Am J Perinatol 2016; 33(14): 1337-1356
DOI: 10.1055/s-0036-1582397
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inflammation in Complicated Pregnancy and Its Outcome

Ram R. Kalagiri
1   Department of Neonatology, Baylor Scott and White Health, Temple, Texas
2   Texas A&M Health Science Center College of Medicine, Temple, Texas
,
Timothy Carder
2   Texas A&M Health Science Center College of Medicine, Temple, Texas
,
Saiara Choudhury
2   Texas A&M Health Science Center College of Medicine, Temple, Texas
,
Niraj Vora
1   Department of Neonatology, Baylor Scott and White Health, Temple, Texas
2   Texas A&M Health Science Center College of Medicine, Temple, Texas
,
Amie R. Ballard
1   Department of Neonatology, Baylor Scott and White Health, Temple, Texas
2   Texas A&M Health Science Center College of Medicine, Temple, Texas
3   Department of Pediatrics, Baylor Scott and White Health, Temple, Texas
,
Vinayak Govande
1   Department of Neonatology, Baylor Scott and White Health, Temple, Texas
2   Texas A&M Health Science Center College of Medicine, Temple, Texas
3   Department of Pediatrics, Baylor Scott and White Health, Temple, Texas
,
Nathan Drever
2   Texas A&M Health Science Center College of Medicine, Temple, Texas
4   Department of Obstetrics and Gynecology, Baylor Scott and White Health, Temple, Texas
,
Madhava R. Beeram
1   Department of Neonatology, Baylor Scott and White Health, Temple, Texas
2   Texas A&M Health Science Center College of Medicine, Temple, Texas
3   Department of Pediatrics, Baylor Scott and White Health, Temple, Texas
,
M. Nasir Uddin
2   Texas A&M Health Science Center College of Medicine, Temple, Texas
3   Department of Pediatrics, Baylor Scott and White Health, Temple, Texas
4   Department of Obstetrics and Gynecology, Baylor Scott and White Health, Temple, Texas
5   Internal Medicine, Baylor Scott and White Health, Temple, Texas
› Author Affiliations
Further Information

Publication History

14 January 2016

26 February 2016

Publication Date:
09 May 2016 (online)

Abstract

Background Normal pregnancy relies on a careful balance between immune tolerance and suppression. It is known that strict regulation of maternal immune function, in addition to components of inflammation, is paramount to successful pregnancy, and any imbalance between proinflammatory and anti-inflammatory cytokines and chemokines can lead to aberrant inflammation, often seen in complicated pregnancies. Inflammation in complicated pregnancies is directly associated with increased mortality and morbidity of the mother and offspring. Aberrant inflammatory reactions in complicated pregnancies often lead to adverse outcomes, such as spontaneous abortion, preterm labor, intrauterine growth restriction, and fetal demise. The role of inflammation in different stages of normal pregnancy is reviewed, compared, and contrasted with aberrant inflammation in complicated pregnancies. The complications addressed are preterm labor, pregnancy loss, infection, preeclampsia, maternal obesity, gestational diabetes mellitus, autoimmune diseases, and inflammatory bowel disease.

Aim This article examines the role of various inflammatory factors contributing to aberrant inflammation in complicated pregnancies. By understanding the aberrant inflammatory process in complicated pregnancies, novel diagnostic tools and therapeutic interventions for modulating it appropriately can be identified.

 
  • References

  • 1 Gotsch F, Romero R, Kusanovic JP. , et al. The fetal inflammatory response syndrome. Clin Obstet Gynecol 2007; 50 (03) 652-683
  • 2 Romero R, Espinoza J, Gonçalves LF, Kusanovic JP, Friel L, Hassan S. The role of inflammation and infection in preterm birth. Semin Reprod Med 2007; 25 (01) 21-39
  • 3 Pařízek A, Koucký M, Dušková M. Progesterone, inflammation and preterm labor. J Steroid Biochem Mol Biol 2014; 139: 159-165
  • 4 Cotechini T, Graham CH. Aberrant maternal inflammation as a cause of pregnancy complications: a potential therapeutic target?. Placenta 2015; 36 (08) 960-966
  • 5 Challis JRG, Matthews SG, Gibb W, Lye SJ. Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev 2000; 21 (05) 514-550
  • 6 Challis JR, Lockwood CJ, Myatt L, Norman JE, Strauss III JF, Petraglia F. Inflammation and pregnancy. Reprod Sci 2009; 16 (02) 206-215
  • 7 Torabi F, Akbari SAA, Amiri S, Soleimani F, Majd HA. Correlation between high-risk pregnancy and developmental delay in children aged 4-60 months. Libyan J Med 2012 7.
