcomes.

Keywords

antenatal fetal death / stillbirth / risk factors / pregnancy

References

[1] Strizhakov AN, Ignatko IV, Rodionova AM. Antenatal fetal death: a textbook Moscow: GEOTAR Media; 2023. EDN: TWKRZN

[2] Стрижаков А.Н., Игнатко И.В., Родионова А.М. Антенатальная гибель плода: учебное пособие. Москва: ГЭОТАР-Медиа, 2023. EDN: TWKRZN doi: 10.33029/9704-7804-2-AGP-2023-1-80

[3] Ivanov II, Lyashenko EN, Kosolapova NV, et al. Antenatal fetal death: unresolved issues. TMBV. 2020;23(1):37–41. EDN: SENXEX

[4] Иванов И.И., Ляшенко Е.Н., Косолапова Н.В., и др. Антенатальная гибель плода: нерешенные вопросы // ТМБВ. 2020. Т. 23, № 1. С. 37–41. EDN: SENXEX doi: 10.37279/2070-8092-2020-23-1-37-41

[5] UNICEF Data [Internet]. Stillbirths and stillbirth rates. 2023 [cited 2024 Oct 5]. Available from https://data.unicef.org/topic/child-survival/stillbirths/.

[6] UNICEF Data [Электронный ресурс]. Stillbirths and stillbirth rates. 2023. Режим доступа: https://data.unicef.org/topic/child-survival/stillbirths/. Дата обращения: 05.10.2024.

[7] Flenady V, Koopmans L, Middleton P, et al. Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis. Lancet. 2011;377(9774):1331–1340. doi: 10.1016/S0140-6736(10)62233-7

[8] Flenady V., Koopmans L., Middleton P., et al. Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis // Lancet. 2011. Vol. 377, N 9774. P. 1331–1340. doi: 10.1016/S0140-6736(10)62233-7

[9] Zhakanova LK, Espayeva RN, Seralieva ZhE, et al. Analysis of perinatal mortality indicators in Almaty for 2018–2019. Bulletin of the AGIUV. 2020;(2). (In Russ.)

[10] Жаканова Л.К., Еспаева Р.Н., Сералиева Ж.Е., и др. Анализ показателей перинатальной смертности по г. Алматы за 2018–2019 гг. // Вестник АГИУВ. 2020. № 2. С. 163–166.

[11] Saccone G, Gragnano E, Ilardi B, et al. Maternal and perinatal complications according to maternal age: a systematic review and meta-analysis. Int J Gynaecol Obstet. 2022;159(1):43–55. doi: 10.1002/ijgo.14100

[12] Saccone G., Gragnano E., Ilardi B., et al. Maternal and perinatal complications according to maternal age: a systematic review and meta-analysis // Int J Gynaecol Obstet. 2022. Vol. 159, N 1. P. 43–55. doi: 10.1002/ijgo.14100

[13] Shakeel A, Kamal A, Ijaz M, et al. Trends and risk factors of stillbirth among women of reproductive age in Pakistan: a multivariate decomposition analysis. Front Public Health. 2023 Feb 23;11. doi: 10.3389/fpubh.2023.1050136

[14] Shakeel A., Kamal A., Ijaz M., et al. Trends and risk factors of stillbirth among women of reproductive age in Pakistan: a multivariate decomposition analysis // Front Public Health. 2023. Vol. 11. doi: 10.3389/fpubh.2023.1050136

[15] Glick I, Kadish E, Rottenstreich M. Management of pregnancy in women of advanced maternal age: improving outcomes for mother and baby. Int J Womens Health. 2021;13:751–759. doi: 10.2147/IJWH.S283216.

