Microcirculation disorders in pregnant women with arterial hypertension and risks of infectious complications in newborns

Neonatal sepsis is the main cause of neonatal mortality. Low birth weight, premature birth, arterial hypertension of pregnant women increase the risk of neonatal sepsis and an unfavorable outcome. Premature infants and low birth weight infants often have neutropenia, which increases the risk of infection and worsens the course of bacterial infection. Neutropenia is more common in newborns from mothers with arterial hypertension of pregnant women than in children from normotensive pregnancy. Arterial hypertension in pregnant women leads to impaired remodeling of spiral arteries and changes in microvessels in the placental bed. The inability to transform the uteroplacental spiral arteries is believed to underlie pregnancy disorders, including preeclampsia and fetal growth retardation. Modern diagnostic methods such as capillaroscopy allow noninvasively assessing the state of the microcirculatory system. The risk of infection of the fetus and newborn is influenced by the microbiome of a pregnant woman, changes in which can lead to a decrease in adaptive immunity, vascular dysfunction and eclampsia. The results of the conducted studies indicate that arterial hypertension in pregnant women is associated with the risk of premature birth and low birth weight, placental insufficiency, neutropenia of newborns, changes in the microbiome, and microcirculatory disorders. Each of these factors increases the risk of neonatal sepsis and affects the outcome of the disease. Blood pressure monitoring can be considered as a preventive measure not only for eclampsia and other complications of pregnancy and childbirth, but also for the prevention of neonatal sepsis.

1. Chan GJ, Lee AC, Baqui AH, Tan J, Black RE. Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis. PLoS Med. 2013 Aug;10(8): e1001502. DOI: 10.1371/journal.pmed.1001502.

2. Congenital pneumonia. Clinical guidelines of the Russian Federation 2025. (In Russ.). https://diseases.medelement.com/disease

3. Sepsis of newborns. Clinical guidelines of the Russian Federation 2025. (In Russ.). https://diseases. medelement.com/disease

4. Cortese F, Scicchitano P, Gesualdo M, Filaninno A, De Giorgi E, Schettini F, Laforgia N, Ciccone MM. Early and Late Infections in Newborns: Where Do We Stand? A Review. Pediatr Neonatol. 2016 Aug; 57 (4): 265–73. DOI: 10.1016/j.pedneo.2015.09.007

5. Al-Adnani M, Sebire NJ. The role of perinatal pathological examination in subclinical infection in obstetrics. Best Pract Res Clin Obstet Gynaecol. 2007 Jun; 21 (3): 505–21. DOI: 10.1016/j.bpobgyn.2007.02.001

6. Manzoni P, Rizzollo S, Mostert M, Farina D. Preeclampsia, neutropenia, and risk of fungal sepsis in preterm very low birth weight infants. J Pediatr. 2011 Jan; 158 (1): 173–4; author reply 174. DOI: 10.1016/j.jpeds.2010.09.057

7. Mahtab S, Madhi SA, Baillie VL, Els T, Thwala BN, Onyango D. et al. CHAMPS Consortium. Causes of death identified in neonates enrolled through Child Health and Mortality Prevention Surveil- lance (CHAMPS), December 2016 – December 2021. PLOS Glob Public Health. 2023 Mar 20; 3 (3): e0001612. DOI: 10.1371/journal.pgph.0001612

8. Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol. 1998 Nov; 179 (5): 1359–75. DOI: 10.1016/s0002-9378(98)70160-7

9. Park YH, Lee GM, Yoon JM, Cheon EJ, Ko KO, Lee YH, Lim JW. Effect of early postnatal neutropenia in very low birth weight infants born to mothers with pregnancy-induced hypertension. Korean J Pediatr. 2012 Dec; 55 (12): 462–9. DOI: 10.3345/kjp.2012.55.12.462

10. Cadnapaphornchai M, Faix RG. Increased nosocomial infection in neutropenic low birth weight (2000 grams or less) infants of hypertensive mothers. J Pediatr. 1992 Dec; 121 (6): 956–61. DOI: 10.1016/s0022-3476 (05) 80351-8

11. Arce-López KL, Iglesias-Leboreiro J, Bernárdez-Zapata I, Rendón-Macías ME, Miranda Madrazo MR. Hematological disorders in preterm newborns born to mothers with pregnancy-induced hypertension. Bol Med Hosp Infant Mex. 2022; 79 (6): 363–368. English. DOI: 10.24875/BMHIM.22000069

12. Fraser SH, Tudehope DI. Neonatal neutropenia and thrombocytopenia following maternal hypertension. J Paediatr Child Health. 1996 Feb; 32 (1): 31–4. DOI: 10.1111/j.1440-1754.1996.tb01537.x

13. Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med. 1989 Aug 31; 321 (9): 557–62. DOI: 10.1056/NEJM198908313210901

14. Doron MW, Makhlouf RA, Katz VL, Lawson EE, Stiles AD. Increased incidence of sepsis at birth in neutropenic infants of mothers with preeclampsia. J Pediatr. 1994 Sep; 125 (3): 452–8. DOI: 10.1016/s0022–3476(05)83294-9

15. Sharma G, Nesin M, Feuerstein M, Bussel JB. Maternal and neonatal characteristics associated with neonatal neutropenia in hypertensive pregnancies. Am J Perinatol. 2009 Oct; 26 (9): 683–9. DOI: 10.1055/s-0029-1223270

16. Funke A, Berner R, Traichel B, Schmeisser D, Leititis JU, Niemeyer CM. Frequency, natural course, and outcome of neonatal neutropenia. Pediatrics. 2000 Jul; 106 (1 Pt 1): 45–51. DOI: 10.1542/peds.106

17. Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB. Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet J Rare Dis. 2011 May 19; 6: 26. DOI: 10.1186/1750-1172-6-26