  • 8 Kim C. Maternal outcomes and follow-up after gestational diabetes mellitus. Diabet Med 2014; 31 (03) 292-301
  • 9 Stevenson L. Exercise in pregnancy. Part 1: update on pathophysiology. Can Fam Physician 1997; 43: 97-104
  • 10 Eskenazi B, Castorina R. Association of prenatal maternal or postnatal child environmental tobacco smoke exposure and neurodevelopmental and behavioral problems in children. Environ Health Perspect 1999; 107 (12) 991-1000
  • 11 Blanc AK, Winfrey W, Ross J. New findings for maternal mortality age patterns: aggregated results for 38 countries. PLoS ONE 2013; 8 (04) e59864
  • 12 Denison FC, Roberts KA, Barr SM, Norman JE. Obesity, pregnancy, inflammation, and vascular function. Reproduction 2010; 140 (03) 373-385
  • 13 Sykes L, MacIntyre DA, Yap XJ, Ponnampalam S, Teoh TG, Bennett PR. Changes in the Th1:Th2 cytokine bias in pregnancy and the effects of the anti-inflammatory cyclopentenone prostaglandin 15-deoxy-Δ(12,14)-prostaglandin J2. Mediators Inflamm 2012; 2012: 416739
  • 14 Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci 2011; 1221: 80-87
  • 15 Sykes L, MacIntyre DA, Yap XJ, Teoh TG, Bennett PR. The Th1:th2 dichotomy of pregnancy and preterm labour. Mediators Inflamm 2012; 2012: 967629
  • 16 Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010; 63 (06) 601-610
  • 17 Dekel N, Gnainsky Y, Granot I, Mor G. Inflammation and implantation. Am J Reprod Immunol 2010; 63 (01) 17-21
  • 18 Mor G. Inflammation and pregnancy: the role of toll-like receptors in trophoblast-immune interaction. Ann N Y Acad Sci 2008; 1127: 121-128
  • 19 Shynlova O, Lee YH, Srikhajon K, Lye SJ. Physiologic uterine inflammation and labor onset: integration of endocrine and mechanical signals. Reprod Sci 2013; 20 (02) 154-167
  • 20 Hoang M, Potter JA, Gysler SM. , et al. Human fetal membranes generate distinct cytokine profiles in response to bacterial Toll-like receptor and nod-like receptor agonists. Biol Reprod 2014; 90 (02) 39
  • 21 Bates MD, Quenby S, Takakuwa K, Johnson PM, Vince GS. Aberrant cytokine production by peripheral blood mononuclear cells in recurrent pregnancy loss?. Hum Reprod 2002; 17 (09) 2439-2444
  • 22 Adams Waldorf KM, Nelson JL. Autoimmune disease during pregnancy and the microchimerism legacy of pregnancy. Immunol Invest 2008; 37 (05) 631-644
  • 23 McCracken SA, Drury CL, Lee HS, Morris JM. Pregnancy is associated with suppression of the nuclear factor kappaB/IkappaB activation pathway in peripheral blood mononuclear cells. J Reprod Immunol 2003; 58 (01) 27-47
  • 24 Warning JC, McCracken SA, Morris JM. A balancing act: mechanisms by which the fetus avoids rejection by the maternal immune system. Reproduction 2011; 141 (06) 715-724
  • 25 Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol 2010; 63 (06) 425-433
  • 26 Fest S, Aldo PB, Abrahams VM. , et al. Trophoblast-macrophage interactions: a regulatory network for the protection of pregnancy. Am J Reprod Immunol 2007; 57 (01) 55-66
  • 27 Haider S, Knöfler M. Human tumour necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta 2009; 30 (02) 111-123
  • 28 Cotechini T, Komisarenko M, Sperou A, Macdonald-Goodfellow S, Adams MA, Graham CH. Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia. J Exp Med 2014; 211 (01) 165-179