[16] Glick I., Kadish E., Rottenstreich M., et al. Management of pregnancy in women of advanced maternal age: improving outcomes for mother and baby // Int J Womens Health. 2021. Vol. 13. P. 751–759. doi: 10.2147/IJWH.S283216

[17] Hedstrom AB, Choo EM, Ronen K, et al. Risk factors for stillbirth and neonatal mortality among participants in Mobile WACh NEO pilot, a two-way SMS communication program in Kenya. PLOS Glob Public Health. 2022;2(7). doi: 10.1371/journal.pgph.0000812

[18] Hedstrom A.B., Choo E.M., Ronen K., et al. Risk factors for stillbirth and neonatal mortality among participants in Mobile WACh NEO pilot, a two-way SMS communication program in Kenya // PLOS Glob Public Health. 2022. Vol. 2, N 7. P. 812–818. doi: 10.1371/journal.pgph.0000812

[19] Escañuela Sánchez T, Meaney S, O’Donoghue K. Modifiable risk factors for stillbirth: a literature review. Midwifery. 2019;79. doi: 10.1016/j.midw.2019.102539

[20] Escañuela Sánchez T., Meaney S., O’Donoghue K. Modifiable risk factors for stillbirth: a literature review // Midwifery. 2019 Vol. 79. doi: 10.1016/j.midw.2019.102539

[21] Shinohara S, Shinohara R, Kojima R, et al. Obesity as a potential risk factor for stillbirth: the Japan environment and children’s study. Prev Med Rep. 2023;35. doi: 10.1016/j.pmedr.2023.102391

[22] Shinohara S., Shinohara R., Kojima R., et al. Obesity as a potential risk factor for stillbirth: the Japan environment and children’s study // Prev Med Rep. 2023. Vol. 35. doi: 10.1016/j.pmedr.2023.102391

[23] Pritchard NL, Hiscock R, Walker SP, et al. Defining poor growth and stillbirth risk in pregnancy for infants of mothers with overweight and obesity. Am J Obstet Gynecol. 2023;229(1):59.e1–59.e12. doi: 10.1016/j.ajog.2022.12.322

[24] Pritchard N.L., Hiscock R., Walker S.P., et al. Defining poor growth and stillbirth risk in pregnancy for infants of mothers with overweight and obesity // Am J Obstet Gynecol. 2023. Vol. 229, N 1. P. 59–112. doi: 10.1016/j.ajog.2022.12.322

[25] Ikedionwu CA, Dongarwar D, Yusuf KK, et al. Pre-pregnancy maternal obesity, macrosomia, and risk of stillbirth: a population-based study. Eur J Obstet Gynecol Reprod Biol. 2020;252:1–6. doi: 10.1016/j.ejogrb.2020.06.004

[26] Ikedionwu C.A., Dongarwar D., Yusuf K.K., et al. Pre-pregnancy maternal obesity, macrosomia, and risk of stillbirth: a population-based study // Eur J Obstet Gynecol Reprod Biol. 2020. Vol. 252. P. 1–6. doi: 10.1016/j.ejogrb.2020.06.004.

[27] Mahomed K, Chan G, Norton M. Obesity and the risk of stillbirth — A reappraisal — a retrospective cohort study. Eur J Obstet Gynecol Reprod Biol. 2020;255:25–28. doi: 10.1016/j.ejogrb.2020.09.044

[28] Mahomed K., Chan G., Norton M. Obesity and the risk of stillbirth — a reappraisal — a retrospective cohort study // Eur J Obstet Gynecol Reprod Biol. 2020. Vol. 255. P. 25–28. doi: 10.1016/j.ejogrb.2020.09.044

[29] Odendaal H, Dukes KA, Elliott AJ, et al. Association of prenatal exposure to maternal drinking and smoking with the risk of stillbirth. JAMA Netw Open. 2021;4(8). doi: 10.1001/jamanetworkopen.2021.21726

[30] Odendaal H., Dukes K.A., Elliott A.J., et al. Association of prenatal exposure to maternal drinking and smoking with the risk of stillbirth // JAMA Netw Open. 2021. Vol. 4, N 8. doi: 10.1001/jamanetworkopen.2021.21726

[31] Qu Y, Chen S, Pan H, et al. Exposure to tobacco smoke and stillbirth: a national prospective cohort study in rural China. J Epidemiol Community Health. 2020;74(4):315–320. doi: 10.1136/jech-2019-213290

