Ferritin -What we need to know about it?

Q.1: What is Ferritin?? Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. In humans, it acts as a buffer against iron deficiency and iron overload. Ferritin is a blood protein that contains iron. Ferritin is a protein in the body which binds to iron. Most of the iron in the body is bound to ferritin, which is found in the bone marrow, liver, spleen and skeletal muscle.  A ferritin test helps us to understand how much iron ones has  body stores

Q.2: Which lead to low ferritin??   Ans: it implies that  Her  blood ferritin level is lower than normal, it indicates her body's iron stores are low and she is having  iron deficiency.   A result of low ferritin is strong evidence of an iron deficiency. . Most laboratories consider serum ferritin levels greater than 200 ng/mL in women and greater than 300 ng/mL in men to be abnormal. However, a large percentage of the general population has a serum ferritin level between 200 and 1,000 ng/mL(normal range). Serum ferritin levels are measured in medical laboratories as part of the iron studies workup for iron-deficiency anemia.^[5] The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. However, ferritin levels may be artificially high in cases of anemia of chronic disease where ferritin is elevated in its capacity as an inflammatory acute phase protein and not as a marker for iron overload.

Normal ranges[edit]

A normal ferritin blood level, referred to as the reference interval is determined by many testing laboratories. The ranges for ferritin can vary between laboratories but typical ranges would be between 30–300 ng/mL (=μg/L) for males, and 18–160 ng/mL (=μg/L) for females.

Normal ferritin blood levels according to sex and age[28]
Men	18–270 nanograms per milliliter (ng/mL)
Women	18–160 ng/mL
Children (6 months to 15 years)	7–140 ng/mL
Infants (1 to 5 months)	50–200 ng/mL
Neonates	25–200 ng/mL

Deficiency

If the ferritin level is low, there is a risk for lack of iron, which could lead to anemia.

In the setting of anemia, low serum ferritin is the most sensitive lab test for iron-deficiency anemia.^[29] However it is less specific, since its levels are increased in the blood by infection or any type of chronic inflammation,^[30] and these conditions may convert what would otherwise be a low level of ferritin from lack of iron, into a value in the normal range. For this reason, low ferritin levels carry more information than those in the normal range.

Low ferritin may also indicate hypothyroidism, vitamin C deficiency or celiac disease.

Low serum ferritin levels are seen in some patients with restless legs syndrome, not necessarily related to anemia, but perhaps due to low iron stores short of anemia.

A falsely low blood ferritin (equivalent to a false positive test) is very uncommon, but can result from a hook effect of the measuring tools in extreme cases.^[33]

Vegetarianism is not a cause of low serum ferritin levels, despite the common myth. The Position of the American Dietetic Association pointed this out in 2009 stating, “Incidence of iron-deficiency anemia among vegetarians is similar to that of non-vegetarians. Although vegetarian adults have lower iron stores than non-vegetarians, their serum ferritin levels are usually within the normal range

Excess

If ferritin is high, there is iron in excess or else there is an acute inflammatory reaction in which ferritin is mobilized without iron excess. For example, ferritins may be high in infection without signaling body iron overload.

Ferritin is also used as a marker for iron overload disorders, such as hemochromatosis or hemosiderosis. Adult-onset Still's disease, some porphyrias, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome are diseases in which the ferritin level may be abnormally raised. Mitochondrial ferritin has many roles pertaining to molecular function. It participates in ferroxidase activity, binding, iron ion binding, oxidoreductase activity, ferric iron binding, metal ion binding as well as transition metal binding. Within the realm of biological processes it participates in oxidation-reduction, iron ion transport across membranes and cellular iron ion homeostasis.

As ferritin is also an acute-phase reactant, it is often elevated in the course of disease. A normal C-reactive protein can be used to exclude elevated ferritin caused by acute phase reactions.