  • 29 Patni S, Wynen LP, Seager AL, Morgan G, White JO, Thornton CA. Expression and activity of Toll-like receptors 1-9 in the human term placenta and changes associated with labor at term. Biol Reprod 2009; 80 (02) 243-248
  • 30 Dabagh-Gorjani F, Anvari F, Zolghadri J, Kamali-Sarvestani E, Gharesi-Fard B. Differences in the expression of TLRs and inflammatory cytokines in pre-eclamptic compared with healthy pregnant women. Iran J Immunol 2014; 11 (04) 233-245
  • 31 Zhou L, Li R, Wang R, Huang HX, Zhong K. Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates. Fertil Steril 2008; 89 (05) 1166-1176
  • 32 Zhang S, Kong S, Lu J. , et al. Deciphering the molecular basis of uterine receptivity. Mol Reprod Dev 2013; 80 (01) 8-21
  • 33 Hanna J, Goldman-Wohl D, Hamani Y. , et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med 2006; 12 (09) 1065-1074
  • 34 Nagamatsu T, Schust DJ. The contribution of macrophages to normal and pathological pregnancies. Am J Reprod Immunol 2010; 63 (06) 460-471
  • 35 Shynlova O, Tsui P, Dorogin A, Lye SJ. Monocyte chemoattractant protein-1 (CCL-2) integrates mechanical and endocrine signals that mediate term and preterm labor. J Immunol 2008; 181 (02) 1470-1479
  • 36 Plaks V, Birnberg T, Berkutzki T. , et al. Uterine DCs are crucial for decidua formation during embryo implantation in mice. J Clin Invest 2008; 118 (12) 3954-3965
  • 37 Birnberg T, Plaks V, Berkutzki T. , et al. Dendritic cells are crucial for decidual development during embryo implantation. Am J Reprod Immunol 2007; 57: 342
  • 38 Uddin MN, Horvat D, Jones RO. , et al. Suppression of aldosterone and progesterone in preeclampsia. J Matern Fetal Neonatal Med 2015; 28 (11) 1-6
  • 39 Chatterjee P, Chiasson VL, Bounds KR, Mitchell BM. Regulation of the anti-inflammatory cytokines interleukin-4 and interleukin-10 during pregnancy. Front Immunol 2014; 5: 253
  • 40 Romero R, Durum SK, Dinarello CA. , et al. Interleukin-1: a signal for the initiation of labor in chorioamnionitis. Paper presented at: 33rd Annual Meeting for the Society for Gynecologic Investigation; 1986; Toronto, Canada
  • 41 Romero R, Mazor M, Tartakovsky B. Systemic administration of interleukin-1 induces preterm parturition in mice. Am J Obstet Gynecol 1991; 165 (4, Pt 1) 969-971
  • 42 Romero R, Tartakovsky B. The natural interleukin-1 receptor antagonist prevents interleukin-1-induced preterm delivery in mice. Am J Obstet Gynecol 1992; 167 (4, Pt 1) 1041-1045
  • 43 Ng PY, Ireland DJ, Keelan JA. Drugs to block cytokine signaling for the prevention and treatment of inflammation-induced preterm birth. Front Immunol 2015; 6: 166
  • 44 Kiprono LV, Wallace K, Moseley J, Martin J, LaMarca B. Progesterone blunts vascular endothelial cell secretion of endothelin-1 in response to placental ischemia. Am J Obstet Gynecol 2013; 209: 44.e1-44.e6
  • 45 Lamarca B. The role of immune activation in contributing to vascular dysfunction and the pathophysiology of hypertension during preeclampsia. Minerva Ginecol 2010; 62 (02) 105-120
  • 46 Norwitz ER, Caughey AB. Progesterone supplementation and the prevention of preterm birth. Rev Obstet Gynecol 2011; 4 (02) 60-72
  • 47 Keelan JA. Pharmacological inhibition of inflammatory pathways for the prevention of preterm birth. J Reprod Immunol 2011; 88 (02) 176-184
