Intra uterine Foeatl death -How to investigate

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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5. & 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.

C)  What are the treatment modalities which are not agreed iniversally but often many member practice such methods: Trade off!!!   Such Treatments which, as I mentioned are   less evidence based though, admittedly many advocate such procedures (not talking if tests):- cervical cerclage may be associated with a high risk of minor morbidity but no serious morbidity.
• Heparin can be associated with maternal complications including bleeding, hypersensitivity reactions, and heparin-induced thrombocytopenia and, when used long term, osteopenia and vertebral fractures. Two prospective studies have shown that the loss of bone mineral density at the lumbar spine associated with low-dose long-term heparin therapy is similar to that which occurs physiologically during normal.

 Should we rule out autoimmune diseases in such cases? What test we should order to rule out this condition?

One  may use omnacortil in 1st trimester in idiopathic recurrent abortions   Steroids will cause Wundt put a possible xx fetus at risk of virilization?

Can we use steroids in unexplained IUFD with presumption of immune factor related previous foetal death?? Ans: omnacortil  may be used in rare occasions.  Some people are using immunoglobulin bharglobe  intramuscular injections weakly or fortnightly
Prior to conception and during first trimester

 In unexplained recurrent miscarriage, supportive care on its own can give good outcomes in upto 70 percent women. The problem with using treatment methods that are unproven is that the woman starts believing that she needs it in all future pregnancies and some of these treatments have not been studied well enough to ensure low risk of harm