[32] Qu Y., Chen S., Pan H., et al. Exposure to tobacco smoke and stillbirth: a national prospective cohort study in rural China // J Epidemiol Community Health. 2020. Vol. 74, N 4. P. 315–320. doi: 10.1136/jech-2019-213290

[33] Hoch D, Majali-Martinez A, Bankoglu EE, et al. Maternal smoking in the first trimester and its consequence on the early placenta. Lab Invest. 2023;103(5). doi: 10.1016/j.labinv.2022.100059

[34] Hoch D., Majali-Martinez A., Bankoglu E.E., et al. Maternal smoking in the first trimester and its consequence on the early placenta // Lab Invest. 2023. Vol. 103, N 5. doi: 10.1016/j.labinv.2022.100059

[35] Doherty E, Wiggers J, Wolfenden L, et al. Antenatal care for alcohol consumption during pregnancy: pregnant women’s reported receipt of care and associated characteristics. BMC Pregnancy Childbirth. 2019;19(1):299. doi: 10.1186/s12884-019-2436-y

[36] Doherty E., Wiggers J., Wolfenden L., et al. Antenatal care for alcohol consumption during pregnancy: pregnant women’s reported receipt of care and associated characteristics // BMC Pregnancy Childbirth. 2019. Vol. 19, N 1. P. 299. doi: 10.1186/s12884-019-2436-y

[37] Lu Q, Zhang X, Wang Y, et al. Sleep disturbances during pregnancy and adverse maternal and fetal outcomes: a systematic review and meta-analysis. Sleep Med Rev. 2021;58. doi: 10.1016/j.smrv.2021.101436

[38] Lu Q., Zhang X., Wang Y., et al. Sleep disturbances during pregnancy and adverse maternal and fetal outcomes: a systematic review and meta-analysis // Sleep Med Rev. 2021. Vol. 58. doi: 10.1016/j.smrv.2021.101436.

[39] Escañuela Sánchez T, O’Donoghue K, Byrne M, et al. A systematic review of behaviour change techniques used in the context of stillbirth prevention. Women Birth. 2023;36(5):e495–e508. doi: 10.1016/j.wombi.2023.05.002

[40] Escañuela Sánchez T., O’Donoghue K., Byrne M., et al. A systematic review of behaviour change techniques used in the context of stillbirth prevention // Women Birth. 2023. Vol. 36, N 5. P. e495–e508. doi: 10.1016/j.wombi.2023.05.002

[41] WHO recommendations on antenatal care for a positive pregnancy experience. Geneva; 2017.

[42] Рекомендации ВОЗ по оказанию дородовой помощи для формирования положительного опыта беременности. Женева: Всемирная организация здравоохранения, 2017.

[43] Mukherjee A, Di Stefano L, Blencowe H, et al. Determinants of stillbirths in sub-Saharan Africa: a systematic review. BJOG. 2024;131(2):140–150. doi: 10.1111/1471-0528.17562

[44] Mukherjee A., Di Stefano L., Blencowe H., et al. Determinants of stillbirths in sub-Saharan Africa: a systematic review // BJOG. 2024. Vol. 131, N 2. P. 140–150. doi: 10.1111/1471-0528.17562

[45] Kumar J, Saini SS, Kumar P. Care during labour, childbirth, and immediate newborn care in India: a review. Indian J Pediatr. 2023;90(1):20–28. doi: 10.1007/s12098-023-04721-7

[46] Kumar J., Saini S.S., Kumar P. Care during labour, childbirth, and immediate newborn care in India: a review // Indian J Pediatr. 2023. Vol. 90, N 1. P. 20–28. doi: 10.1007/s12098-023-04721-7

[47] Heemelaar S, Callard B, Shikwambi H, et al. Confidential enquiry into maternal deaths in Namibia, 2018–2019: a local approach to strengthen the review process and a description of review findings and recommendations. Matern Child Health J. 2023;27(12):2165–2174. doi: 10.1007/s10995-023-03771-9