18. Maheshwari A. Neutropenia in the newborn. Curr Opin Hematol. 2014 Jan; 21 (1): 43–9. DOI: 10.1097/MOH.0000000000000010

19. Okoye HC, Eweputanna LI, Korubo KI, Ejele OA. Effects of maternal hypertension on the neonatal haemogram in southern Nigeria: A case-control study. Malawi Med J. 2016 Dec; 28 (4): 174–178. DOI: 10.4314/mmj.v28i4.5

20. Carr R, Huizinga TW. Low soluble FcRIII receptor demonstrates reduced neutrophil reserves in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 2000 Sep; 83 (2): F160. DOI: 10.1136/fn.83.2.f160

21. Källman J, Schollin J, Schalèn C, Erlandsson A, Kihlström E. Impaired phagocytosis and opsonisation towards group B streptococci in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 1998 Jan; 78 (1): F46–50. DOI: 10.1136/fn.78.1.f46

22. Jiao J, Dragomir AC, Kocabayoglu P, Rahman AH, Chow A, Hashimoto D и соавт. Central role of conventional dendritic cells in regulation of bone marrow release and survival of neutrophils. J Immunol. 2014 Apr 1; 192 (7): 3374–82. DOI: 10.4049/jimmunol.1300237

23. Janssens Y, Nielandt J, Bronselaer A, Debunne N, Verbeke F, Wynendaele E, Van Immerseel F, Vandewynckel YP, De Tré G, De Spiegeleer B. Disbiome database: linking the microbiome to disease. BMC Microbiol. 2018 Jun 4;18(1):50. DOI: 10.1186/s12866-018-1197-5.

24. Dimitriadis E, Rolnik DL, Zhou W, Estrada-Gutierrez G, Koga K, Francisco RPV и соавт. Pre-eclampsia. Nat Rev Dis Primers. 2023 Feb 16; 9 (1): 8. DOI: 10.1038/s41572-023-00417-6. Erratum in: Nat Rev Dis Primers. 2023 Jul 3; 9(1): 35. DOI: 10.1038/s41572-023-00451-4

25. Jordan MM, Amabebe E, Khanipov K, Taylor BD. Scoping Review of Microbiota Dysbiosis and Risk of Preeclampsia. Am J Reprod Immunol. 2024 Oct; 92 (4): e70003. DOI: 10.1111/aji.70003

26. Ponder KL, Bárcena A, Bos FL, Gormley M, Zhou Y, Ona K, Kapidzic M, Zovein AC, Fisher SJ. Preeclampsia and Inflammatory Preterm Labor Alter the Human Placental Hematopoietic Niche. Reprod Sci. 2016 Sep; 23 (9): 1179–92. DOI: 10.1177/1933719116632926

27. Espinoza J, Romero R, Mee Kim Y, Kusanovic JP, Hassan S, Erez O, Gotsch F, Than NG, Papp Z, Jai Kim C. Normal and abnormal transformation of the spiral arteries during pregnancy. J Perinat Med. 2006; 34 (6): 447–58. DOI: 10.1515/JPM.2006.089

28. Brosens I, Robertson WB, Dixon HG. The physiological response of the vessels of the placental bed to normal pregnancy. J Pathol Bacteriol. 1967 Apr; 93 (2): 569–79. DOI: 10.1002/path.1700930218

29. Freise L, Behncke RY, Allerkamp HH, Sandermann TH, Chu NH, Funk EM и соавт.Three-Dimensional Histological Characterization of the Placental Vasculature Using Light Sheet Microscopy. Biomolecules. 2023 Jun 17; 13 (6): 1009. DOI: 10.3390/biom13061009

30. Brosens I, Pijnenborg R, Vercruysse L, Romero R. The «Great Obstetrical Syndromes» are associated with disorders of deep placentation. Am J Obstet Gynecol. 2011 Mar; 204 (3): 193–201. DOI: 10.1016/j.ajog.2010.08.009

31. Brosens I, Puttemans P, Benagiano G. Placental bed research: I. The placental bed: from spiral arteries remodeling to the great obstetrical syndromes. Am J Obstet Gynecol. 2019 Nov; 221 (5): 437–456. DOI: 10.1016/j.ajog.2019.05.044

32. Kim YM, Bujold E, Chaiworapongsa T, Gomez R, Yoon BH, Thaler HT, Rotmensch S, Romero R. Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 2003 Oct; 189 (4): 1063–9. DOI: 10.1067/s0002–9378(03)00838-x

33. Lyall F, Robson SC, Bulmer JN. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome. Hypertension. 2013 Dec; 62 (6): 1046–54. DOI: 10.1161/HYPERTENSIONAHA.113.01892

34. Peng M, Yu L, Ding YL, Zhou CJ. [Trophoblast cells invaing the placenta bed and change of spiral arteries and microvessels in pre-eclampsia]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2008 Feb; 33 (2): 121–9. Chinese. PMID: 18326906.

35. Phillipos J, Luong TV, Chang D, Varadarajan S, Howat P, Hodgson L, Colville D, Savige J. Retinal small vessel narrowing in women with gestational diabetes, pregnancy-associated hypertension, or small-for-gestational age babies. Front Med (Lausanne). 2023 Oct 16; 10: 1265555. DOI: 10.3389/fmed.2023.1265555

36. Li LJ, Aris I, Su LL, Tint MT, Cheung CY, Ikram MK. et al. Associations of maternal retinal vasculature with subsequent fetal growth and birth size. PLoS One. 2015 Apr 24; 10 (4): e0118250. DOI: 10.1371/journal.pone.0118250

37. Feihl F., Liaudet L., Waeber B. The macrocirculation and microcirculation of hypertension. Current Hypertension Reports. 2009; 11 (3): 182–189.