Ferritin has been shown to be elevated in some cases of Covid-19 and may correlate with worse clinical outcome.  According to a study of anorexia nervosa patients, ferritin can be elevated during periods of acute malnourishment, perhaps due to iron going into storage as intravascular volume and thus the number of red blood cells falls. Another study suggests that due to the catabolic nature of anorexia nervosa, isoferritins may be released. Furthermore, ferritin has significant non-storage roles within the body, such as protection from oxidative damage. The rise of these isoferritins may contribute to an overall increase in ferritin concentration. The measurement of ferritin through immunoassay or immunoturbidimeteric methods may also be picking up these isoferritins thus not a true reflection of iron storage status

·         . Q. 3: Which lead to high ferritin?? If a ferritin test shows higher than normal levels, it could indicate that she has a condition that causes body to store too much iron. It could also point to liver disease, rheumatoid arthritis, other inflammatory conditions or hyperthyroidism. Ferritin concentrations increase drastically in the presence of an infection or cancer. Endotoxins are an up-regulator of the gene coding for ferritin, thus causing the concentration of ferritin to rise. By contrast, organisms such as Pseudomonas, although possessing endotoxin, cause plasma ferritin levels to drop significantly within the first 48 hours of infection. Thus, the iron stores of the infected body are denied to the infective agent, impeding its metabolism.

·         Hemochromatosis

·         Porphyria — A group of disorders caused by an enzyme deficiency that affects your nervous system and skin

·         another chronic inflammatory disorder

·         Hyperthyroidism

·         Leukemia

·         Hodgkin's lymphoma

·         Multiple blood transfusions

·         Alcohol abuse

·         Taking too many iron supplements

If a ferritin test shows higher than normal levels, it could indicate that she have a condition that causes her  body to store too much iron.. Many laboratories consider serum ferritin levels greater than 200 ng/mL in women and greater than 300 ng/mL in men to be abnormal. As mentioned normal value is However, a large percentage of the general population has a serum ferritin level between 200 and 1,000 ng/mL.

.

Results

The normal range for blood ferritin is:

·         For men, 24 to 336 micrograms per liter

·         For women, 11 to 307 micrograms per liter

In humans, it acts as a buffer against iron deficiency and iron overload. Ferritin is found in most tissues as a cytosolic protein, but small amounts are secreted into the serum where it functions as an iron carrier. Plasma ferritin is also an indirect marker of the total amount of iron stored in the body; hence, serum ferritin is used as a diagnostic test for iron-deficiency anemia. Ferritin serves to store iron in a non-toxic form, to deposit it in a safe form, and to transport it to areas where it is required. The function and structure of the expressed ferritin protein varies in different cell types. This is controlled primarily by the amount and stability of messenger RNA (mRNA), but also by changes in how the mRNA is stored and how efficiently it is transcribed.  Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species via the Fenton reaction. Hence vertebrates have an elaborate set of protective mechanisms to bind iron in various tissue compartments. Within cells, iron is stored in a protein complex as ferritin or the related complex hemosiderin.

 Apoferritin binds to free ferrous iron and stores it in the ferric state. As ferritin accumulates within cells of the reticuloendothelial system, protein aggregates are formed as hemosiderin. Iron in ferritin or hemosiderin can be extracted for release by the RE cells, although hemosiderin is less readily available. Under steady-state conditions, the level of ferritin in the blood serum correlates with total body stores of iron; thus, the serum ferritin FR5Rl is the most convenient laboratory test to estimate iron stores.

Ferritin is a globular protein complex consisting of 24 protein subunits forming a nanocage with multiple metal–protein interactions. It is the primary intracellular iron-storage protein in both prokaryotes and eukaryotes, keeping iron in a soluble and non-toxic form. Ferritin that is not combined with iron is called apoferritin.

Ferritin gens:-In human ferritin, introns are present between amino acid residues 14 and 15, 34 and 35, and 82 and 83; in addition, there are one to two hundred untranslated bases at either end of the combined exons. The tyrosine residue at amino acid position 27 is thought to be associated with biomineralization.