[48] Heemelaar S., Callard B., Shikwambi H., et al. Confidential enquiry into maternal deaths in Namibia, 2018–2019: a local approach to strengthen the review process and a description of review findings and recommendations // Matern Child Health J. 2023. Vol. 27, N 12. P. 2165–2174. doi: 10.1007/s10995-023-03771-9

[49] Dolanc Merc M, Peterlin B, Lovrecic L. The genetic approach to stillbirth: a systematic review. Prenat Diagn. 2023;43(9):1220–1228. doi: 10.1002/pd.6354

[50] Dolanc Merc M., Peterlin B., Lovrecic L. The genetic approach to stillbirth: a systematic review // Prenat Diagn. 2023. Vol. 43, N 9. P. 1220–1228. doi: 10.1002/pd.6354

[51] Okoth K, Chandan JS, Marshall T, et al. Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review. BMJ. 2020;371. doi: 10.1136/bmj.m3502

[52] Okoth K., Chandan J.S., Marshall T., et al. Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review // BMJ. 2020. Vol. 7, N 371. P. 3502. doi: 10.1136/bmj.m3502

[53] Malaza N, Masete M, Adam S, et al. A systematic review to compare adverse pregnancy outcomes in women with pregestational diabetes and gestational diabetes. Int J Environ Res Public Health. 2022;19(17). doi: 10.3390/ijerph191710846

[54] Malaza N., Masete M., Adam S., et al. A systematic review to compare adverse pregnancy outcomes in women with pregestational diabetes and gestational diabetes // Int J Environ Res Public Health. 2022. Vol. 19, N 17. doi: 10.3390/ijerph191710846

[55] Chappell LC, Cluver CA, Kingdom J, et al. Pre-eclampsia. Lancet. 2021;398(10297):341–354. doi: 10.1016/S0140-6736(20)32335-7

[56] Chappell L.C., Cluver C.A., Kingdom J., et al. Pre-eclampsia // Lancet. 2021. Vol. 398, N 10297. P. 341–354. doi: 10.1016/S0140-6736(20)32335-7

[57] Brandt JS, Ananth CV. Placental abruption at near-term and term gestations: pathophysiology, epidemiology, diagnosis, and management. Am J Obstet Gynecol. 2023;228(5):1313–1329. doi: 10.1016/j.ajog.2022.06.059

[58] Brandt J.S., Ananth C.V. Placental abruption at near-term and term gestations: pathophysiology, epidemiology, diagnosis, and management // Am J Obstet Gynecol. 2023. Vol. 228, N 5. P. 1313–1329. doi: 10.1016/j.ajog.2022.06.059

[59] Jenabi E, Salimi Z, Ayubi E, et al. The environmental risk factors prior to conception associated with placental abruption: an umbrella review. Syst Rev. 2022;11(1):55. doi: 10.1186/s13643-022-01915-6

[60] Jenabi E., Salimi Z., Ayubi E., et al. The environmental risk factors prior to conception associated with placental abruption: an umbrella review // Syst Rev. 2022. Vol. 11, N 1. P. 55. doi: 10.1186/s13643-022-01915-6

[61] Lemieux P, Benham JL, Donovan LE, et al. The association between gestational diabetes and stillbirth: a systematic review and meta-analysis. Diabetologia. 2022;65(1):37–54. doi: 10.1007/s00125-021-05579-0

[62] Lemieux P., Benham J.L., Donovan L.E., et al. The association between gestational diabetes and stillbirth: a systematic review and meta-analysis // Diabetologia. 2022. Vol. 65, N 1. P. 37–54. doi: 10.1007/s00125-021-05579-0

[63] Singh M, Wambua S, Lee SI, et al. Autoimmune diseases and adverse pregnancy outcomes: an umbrella review. Lancet. 2023;402(1):84. doi: 10.1016/S0140-6736(23)02128-1