  • 48 De Silva D, Mitchell MD, Keelan JA. Inhibition of choriodecidual cytokine production and inflammatory gene expression by selective I-kappaB kinase (IKK) inhibitors. Br J Pharmacol 2010; 160 (07) 1808-1822
  • 49 Bain J, Plater L, Elliott M. , et al. The selectivity of protein kinase inhibitors: a further update. Biochem J 2007; 408 (03) 297-315
  • 50 Galinsky R, Polglase GR, Hooper SB, Black MJ, Moss TJ. The consequences of chorioamnionitis: preterm birth and effects on development. J Pregnancy 2013; 2013: 412831
  • 51 Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol 1998; 179 (01) 194-202
  • 52 Cohen J, Ghezzi F, Romero R. , et al. GRO alpha in the fetomaternal and amniotic fluid compartments during pregnancy and parturition. Am J Reprod Immunol 1996; 35 (01) 23-29
  • 53 Yüce O, Biçer OS, Kavuncuoğlu S, Ozelgün B, Ongüt C. Prematurity, infection, mortality, morbidity and interleukins: the reason or the result of preterm labor?. Minerva Pediatr 2014; 66 (06) 563-570
  • 54 Urakubo A, Jarskog LF, Lieberman JA, Gilmore JH. Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain. Schizophr Res 2001; 47 (01) 27-36
  • 55 Romero R, Miranda J, Chaiworapongsa T. , et al. Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol 2014; 72 (05) 458-474
  • 56 Bryant-Greenwood GD, Kern A, Yamamoto SY, Sadowsky DW, Novy MJ. Relaxin and the human fetal membranes. Reprod Sci 2007; 14 (8, Suppl): 42-45
  • 57 Combs CA, Gravett M, Garite TJ. , et al; ProteoGenix/Obstetrix Collaborative Research Network. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol 2014; 210 (02) 125.e1-125.e15
  • 58 Zhou CC, Zhang Y, Irani RA. , et al. Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. Nat Med 2008; 14 (08) 855-862
  • 59 Lamarca B, Brewer J, Wallace K. IL-6-induced pathophysiology during pre-eclampsia: potential therapeutic role for magnesium sulfate?. Int J Interferon Cytokine Mediat Res 2011; 2011 (03) 59-64
  • 60 Xia Y, Kellems RE. Angiotensin receptor agonistic autoantibodies and hypertension: preeclampsia and beyond. Circ Res 2013; 113 (01) 78-87
  • 61 Redman CW, Sargent IL. Pre-eclampsia, the placenta and the maternal systemic inflammatory response—a review. Placenta 2003; 24 (Suppl A): S21-S27
  • 62 Lamarca B, Speed J, Ray LF. , et al. Hypertension in response to IL-6 during pregnancy: role of AT1-receptor activation. Int J Interferon Cytokine Mediat Res 2011; 2011 (03) 65-70
  • 63 Brewer J, Liu R, Lu Y. , et al. Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy. Hypertension 2013; 62 (05) 886-892
  • 64 Xia Y, Kellems RE. Is preeclampsia an autoimmune disease?. Clin Immunol 2009; 133 (01) 1-12
  • 65 Zhou CC, Ahmad S, Mi T. , et al. Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling. Hypertension 2008; 51 (04) 1010-1019
  • 66 Bergmann A, Ahmad S, Cudmore M. , et al. Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model. J Cell Mol Med 2010; 14 (6B) 1857-1867
  • 67 Dechend R, Homuth V, Wallukat G. , et al. AT(1) receptor agonistic antibodies from preeclamptic patients cause vascular cells to express tissue factor. Circulation 2000; 101 (20) 2382-2387
  • 68 Lin S, Leonard D, Co MA. , et al. Pre-eclampsia has an adverse impact on maternal and fetal health. Transl Res 2015; 165 (04) 449-463
  • 69 Warrington JP, George EM, Palei AC, Spradley FT, Granger JP. Recent advances in the understanding of the pathophysiology of preeclampsia. Hypertension 2013; 62 (04) 666-673
