Tuesday, 11 August 2020

Intra uterine Foeatl deaths and investigations thereof

 

What tests that has to be done in a case of RPL / unexplained & unpredicted IUFD near term??. Tests which are worth doing are: as follows:

Part I: common tests for  Extrauterine disorders causing IUFD/ RPL?  –To enquire detailed of medical diseases , occupation, drug/ substance abuse.,  family history of such malady(?genetic cause of Rec IUFD) , any  consanguinity, any operation, Work place toxicity,

Uncommon Lab tests before the dead baby is disposed: Before I describe the schedule Lab tets I like to draw attention of all members that any unexplained IUFD warrants   peripheral blood karyotyping(blood  drawn from foetal heart): of such a method is  approved by couple and such  facilities exists at your town and city -,Source of sample will be more representative  from  foetal skin tissue instead of blood , Microarray /cGH can be considered because  many a mutation diosrder can’t be picked up traditional karyotype. In about 5% of all RPL are due to balanced Translocation particularly 22q11.2 ( long arm of Chr 22 locus), So there is a relevance of  Cytogenetic analysis of the products of conception, Foetal/POC chromosome  

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Commonly performed Lab tests:      Complete haemogram, Thalassaemia screening, HBA1c, OGTT, Viral Serology (like CMV,. IgG rubella) , hepatitis serology , Pap smear . Thyroid, Rubella profile, IgM Toxo, Tests for N gonorrhoea (urethral discharge) , Chlamydia screening, Urine RS/CS, Whole abd USG . If affordable then  Serum Homocysteine 5<   (normal range is 6-14micro mol/Liter. 6, Vit B 12 , Serum Folate, Physician consulation if anorexia, Hepatomegaly, any dyspepsia, anorexia, wt loss .\Other special tets marked as Item A,(  Screening for acquired antiphospholipid antibodies (Thrombophilic screening) ,&  Item B(.)  Screening for inherited Thrombophilia)  . Other autoimmune screening  ( ANF, anti-dse DNA ab, Anti-mitochondrial ab & Anti Neurtophil cytoplasmic ab(ANCA) , Anti smooth ms ab . 4. Referral to a clinical geneticist, about 5% of RPL are due to translocations.

  

Item A:_Screening for acquired antiphospholipid antibodies (Thrombophilic screening) ,. Protein C, S and or antithrombin III Deficincy. There is an entity called seronegative APLA. SLE causes thrombosis of small placental vessels causing RPL/ IUFD . We have to remember that naturally circulating anticoagulants are 1) Protein C, 2) Protein S  & 3) Anti thrombin III. If there is  genetic defect of production of Protein C, or S or Antithrobin III then there  will be minimal natural anticoagulants in body. Tendency of hypercoagulable state.

 

Any added factor??  Such an procoagulant state may be accentuated by following 8 added factors like 1) age > 35 yrs 2)  Migraine   3) Past H/O VTE of causes unreeled to APLA   4) Hyper triglyceridaemia 5) , HHcst         6) DM with partly vascular damage
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3.)  Screening for inherited Thrombophilia,
(one should remember that APLA panel include following parameters e.g. A)   B2 glycoprotein-divvy, B)  dry Vat Lupus anticoagulant ( apt, DRW screen ) ,C) ACA ( Anti cardiolipin ab)  Cardiolipin antibody,=IgM ab (ACA):- may also cause IUFD, ,Unexplained subfertility, ) (Ig &IgM ab)-Negative means the IgG GPL units /illegal is < 10 GPL units /ml , But if persistently high( that is the label is high to 40 GPL) that has a real significance.

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& Paternal chromosome--any translocations??  6) Tests for APL ,One may ask what step to be adopted if  only DRVTT positive? Ans:- I feel that under such circumstances one should be prescribe  LMWH and (LDA).  May proceed for tests for secondary APLA or other autoimmune probality ( ANF, anti-dse DNA ab,  or inherited thrombophilia unless u work up completely u all not know or 80 percent of times v may get negative results . Simplest trial is preconception folic wad b 12 n ecosprin n wad UPT positive itself start heparin may b diff in such cases to reach ideal time to start heparin . Class 3 tests (contd):-Not evidence based tests for RPL but people quite often in insist on such, possibly meaningless, clinically irrelevant tests? Therefore such tests are optional :- 1) serum homocysteine (normal level is 6-14 µmol/Lit, , Serum Vit D & B12 level, 2

3) To relentlessly search for Chr. Nonspecific infn of uterus –Chlamydial screening, Mycoplasma culture,, Brucellosis, CMV screening, 4) Sperm-for Polyspermia( per sperm less DNA share à resulting into  Post implantation disorders), 5) Class 3 tests (contd):-Not evidence based tests for RPL but people quite often in insist on such,  Tests for Hypercoagulability-like less Protein C,(normal range of Pro C is 70-130 %of normal biological range- and Pro C is a cofactor for proteins, But this  range will be altered while someone is on Heparin  Ry ) :Protein-S deficiency (these two proteins C & S - are natural anticoagulants) –Normal value of Protein S is 55-122%of biological value   & raised ANTITHROMBIN III, 5) Class 3 tests (contd):-Not evidence based tests for RPL but people quite often in insist on such,  T Hysteroscopy for synechiae, anatomical defects of ut e.g. - small septum, polyp, slight duplications of ut, unicornate ut. Hysteroscopy also help us to rule out Koch's 6) Any subtle Endocrinopathy: - –autoimmune thyroiditis, PCOS women with androgen excess milieu, Poor Ov reserve (AFC, AMH), ERA tests-poor endometrial receptivity etc. Type I tests : Extrauterine factors  causing IUFD are more in number than intrauterine factors, which are like 1) synechiae, 2) septal disorders, 3) submucous Myoma-3D USG.

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