[64] Singh M., Wambua S., Lee S.I., et al. Autoimmune diseases and adverse pregnancy outcomes: an umbrella review // Lancet. 2023. Vol. 402, N 1. P. 84. doi: 10.1016/S0140-6736(23)02128-1

[65] Wilkins-Haug L. Genetic innovations and our understanding of stillbirth. Hum Genet. 2020;139(9):1161–1172. doi: 10.1007/s00439-020-02146-2

[66] Wilkins-Haug L. Genetic innovations and our understanding of stillbirth // Hum Genet. 2020. Vol. 139, N 9. P. 1161–1172. doi: 10.1007/s00439-020-02146-2

[67] Hays T, Wapner RJ. Genetic testing for unexplained perinatal disorders. Curr Opin Pediatr. 2021;33(2):195–202. doi: 10.1097/MOP.0000000000000999

[68] Hays T., Wapner R.J. Genetic testing for unexplained perinatal disorders // Curr Opin Pediatr. 2021. Vol. 33, N 2. P. 195–202. doi: 10.1097/MOP.0000000000000999

[69] McClure EM, Silver RM, Kim J, et al. Maternal infection and stillbirth: a review. J Matern Fetal Neonatal Med. 2022;35(23):4442–4450. doi: 10.1080/14767058.2020.1852206

[70] McClure E.M., Silver R.M., Kim J., et al. Maternal infection and stillbirth: a review // J Matern Fetal Neonatal Med. 2022. Vol. 35, N 23. P. 4442–4450. doi: 10.1080/14767058.2020.1852206.

[71] Megli CJ, Coyne CB. Infections at the maternal-fetal interface: an overview of pathogenesis and defence. Nat Rev Microbiol. 2022;20(2):67–82. doi: 10.1038/s41579-021-00610-y

[72] Megli C.J., Coyne C.B. Infections at the maternal-fetal interface: an overview of pathogenesis and defence // Nat Rev Microbiol. 2022. Vol. 20, N 2. P. 67–82. doi: 10.1038/s41579-021-00610-y

[73] Aleem S, Bhutta ZA. Infection-related stillbirth: an update on current knowledge and strategies for prevention. Expert Rev Anti Infect Ther. 2021;19(9):1117–1124. doi: 10.1080/14787210.2021.1882849

[74] Aleem S., Bhutta Z.A. Infection-related stillbirth: an update on current knowledge and strategies for prevention // Expert Rev Anti Infect Ther. 2021. Vol. 19, N 9. P. 1117–1124. doi: 10.1080/14787210.2021.1882849

[75] Tantengco OAG, Yanagihara I. Current understanding and treatment of intra-amniotic infection with Ureaplasma spp. J Obstet Gynaecol Res. 2019;45(9):1796–1808. doi: 10.1111/jog.14052

[76] Tantengco O.A.G., Yanagihara I. Current understanding and treatment of intra-amniotic infection with Ureaplasma spp // J Obstet Gynaecol Res. 2019. Vol. 45, N 9. P. 1796–1808. doi: 10.1111/jog.14052

[77] Page JM, Bardsley T, Thorsten V, et al. Stillbirth associated with infection in a diverse U.S. cohort. Obstet Gynecol. 2019;134(6):1187–1196. doi: 10.1097/AOG.0000000000003515

[78] Page J.M., Bardsley T., Thorsten V., et al. Stillbirth associated with infection in a diverse U.S. cohort // Obstet Gynecol. 2019. Vol. 134, N 6. P. 1187–1196. doi: 10.1097/AOG.0000000000003515

[79] Velavan TP, Pallerla SR, Johne R, et al. Hepatitis E: an update on one health and clinical medicine. Liver Int. 2021;41(7):1462–1473. doi: 10.1111/liv.14912

[80] Velavan T.P., Pallerla S.R., Johne R., et al. Hepatitis E: an update on one health and clinical medicine // Liver Int. 2021. Vol. 41, N 7. P. 1462–1473. doi: 10.1111/liv.14912

[81] World Health Organization [Internet]. HIV data and statistics. 2024 [cited 2024 July 22]. Available from: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/strategic-information/hiv-data-and-statistics

[82] World Health Organization [Электронный ресурс]. HIV data and statistics. 2024. Режим доступа: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/strategic-information/hiv-data-and-statistics. Дата обращения: 22.07.2024.