  • 70 Siddiqui AH, Irani RA, Blackwell SC, Ramin SM, Kellems RE, Xia Y. Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: correlation with disease severity. Hypertension 2010; 55 (02) 386-393
  • 71 Jensen F, Wallukat G, Herse F. , et al. CD19+CD5+ cells as indicators of preeclampsia. Hypertension 2012; 59 (04) 861-868
  • 72 Skinner SL, Lumbers ER, Symonds EM. Analysis of changes in the renin-angiotensin system during pregnancy. Clin Sci 1972; 42 (04) 479-488
  • 73 Brown MA, Zammit VC, Mitar DA, Whitworth JA. Renin-aldosterone relationships in pregnancy-induced hypertension. Am J Hypertens 1992; 5 (6, Pt 1) 366-371
  • 74 Symonds EM, Broughton Pipkin F, Craven DJ. Changes in the renin-angiotensin system in primigravidae with hypertensive disease of pregnancy. Br J Obstet Gynaecol 1975; 82 (08) 643-650
  • 75 Abdul-Karim R, Assalin S. Pressor response to angiotonin in pregnant and nonpregnant women. Am J Obstet Gynecol 1961; 82: 246-251
  • 76 Cooper AC, Robinson G, Vinson GP, Cheung WT, Broughton Pipkin F. The localization and expression of the renin-angiotensin system in the human placenta throughout pregnancy. Placenta 1999; 20 (5–6) 467-474
  • 77 Nielsen AH, Schauser KH, Poulsen K. Current topic: the uteroplacental renin-angiotensin system. Placenta 2000; 21 (5–6) 468-477
  • 78 Morgan T, Craven C, Ward K. Human spiral artery renin-angiotensin system. Hypertension 1998; 32 (04) 683-687
  • 79 Li C, Ansari R, Yu Z, Shah D. Definitive molecular evidence of renin-angiotensin system in human uterine decidual cells. Hypertension 2000; 36 (02) 159-164
  • 80 Uddin MN, Agunanne E, Horvat D, Puschett JB. Alterations in the renin-angiotensin system in a rat model of human preeclampsia. Am J Nephrol 2010; 31 (02) 171-177
  • 81 Uddin MN, Allen SR, Jones RO, Zawieja DC, Kuehl TJ. Pathogenesis of pre-eclampsia: marinobufagenin and angiogenic imbalance as biomarkers of the syndrome. Transl Res 2012; 160 (02) 99-113
  • 82 Brar HS, Kjos SL, Dougherty W, Do YS, Tam HB, Hsueh WA. Increased fetoplacental active renin production in pregnancy-induced hypertension. Am J Obstet Gynecol 1987; 157 (02) 363-367
  • 83 Leung PS, Tsai SJ, Wallukat G, Leung TN, Lau TK. The upregulation of angiotensin II receptor AT(1) in human preeclamptic placenta. Mol Cell Endocrinol 2001; 184 (1–2) 95-102
  • 84 Ito M, Itakura A, Ohno Y. , et al. Possible activation of the renin-angiotensin system in the feto-placental unit in preeclampsia. J Clin Endocrinol Metab 2002; 87 (04) 1871-1878
  • 85 Cawyer CR, Horvat D, Leonard D. , et al. Hyperglycemia impairs cytotrophoblast function via stress signaling. Am J Obstet Gynecol 2014; 211 (05) 541.e1-541.e8
  • 86 Bagrov AY, Shapiro JI, Fedorova OV. Endogenous cardiotonic steroids: physiology, pharmacology, and novel therapeutic targets. Pharmacol Rev 2009; 61 (01) 9-38
  • 87 Bagrov AY, Fedorova OV. Effects of two putative endogenous digitalis-like factors, marinobufagenin and ouabain, on the Na+, K+-pump in human mesenteric arteries. J Hypertens 1998; 16 (12, Pt 2) 1953-1958
  • 88 Uddin MN, Horvat D, Glaser SS, Mitchell BM, Puschett JB. Examination of the cellular mechanisms by which marinobufagenin inhibits cytotrophoblast function. J Biol Chem 2008; 283 (26) 17946-17953
  • 89 LaMarca HL, Morris CA, Pettit GR, Nagowa T, Puschett JB. Marinobufagenin impairs first trimester cytotrophoblast differentiation. Placenta 2006; 27 (9–10) 984-988
