PMID- 28054230
OWN - NLM
STAT- MEDLINE
DCOM- 20180329
LR  - 20220409
IS  - 1559-0267 (Electronic)
IS  - 1080-0549 (Linking)
VI  - 53
IP  - 1
DP  - 2017 Aug
TI  - Tumor Necrosis Factor-Alpha and Pregnancy: Focus on Biologics. An Updated and 
      Comprehensive Review.
PG  - 40-53
LID - 10.1007/s12016-016-8596-x [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a central regulator of inflammation, and TNF-alpha 
      antagonists may be effective in treating inflammatory disorders in which TNF-alpha 
      plays a major pathogenic role. TNF-alpha has also been associated with inflammatory 
      mechanisms related to implantation, placentation, and pregnancy outcome. TNF-alpha is 
      secreted by immune cells and works by binding to TNFR1 and TNFR2 cell receptors. 
      TNF-alpha is also related to JAK/STAT pathways, which opens up hypothetical new 
      targets for modifying. The accurate balance between Th1 cytokines, mainly TNF-alpha, 
      Th17, and Th2, particularly IL-10 is essential to achieve good obstetric 
      outcomes. TNF-alpha targeted therapy could be rational in treating women with 
      obstetric complication related to overproduction of TNF-alpha, such as recurrent 
      pregnancy loss, early and severe pre-eclampsia, and recurrent implantation 
      failure syndrome, all "idiopathic" or related to aPL positivity. Along the same 
      lines, Th1 cytokines, mainly TNF- alpha, play a leading pathogenic role in rheumatic 
      and systemic autoimmune diseases occurring in women and, to a lesser extent, in 
      men of reproductive age. These disorders have to be clinically silent before 
      pregnancy can be recommended, which is usually only possible to achieve after 
      intensive anti-inflammatory and immunosuppressive treatment, TNF-alpha blockers 
      included. Physicians should be aware of the theoretic potential but low 
      embryo-fetal toxicity risk of these drugs during pregnancy. From an updated 
      review in May 2016, we can conclude that TNF-alpha blockers are useful in certain 
      "refractory" cases of inflammatory disorders related to poor obstetric outcomes 
      and infertility. Furthermore, TNF-alpha blockers can be safely used during the 
      implantation period and pregnancy. Breastfeeding is also permitted with all TNF-alpha 
      inhibitors. Since data on the actual mechanism of action of JAK-STAT in 
      inflammatory obstetric disorders including embryo implantation are scarce, for 
      the time being, therapeutic interventions in this setting should be discouraged. 
      Finally, adverse effects on sperm quality, or causing embryo-fetal anomalies, in 
      men treated with TNF inhibitors have not been described.
FAU - Alijotas-Reig, Jaume
AU  - Alijotas-Reig J
AD  - Systemic Autoimmune Diseases Unit, Department of Internal Medicine-1, Vall 
      d'Hebron University Hospital, Passeig Vall d'Hebron 119-129, 08035, Barcelona, 
      Spain. jalijotas@vhebron.net.
AD  - Department of Medicine, Faculty of Medicine, Universitat Autonoma de Barcelona, 
      Barcelona, Spain. jalijotas@vhebron.net.
FAU - Esteve-Valverde, Enrique
AU  - Esteve-Valverde E
AD  - Department of Internal Medicine, Althaia Network Health, Manresa, Barcelona, 
      Spain.
FAU - Ferrer-Oliveras, Raquel
AU  - Ferrer-Oliveras R
AD  - Obstetric High Risk Unit, Obstetric Department, Vall d'Hebron University 
      Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain.
FAU - Llurba, Elisa
AU  - Llurba E
AD  - Obstetric High Risk Unit, Obstetric Department, Vall d'Hebron University 
      Hospital, Barcelona, Spain.
AD  - Pediatric, Obstetric and Gynecology Department, Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
FAU - Gris, Josep Maria
AU  - Gris JM
AD  - Reproductive Medicine Unit, Obstetric Department, Vall d'Hebron University 
      Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Clin Rev Allergy Immunol
JT  - Clinical reviews in allergy & immunology
JID - 9504368
RN  - 0 (Antimalarials)
RN  - 0 (Biological Products)
RN  - 0 (Cytokines)
RN  - 0 (STAT Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.2 (Janus Kinases)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - Abortion, Habitual/immunology/metabolism
MH  - Antimalarials/pharmacology
MH  - Biological Products
MH  - Cytokines/metabolism
MH  - Embryo Implantation
MH  - Female
MH  - Fertilization in Vitro
MH  - Humans
MH  - Janus Kinases/metabolism
MH  - Male
MH  - Paternal Exposure
MH  - Pentoxifylline/pharmacology
MH  - Pre-Eclampsia/immunology/metabolism
MH  - Pregnancy
MH  - STAT Transcription Factors/metabolism
MH  - T-Lymphocyte Subsets/immunology/metabolism
MH  - Th1 Cells/immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/genetics/*metabolism
OTO - NOTNLM
OT  - Antiphospholipid syndrome
OT  - Implantation failure
OT  - JAK-STAT
OT  - Pre-eclampsia
OT  - Recurrent abortion
OT  - TNF-alpha blockers
OT  - Th1-cytokines
EDAT- 2017/01/06 06:00
MHDA- 2018/03/30 06:00
CRDT- 2017/01/06 06:00
PHST- 2017/01/06 06:00 [pubmed]
PHST- 2018/03/30 06:00 [medline]
PHST- 2017/01/06 06:00 [entrez]
AID - 10.1007/s12016-016-8596-x [pii]
AID - 10.1007/s12016-016-8596-x [doi]
PST - ppublish
SO  - Clin Rev Allergy Immunol. 2017 Aug;53(1):40-53. doi: 10.1007/s12016-016-8596-x.