Ferritin is a hollow globular protein of mass 474 kDa and comprising 24 subunits. It is present in every cell type. Typically it has internal and external diameters of about 8 and 12 nm, respectively.  The nature of these subunits varies by class of organism

H pylori is a common cause of iron resistant anemia

 How many members believe that H Pylori infestation is not an uncommon cause of Fe deficiency anemia in pregancy by impairing Fe absorption from duodenum? But, for confirmation of such diagnosis upper G I endoscopy is essential. Is that  true? If confirmed in pregancy period what % of Fe resistant anemia may be attributed  to  H Pylori infection in our country? Any guess??  What is the drug that will be most effective for such diseases, pregnancy period in particular? Have anybody ever prescribed amoxicillin or Metrogyl based on persistent symptom complex of  combination of dyspepsia and Fe resistant anemia?

What is  H Pylori?? How it causes abnormalities in gastro duodenal normal function? Helicobacter pylori is a ubiquitous gram-negative bacterium infecting half the world's population and causing chronic active gastritis in virtually all infected individuals. The majority of individuals who acquire chronic H pylori gastritis will exhibit mild gastritis, more prominent in the antrum compared with the corpus. A minority of infected patients develop marked chronic inflammation in the antrum, with mild inflammation in the oxyntic mucosa (antral-predominant gastritis), and are prone to develop duodenal ulcer.  

How it causes gastric Cancer??  Ans:-Infrequently, some individuals show a corpus-predominant pattern that overlaps with autoimmune gastritis. Recently, epidemiologic and laboratory studies in animals as well as interventional studies in humans strongly suggested that H pylori may play a pathogenic role in the development of adenocarcinoma of the distal stomach. In particular, individuals with corpus-predominant gastritis seem more susceptible to development of adenocarcinoma of the distal stomach. The mechanisms whereby H pylori may cause gastroduodenal disease and contribute to gastric carcinogenesis are still hypothetical .

How useful is commonly used reasonably safe is metronidazole?? Ans: However, the production of specific virulence factors by the bacterium, the inflammatory response of the host, and the association with environmental factors may all play a contributory role

How useful is Metronidazole ??  Ans:- . H pylori is generally highly sensitive to metronidazole, which is actively secreted into gastric juice and saliva, with activity independent of pH.  I believe this can be prescribed empirically in pregancy after 20 weeks. Metronidazole is a prodrug that must undergo activation by bacterial nitroreductases. There are a number of H pylori enzymes with the potential to reduce metronidazole, and it is possible that increased drug dosage and resulting very high concentrations in the stomach allow sufficient drug to become activated to kill the organism. Reduced nitroimidazoles (eg, metronidazole) cause loss of the helical structure of bacterial DNA, strand breakage, and thus, impairment of bacterial function.

Can we empirically use Amoxicillin in Fe resistant anemia, pregancy period in particular ??

Amoxicillin is a close chemical and pharmacologic relative of ampicillin. This agent is stable in acid and inhibits the synthesis of the bacterial cell wall, acting both topically and systemically after absorption into the bloodstream and subsequent delivery into the gastric lumen. H pylori demonstrates good sensitivity to this antibiotic in vitro, but gastric antisecretory cotherapy is required for any significant efficacy.

What about Clarithromycin in nonpregancy period ?

Clarithromycin, a 14-membered ring macrolide antibiotic, is a derivative of erythromycin, with a similar spectrum of activity and clinical application. However, clarithromycin is more acid-resistant, has more consistent absorption, and has a longer elimination half-time compared with erythromycin. Results of studies showing approximately 90% H pylori  eradication with triple-therapy regimens using clarithromycin have led to widespread use of this antibiotic. However, the increasing prevalence of clarithromycin-resistant H pylori strains must be kept in mind before using this antimicrobial agent. In this setting, unlike the situation with metronidazole, there is no evidence that increasing the dosage of drug will overcome the problem of bacterial resistance.

Tetracyclines

The tetracyclines are close derivatives of the polycyclic naphtacenecarboxamides. The site of action of tetracyclines is the bacterial ribosome, which results in the interruption of protein biosynthesis — but at least 2 processes appear to be required for these antibiotics to gain access to the ribosomes of gram-negative bacteria. The first of these is their passive diffusion through hydrophilic pores in the outer cell membrane. The second process involves an energy-dependent active transport system that pumps all tetracyclines through the inner cytoplasmic membrane. Once the tetracyclines gain access to the bacterial cell, they inhibit protein synthesis and bind specifically to the 30-S ribosomal subunit. The latter thereby prevents aminoacyl tRNA access to the acceptor site on the mRNA-ribosome complex, and thus precludes the addition of amino acids to the growing peptide chain. Tetracycline has demonstrated in vitro efficacy against H pylori and is active at low pH.