  • 90 Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med 2001; 345 (19) 1400-1408
  • 91 Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol 1989; 161 (05) 1200-1204
  • 92 Uddin MN, Horvat D, Glaser SS. , et al. Marinobufagenin inhibits proliferation and migration of cytotrophoblast and CHO cells. Placenta 2008; 29 (03) 266-273
  • 93 Agunanne EE, Uddin MN, Horvat D, Puschett JB. Contribution of angiogenic factors in a rat model of pre-eclampsia. Am J Nephrol 2010; 32 (04) 332-339
  • 94 Uddin MN, McLean LB, Hunter FA. , et al. Vascular leak in a rat model of preeclampsia. Am J Nephrol 2009; 30 (01) 26-33
  • 95 Uddin MN, Horvat D, Childs EW, Puschett JB. Marinobufagenin causes endothelial cell monolayer hyperpermeability by altering apoptotic signaling. Am J Physiol Regul Integr Comp Physiol 2009; 296 (06) R1726-R1734
  • 96 Ehrig JC, Horvat D, Allen SR, Jones RO, Kuehl TJ, Uddin MN. Cardiotonic steroids induce anti-angiogenic and anti-proliferative profiles in first trimester extravillous cytotrophoblast cells. Placenta 2014; 35 (11) 932-936
  • 97 Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010; 376 (9741) 631-644
  • 98 Hunter A, Aitkenhead M, Caldwell C, McCracken G, Wilson D, McClure N. Serum levels of vascular endothelial growth factor in preeclamptic and normotensive pregnancy. Hypertension 2000; 36 (06) 965-969
  • 99 Staff AC, Dechend R, Redman CW. Review: preeclampsia, acute atherosis of the spiral arteries and future cardiovascular disease: two new hypotheses. Placenta 2013; 34 (Suppl): S73-S78
  • 100 Backes CH, Markham K, Moorehead P, Cordero L, Nankervis CA, Giannone PJ. Maternal preeclampsia and neonatal outcomes. J Pregnancy 2011; 2011: 214365
  • 101 Segovia SA, Vickers MH, Gray C, Reynolds CM. Maternal obesity, inflammation, and developmental programming. Biomed Res Int 2014; 2014: 418975
  • 102 Challier JC, Basu S, Bintein T. , et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 2008; 29 (03) 274-281
  • 103 Wolf M, Sauk J, Shah A. , et al. Inflammation and glucose intolerance: a prospective study of gestational diabetes mellitus. Diabetes Care 2004; 27 (01) 21-27
  • 104 Ramsay JE, Ferrell WR, Crawford L, Wallace AM, Greer IA, Sattar N. Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. J Clin Endocrinol Metab 2002; 87 (09) 4231-4237
  • 105 Roberts KA, Riley SC, Reynolds RM. , et al. Placental structure and inflammation in pregnancies associated with obesity. Placenta 2011; 32 (03) 247-254
  • 106 Uddin MN, Beeram MR, Kuehl TJ. Diabetes mellitus and preeclampsia. Med J Obstet Gynecol 2013; 1 (03) 1016
  • 107 Suwaki N, Masuyama H, Masumoto A, Takamoto N, Hiramatsu Y. Expression and potential role of peroxisome proliferator-activated receptor gamma in the placenta of diabetic pregnancy. Placenta 2007; 28 (04) 315-323
  • 108 Vrachnis N, Belitsos P, Sifakis S. , et al. Role of adipokines and other inflammatory mediators in gestational diabetes mellitus and previous gestational diabetes mellitus. Int J Endocrinol 2012; 2012: 549748
  • 109 Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352 (24) 2477-2486
  • 110 Xu J, Zhao YH, Chen YP. , et al. Maternal circulating concentrations of tumor necrosis factor-alpha, leptin, and adiponectin in gestational diabetes mellitus: a systematic review and meta-analysis. ScientificWorldJournal 2014; 2014: 926932