[83] Wedi CO, Kirtley S, Hopewell S, et al. Perinatal outcomes associated with maternal HIV infection: a systematic review and meta-analysis. Lancet HIV. 2016;3(1):e33–e48. doi: 10.1016/S2352-3018(15)00207-6

[84] Wedi C.O., Kirtley S., Hopewell S., et al. Perinatal outcomes associated with maternal HIV infection: a systematic review and meta-analysis // Lancet HIV. 2016. Vol. 3, N 1. P. 33–48. doi: 10.1016/S2352-3018(15)00207-6

[85] Maudhoo A, Khalil A. Viral pulmonary infection in pregnancy — including COVID–19, SARS, influenza A, and varicella. Best Pract Res Clin Obstet Gynaecol. 2022;85(Pt A):17–25. doi: 10.1016/j.bpobgyn.2022.06.006

[86] Maudhoo A., Khalil A. Viral pulmonary infection in pregnancy — including COVID–19, SARS, influenza A, and varicella // Best Pract Res Clin Obstet Gynaecol. 2022. Vol. 85. P. 17–25. doi: 10.1016/j.bpobgyn.2022.06.006

[87] Fell DB, Savitz DA, Kramer MS, et al. Maternal influenza and birth outcomes: systematic review of comparative studies. BJOG. 2017;124(1):48–59. doi: 10.1111/1471-0528.14143

[88] Fell D.B., Savitz D.A., Kramer M.S., et al. Maternal influenza and birth outcomes: systematic review of comparative studies // BJOG. 2017 Vol. 124, N 1. P. 48–59. doi: 10.1111/1471-0528.14143

[89] Liu Y, Liu J. Group B Streptococcus: virulence factors and pathogenic mechanism. Microorganisms. 2022;10(12):2483. doi: 10.3390/microorganisms10122483

[90] Liu Y., Liu J. Group B streptococcus: virulence factors and pathogenic mechanism // Microorganisms. 2022. Vol. 10, N 12. P. 2483. doi: 10.3390/microorganisms10122483

[91] Yuan XY, Liu HZ, Liu JF, et al. Pathogenic mechanism, detection methods and clinical significance of group B Streptococcus. Future Microbiol. 2021;16:671–685. doi: 10.2217/fmb-2020-0189

[92] Yuan X.Y., Liu H.Z., Liu J.F., et al. Pathogenic mechanism, detection methods and clinical significance of group B Streptococcus // Future Microbiol. 2021. Vol. 16. P. 671–685. doi: 10.2217/fmb-2020-0189

[93] Stephens K, Charnock-Jones DS, Smith GCS. Group B streptococcus and the risk of perinatal morbidity and mortality following term labor. Am J Obstet Gynecol. 2023;228(5):1305–1312. doi: 10.1016/j.ajog.2022.07.051

[94] Stephens K., Charnock-Jones D.S., Smith G.C.S. Group B streptococcus and the risk of perinatal morbidity and mortality following term labor // Am J Obstet Gynecol. 2023. Vol. 228, N 5. P. 1305–1312. doi: 10.1016/j.ajog.2022.07.051

[95] Seale AC, Blencowe H, Bianchi-Jassir F, et al. Stillbirth with group B streptococcus disease worldwide: systematic review and meta-analyses. Clin Infect Dis. 2017;65(2):125–132. doi: 10.1093/cid/cix585

[96] Seale A.C., Blencowe H., Bianchi-Jassir F., et al. Stillbirth with group B streptococcus disease worldwide: systematic review and meta-analyses // Clin Infect Dis. 2017 Vol. 65, N 2. P. 125–132. doi: 10.1093/cid/cix585

RIGHTS & PERMISSIONS

Eсо-Vector