Dose of intravenous Inj FCM as IV therapy-How much Inj FCM is too much??

Any member using 1500 mg Inj FCM  as a single dose eiher in puerperium or women with menorrhagia with moderate to severe anemia with documented low serum Fe, low Ferritin and high TIBC?? ??

Iron is an essential element and its balance must be maintained for proper physiologic functioning. Blood loss, a major cause of iron deficiency, is highly prevalent  A) women  with menorrhagia left untreated for long time B) patients with chronic occult gastrointestinal (GI) blood .However, there is no point in denying that therapeutic management of IDA is focused primarily on repletion of iron stores . While iron deficient individuals without inflammation may respond to oral iron therapy, administration of IV iron is beneficial in many patient populations, including those with inflammation resulting, from variety of   systemic diseaes., from kidney disease, heart failure, or rheumatological diseases, patients who cannot tolerate oral iron, and patients who are noncompliant with oral iron therapy

Iron intolerance :-Even under the best of circumstances, oral iron is not well tolerated, and patients are often nonadherent for a variety of reasons, including intolerable side effects and the need for multiple daily doses .The frequently poor absorption of oral iron, moreover, can contribute to suboptimal patient response.

The hepcidin response in anemic patients having inflammatory conditions, such as inflammatory bowel disease (IBD), inhibits GI absorption of oral iron .Moreover, hepcidin impacts iron homeostasis in patients with concurrent inflammation (e.g., repressed recycling of iron from the reticuloendothelial system and sequestration in bone marrow); this may limit both oral and IV iron supplementation and may serve to explain why such patients remain iron deficient despite multiple courses of therapy . Despite these recommendations, in many clinical situations the treatment of IDA with IV iron has not been limited to a cumulative dose of 1000 mg. In oncology patients, for example, the National Comprehensive Cancer Network (NCCN) states that if the calculated dose exceeds 1000 mg, the remaining dose may be given after 4 weeks if the Hb response is inadequate Additionally, in two randomized controlled trials involving IV iron supplementation in oncology patients, a total of up to 3000 mg iron was administered in weekly doses of 100 mg . In another prospective, randomized, controlled trial, patients with chemotherapy-related anemia received cumulative doses of IV iron ranging from 1000 to 3000 mg .

Q.1. What is the consensus of the most appropriate iron deficit repletion dosing in patients with IDA.  Ans:   Currently, there is no consensus regarding the most appropriate iron deficit repletion dosing in patients with IDA, partly because the iron dosing selected for virtually all trials has been based largely on clinical judgment, clinical guidelines in nephrology, or best estimates from past results . But is it possible to administer of a higher cumulative dose of IV iron than what is typically administered, with the goal of providing clinicians with practical, evidence-based guidance for determining iron dosing requirements in a wide range of patients with IDA. 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS). 

Guidelines for the management of IDA in inflammatory bowel disease (IBD), moreover, recommend IV iron as the preferred route of administration and state that anemic IBD patients rarely present with total iron deficits below 1000 mg. These guidelines recommend use of the Ganzoni formula to estimate iron replacement needs, and in controlled trials, up to 3600 mg of iron sucrose has been administered safely (up to TSAT >50%) .  Congruent with evidence reported in the international IBD guidelines, many states that cumulative doses up to 3600 mg of IV iron may be administered safely in these patients(IBD cases) .