  • 111 Miehle K, Stepan H, Fasshauer M. Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol (Oxf) 2012; 76 (01) 2-11
  • 112 Mrizak I, Arfa A, Fekih M. , et al. Inflammation and impaired endothelium-dependant vasodilatation in non obese women with gestational diabetes mellitus: preliminary results. Lipids Health Dis 2013; 12: 93
  • 113 Zen M, Ghirardello A, Iaccarino L. , et al. Hormones, immune response, and pregnancy in healthy women and SLE patients. Swiss Med Wkly 2010; 140 (13–14) 187-201
  • 114 de Jesus GR, Mendoza-Pinto C, de Jesus NR. , et al. Understanding and managing pregnancy in patients with lupus. Autoimmune Dis 2015; 2015: 943490
  • 115 Jara LJ, Medina G, Cruz-Dominguez P, Navarro C, Vera-Lastra O, Saavedra MA. Risk factors of systemic lupus erythematosus flares during pregnancy. Immunol Res 2014; 60 (2–3) 184-192
  • 116 Chan GW, Mandel SJ. Therapy insight: management of Graves' disease during pregnancy. Nat Clin Pract Endocrinol Metab 2007; 3 (06) 470-478
  • 117 Kung AW, Lau KS, Kohn LD. Epitope mapping of tsh receptor-blocking antibodies in Graves' disease that appear during pregnancy. J Clin Endocrinol Metab 2001; 86 (08) 3647-3653
  • 118 Jones BM, Kwok JSY, Kung AWC. Changes in cytokine production during pregnancy in patients with Graves' disease. Thyroid 2000; 10 (08) 701-707
  • 119 Saha S, Wald A. Safety and efficacy of immunomodulators and biologics during pregnancy and lactation for the treatment of inflammatory bowel disease. Expert Opin Drug Saf 2012; 11 (06) 947-957
  • 120 Korelitz BI. Inflammatory bowel disease and pregnancy. Gastroenterol Clin North Am 1998; 27 (01) 213-224
  • 121 Beaulieu DB, Kane S. Inflammatory bowel disease in pregnancy. Gastroenterol Clin North Am 2011; 40 (02) 399-413
  • 122 Alstead EM. Inflammatory bowel disease in pregnancy. Postgrad Med J 2002; 78 (915) 23-26
  • 123 Cornish J, Tan E, Teare J. , et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut 2007; 56 (06) 830-837
  • 124 Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res 2009; 29 (06) 313-326
  • 125 Chatterjee P, Chiasson VL, Kopriva SE. , et al. Interleukin 10 deficiency exacerbates toll-like receptor 3-induced preeclampsia-like symptoms in mice. Hypertension 2011; 58 (03) 489-496
  • 126 Costantine MM, Cleary K. Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric--Fetal Pharmacology Research Units Network. Pravastatin for the prevention of preeclampsia in high-risk pregnant women. Obstet Gynecol 2013; 121 (2, Pt 1) 349-353
  • 127 Vu H, Ianosi-Irimie M, Danchuk S. , et al. Resibufogenin corrects hypertension in a rat model of human preeclampsia. Exp Biol Med (Maywood) 2006; 231 (02) 215-220
  • 128 Horvat D, Severson J, Uddin MN, Mitchell B, Puschett JB. Resibufogenin prevents the manifestations of preeclampsia in an animal model of the syndrome. Hypertens Pregnancy 2010; 29 (01) 1-9
  • 129 Puschett JB, Agunanne E, Uddin MN. Marinobufagenin, resibufogenin and preeclampsia. Biochim Biophys Acta 2010; 1802 (12) 1246-1253
  • 130 Fedorova OV, Simbirtsev AS, Kolodkin NI. , et al. Monoclonal antibody to an endogenous bufadienolide, marinobufagenin, reverses preeclampsia-induced Na/K-ATPase inhibition and lowers blood pressure in NaCl-sensitive hypertension. J Hypertens 2008; 26 (12) 2414-2425