Q. 2: The classification of types of iron complexes used in I V route??  Ans: The reactivity of each complex correlates inversely with its molecular weight; larger complexes are less prone to release significant amounts of labile iron or react directly with transferrin .Type I complexes such as iron dextran preparations or FCM have a high molecular weight and a high structural homogeneity and thereby deliver iron from the complex to transferrin in a regulated way via macrophage endocytosis and subsequent controlled export . To help determine the optimal means of administering these higher doses, it is important to note that the degradation kinetics, and therefore the safety, of parenteral iron products are directly related to the molecular weight and stability of the iron complex

Complexes can be generally classified as A) labile or B) robust (kinetic variability, i.e., how fast the ligands coordinated to the iron can be exchanged) and weak or strong (thermodynamic variability, i.e., how strongly the ligands are bound to the iron and thus how much energy is required to dissociate a ligand from the iron) or any intermediate state

 They also bind iron tightly as nonionic polynuclear iron(III) hydroxide and do not release large amounts of iron ions into the blood. Such complexes can be administered intravenously and are clinically well tolerated even when administered at high doses. For less stable iron complexes, the maximum single doses are significantly lower and the administration times are drastically longer

Q. 4. What is FCM?? Ans: FCM is a stable type I polynuclear iron(III) hydroxide carbohydrate complex that prevents the partial release of iron to serum ferritin observed with IS(iron sucrose) , allowing administration of high doses, since this iron is available only via reticuloendothelial processing .

FCM can be administered as a single 750 mg dose via a slow IV push injection over 7.5 minutes or as an IV infusion over at least 15 minutes. The second dose is administered at least 7 days later for a recommended cumulative dose of 1500 mg iron. But use of high doses reduces the number of infusions, enabling the possibility of cost reductions compared to multiple administrations

Q. 5. Can we administer I V iron in Cancer related anemic patients?? Many also believe that more routine use of IV iron for CRA(Cancer-related anemia )  and chemotherapy-induced anemia (CIA Cancer-related anemia ) is appropriate in view of existing evidence. Oncology patients whose CIA is treated with ESAs, furthermore, respond better to IV iron therapy than to oral supplementation . Mixed anemia is a diagnosis of exclusion without a therapeutic trial of iron.

Q. 6. Can we administer 1500 mg Inj FCM  in severe Fe deficient men/ wmen to avoid repeated visits?? I V iron in higher doses??  Recently few researchers have suggested that suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in the majority of patients with IDA and that a dose of 1500 mg is closer to the actual iron deficit in these patients. Additionally, 1500 mg of iron resulted in a more rapid, robust Hb response, allowed more patients to reach target Hb levels, and required a longer mean time to retreatment with additional IV iron compared to 1000 mg of iron. They belive that 1500 mg of IV iron is more suitable for iron repletion in many patients with IDA compared to the commonly utilized dose of 1000 mg of IV iron. . In some studies  multiple-dose, phase II/III study of IDA patients with GI disorders, mean total cumulative doses of 1800 mg IV iron were administered /Clinical evidence also indicates that iron requirements of 1000 to 1500 mg or higher may be required in patients with NDD-CKD to attain target ferritin and Hb levels, up to 1600 mg may be required in obstetric patients, and as much as 2000 mg may be needed in patients with heavy or abnormal menstrual bleeding

Clomiphen resistance

  Is 100 mg enclomiphene better than commonly prescribed Zu+En combination?  Members prescription preference ??

Enclomiphene resistant/ Clomiphene resistant : How to proceed :      It often happens that a 28 yr old woman , PCOS with normal Hormonal profile and had two courses of ovulation induction done by  100 mg enclomiphene. What is the next practical approach-but in folliculometry there was no ovulation. Next step, according to me will be as follows :members may suggest their own views liberally as this page is “ a sharing of knowledge and wisdom.’-:- Weight loss,& CC+ low dose step up Gonadotrophins protocol works better.

Supplement with  HMG on the last day of CC: Adding CC to GT reduces cost In addition to  addressing  weight management, she can be advised  Traditional CC (Zu+En)  combination as 50 or 100mg  from day 2 or 3 for 5 days. To start GT(Gonadotrophins)  (u-FSH or r-FSH) 50-75 IU on the last day of CC or a day after the last dose of CC, daily and follow her up with alt day folliculometry and watch for response after 3-4 days. If maximum 3-4 lead follicles then such supplemtation of hMG in midfolicular phase is beneficial. Therefore, If failed to ovulate with CC alone next best step will be  CC + Gonadotrophins at low dose with step up is a good option if she has failed to ovulate. If maximum 3-4 lead Follicles seen recruited, gradually step up Gonadotrophin dose, or remain same and reassess, hCG trigger can be given when lead follicle is beyond 18mm.

3)  Chronic low dose step up protocol :--Avoid using CC further after 4 cycles if no ovulation. One can consider  chronic low dose step up protocol in such CC –Gonadotrophin resistant cases ("non-responders") after estimating AMH, AFC and HSG if not doe earlier ,If that too fails to induce ovulation . - In chr. low dose step up, one should  start with daily injection of Gonadotrophin at 37.5 IU only, say up to 7 or even 10 days. Then on day 11 of stimulation document for response and either increment slowly or keep the same. To administer hCG at +18mm..

4) to consider Lap-Hyst with mind set for LOD as well (drilling) . --> followed by IUI + OI. Buy little time and give them enough time as trying time is less.

5) GnRH analogue? Not commonly used.

6)  LOD : But it must be explained to the couple and relative about the drawbacks of LOD about possible decrease of ovarian reserve. Therefore, resort to LOD as a last option. It may utmost decrease the OHSS severity in case of IVF. Chief Indication of LOD:--To document  FSH AND LH on day 2 , if LH >2 times FSH , counsel the  pt for drilling , if pt not willing one  can try with 150 mg cc , may  occasionally have god result specially with added   Metformin .

7) Inositol, once upon a time such  were classified in the B-Complex group of vitamins and still considered a nutritional adjuvant, mostly derived  from plants. Mode of action is not very clear, but helps to control hunger "centre" as well. Many scientists still don’t consider as a "drug" for PCOS, but they consider inositols as any “vitamin-like adjuvant.

8) Vit D is an "in-vogue" drug. No harm giving in moderate dose, though hypervitaminosis is a rare known.

 (9)  May use Use R-FSH instead of HMG in PCOS cases with high LH: - on day 7/day 8: As mentioned earlier to cut cost of r-FSH one can start “clomiphene 100 for 5 days followed by u-FSH from 7 th day onwards. Therefore to prescribe 100 mg cc from day 2 to day 6. Then inj u-FSH 75 IU on day 7, 8, 9.” < but occasionally such low cost policy don’t work. That is why some ART specialists are switching over to r-FSH which is costlier on the plea that  she is pcos, high LH may yield better results. But there is disagreement on this issue,& IUI 

Doppler of Cerbroplacental Ratio

The gaining  popularity of Doppler studies in antenatal foetal surveillance :-?? . Doppler informations   play an important role in the surveillance of uncomplicated prolonged pregnancies. The most common reason given for routine labor induction is that current fetal surveillance tests cannot accurately identify which pregnancies are at risk for an adverse outcome. Many, therefore recommend that further newer tets of antenatal surveillance are necessary which are more accurate to assess the effectiveness of the antenatal fetal testing..

A) How informative is Umbilical artery Doppler?? Ans:-Most authors have shown that increase in fetal umbilical resistance index in prolonged pregnancies is related to an increase in the adverse perinatal outcome. Buy many don’t agree and their argument is that placental aging is  not related to an increase in the resistance of the fetal umbilical artery (UA) and that most prolonged pregnancies with adverse outcome had normal umbilical artery resistance values.

2. Middle cerebral artery (MCA) resistance is known to A) decrease at the end of pregnancy. This may represent a physiological change associated with an increase in cerebral metabolic requirements, --a brain‐sparing effect to protect intracranial structures during labor  or secondary to a mild degree of placental insufficiency.

A ratio of MCA to UA, the cerebroplacental ratio (CPR), has been proposed as a better predictor of fetal compromise than either vessel considered alone, even when umbilical resistance index is within normal range. This is thought to be because the CPR evaluates the fetal hemodynamics and quantifies redistribution of cardiac output better than the umbilical or the cerebral flow alone. The good sign is :- Reference ranges for umbilical and middle cerebral artery pulsatility index and cerebroplacental ratio in prolonged pregnancies. To construct normal ranges for umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI) and cerebroplacental ratio (CPR) in prolonged pregnancies according to strict methodological criteria using polynomialàThe cerebro-umbilical (MCA PI/UA PI) and cerebro-uterine (MCA PI/Uterine artery PI) ratios were calculated. Both the cerebro-umbilical are cerebro-uterine ratios were found to be higher in female fetuses (1.74 vs. 1.81 and 1.95 vs. 2.1 respectively) but this difference did not reach statistical significance (p = 0.10 and 0.09 respectively).

Bad Signs are of MCA PSV-à:- at MCA/ PI it's 0.78,,Below 5 th centile for gestational age. But there is increase in MCA-PI before fetal demise. That means cerebral circulation is adapting to deoxygenating.. This pattern was independent of Umbilical Artery blood flow. None of these fetuses died. An increase in MCA-PI before fetal demise have been used to support possible intervention. But this statement is not true in very preterm foetus when these statements don’t hold good. in very preterm fetuses with SGR.. .

. Nomograms for UA and MCA pulsatility.Doppler examinations were performed by two examiners. For each examination, the mean value of three clear consecutive waveforms was recorded. 1) UA PI obtained from a free loop of the umbilical cord; (2) MCA PI measured in the straight portion of the artery avoiding head compression by the transducer and (3) the CPR was derived as a simple ratio of the MCA PI divided by the UA PI.

Doppler study of cerebroplacental Ratio

What is Obstetric relevance of Doppler values of Cerebroplacental Ratio ?? Q. What is best Doppler study to point out detection of foetal compromise?? Ans: Early detection of abnormal blood flow redistribution patterns is important for efficient fetal Doppler monitoring and is part of meticulous surveillance, with a potential benefit to reduce fetal morbidity and mortality.

Q.2: What is the relevance of CPR(cerebroplacental Ratio?? Ans:-We know that by the term CPR we understand “the ratio between the fetal umbilical artery pulsatility index (UA-PI) and the middle cerebral artery pulsatility index (MCA-PI)”., This ratio is called by sonologists as cerebroplacental ratio (CPR).

Q.3: What does this represent?? What CPR warns us?? Ans:-The CPR(the ratio) represents fetal blood flow redistribution at the early stages of placental insufficiency; Moreover, it has predictive value for adverse intrapartum and neonatal outcomes.

Q 4:-What is the normal curve like in normal pregnancies?? The MCA-PI and CPR values show a similar parabolic curve during the third trimester of pregnancy, with a peak value at 32 and 33 gestational weeks, respectively. The UA-PI showed a linear and gradual decrease over the gestational age.This is the key message that should be in our mind.

The UA-PI, MCA-PI, and CPR reference ranges were reconstructed for each of the vessels for each gestational age between 29 and 41 weeks.

Q.5:-Is it true that: “Fetal adequate blood flow circulation is mainly dependent on normal placental anatomy” ?? Ans: Mostly . But Doppler changes also partly depend on other developmental during pregnancy though an abnormal or malfunctioning placenta can directly affect fetal circulation.

Q.6:-What may go wrong if there is placental bed resistance –which may occasionally cause severe FGR & IUFD ??

Sequence 1:-The umbilical artery (UA) is usually the first fetal blood vessel to be affected by placental insufficiency. The initial increase in placental blood flow, vascular impedance, causes a retrograde increase of blood flow resistance in the UA. decrease in UA-PI represents a process of placental adaptation to the increasing fetal needs for oxygen supply with a steady decrease in blood vessel resistance during the third trimester of pregnancy.

Sequence 2:- Second vascular marker in the cascade of placental insufficiency There is a decreased middle cerebral artery pulsatility index (MCA-PI):-, When placental insufficiency further deteriorates, blood flow resistance in the descending aorta increases, resulting in more blood diverted through the aortic isthmus shunt to reach the fetal brain. This phenomenon is reflected by a decreased middle cerebral artery pulsatility index (MCA-PI), This fall of MCA-PI is an warning sign of second vascular marker in the cascade of placental insufficiency.

However, internationally accepted reference ranges for CPR are lacking.

Like