BIOCHEMISTRY OF PREGNANCY

BIOCHEMISTRY OF PREGNANCY
Marked hormonal changes in the maternal circulation facilitate the metabolic, vascular and immunological adjustments necessary for the fetus to thrive. Abnormal concentrations of hormones or substances of fetoplacental origin may indicate gestational pathology.

BIOCHEMICAL DIAGNOSIS OF PREGNANCY

hCG Glycoprotein produced by the syncytio-trophoblastic cells of the placental villi Alpha & beta subunits Functions to:
Support secretion of progesterone by the corpus luteum until the placenta can produce enough hormone Promote steroidogenesis by the fetoplacental unit Promote gonadal development in the foetus

BHCG
BHCG detectable in maternal blood 7-9days after conception and in urine 1 2 days later. Latex agglutination technique detects >200IU/L High sensitivity blood immunoassays detect levels as low as 0.5 IU/ml Positive when hCG exceeds 25IU/L or if a lower concentration doubles within2 days.

BHCG
Also useful in estimating gestation with uncertain dates but USS is more accurate. hCG estimation advocated in diagnosis of early pregnancy

Low for gestation concentration and absence of intrauterine pregnancy on USS (?ectopic pregnancy) Values less than double the original highly suggestive hCG estimation also useful in diagnosis and monitoring of choriocarcinoma.

Other Tests of Pregnancy

Schwangerschaftsprotein 1
Glycoproteins of placental origin with no known physiological role. Proposed for determining gestational age in early pregnancy

Pregnancy Associated Plasma Protein A

Unclear origin but plays a role in immunosuppression in early pregnancy, complement inhibition and coagulation changes. Levels rise throughout pregnancy. Seems superior in predicting the outcome of threatened abortion. PAPPA levels reported to be consistently low in all cases of ectopic pregnancy.

Ectopic Pregnancy
Incidence seems to be on the increase. Variable symptoms & definitive diagnosis is by laparascopy. With high index of suspicion do preg test followed by a quantitative hCG.

Levels above 3000IU/ml indicate intrauterine sac in normal pregnancy which can be viewed by USS. Absence of a sac increases probability of an ectopic pregnancy (laparascopy).

Normally hCG levels double every two days and lesser rises noted in ectopic pregnancy.

Biochemical Monitoring of Pregnancy

Low levels of various hormones and placental proteins reported in early spontaneous abortions. (progesterone) Fetal Malformation Biochemical tests focus attention on high risk pregnancies so that appropriate diagnostic procedures can be carried out (USS)

Biochemical Monitoring of Pregnancy/AFP

Glycoprotein produced by hepatocytes and yolk sac of the foetus & spills into maternal circulation

Maternal AFP levels rise steeply at 16 weeks and decline after 32 weeks. Grossly elevated in neural tube defects, threatened abortion, infantile polycystic kidneys, bilateral renal agenesis. Routine screening for these usually done during second trimester. Serum AFP values also useful in adults in the diagnosis of hepatocellular carcinoma and teratoma of the testes.

Fetal Genetic Abnormality

USS detects majority of significant foetal structural abnormalities Tissue sampling for karyotyping a better indicator Risk factors include high maternal age (however only 30% of Down s)

Maternal Biochemical Screening (Triple test)

MSAFP and plasma oestriol concentrations reported to be lower in fetal Down s syndrome Maternal plasma BHCG levels were reported to be elevated in the same condition. The triple test is used together with maternal age and weight to calculate a risk score of the foetus having Down s syndrome. NB Not 100% predictive but allowsa better selection of candidates for definitive tests.

Fetal Tissue Sampling Techniques

Prenatal diagnosis of genetic abnormalities. Choice of sampling technique depends on gestation age.
Chorionic Villus Sampling Amniocentesis Fetal blood sampling

Biochemical Monitoring of Fetal Wellbeing

USS based biophysical tests of fetal well-being has resulted in a marked decline in the use of biochemical tests. Amniotic fluid AFP and acetylcholinestrase concentrations elevated in fetuses with neural tube or abdominal wall defects. Fetal lung maturity assessed by ratio of lecithin to sphingomyelin (Ratio greater than 2 indicates fetal lung maturity). Presence of phosphatidyl glycerol is however more definitive.

Biochemical Monitoring of Fetal Wellbeing

AF analysis also useful in determining severity of HDN through measurement of bilirubinoid pigments. Degree of elevation of absorbance peak at 450nm of amniotic fluid correlates with severity of erythroblastosis fetalis Intrauterine exchange transfusion

Biochemical Monitoring of Fetal Wellbeing

Placenta major source of oestrogens. Derived DHEA-SO4 from fetal adrenal glands, then converted to oestriol in the placenta and conjugated in the maternal liver. Assesses fetoplacental unit function Decreasing Oestriol and HPL levels indicate fetal distress. Affected by maternal hepatic and renal integrity. Drop of 40 50% below established mean early indicator of fetoplacental distress.

Gestational edema-proteinuriahypertension (GEPH)

Toxaemia of pregnancy refers to a group of disorders related to pregnancy. Concurrent oedema, proteinuria and hypertension define preeclampsia which can be followed by eclampsia characteristically manifesting as convulsions and coma 10% of patients with severe eclampsia develop the HELLP syndrome (haemolysis, elevated liver enzymes and low platelet count)

Biochemical Changes in Pregnancy

Oestrogen, progesterone, testosterone and prolactin increase throughout gestation whilst LH and FSH levels decrease. Levels of hormone binding globulins also increase. Use of usual reference ranges inappropriate in pregnancy (ALP, urea creatinine)

Biochemical Changes in Pregnancy

Total body water increases by 7litres (increased GFR) Pregnancy induces changes in plasma proteins due to: Non specific responses Changes in plasma volume Hormone induced protein synthesis & degradation. (TBG, SHBG, Caeruloplasmin, Transferrin Transaminases slightly increased with substantial increases in ALP

Biochemical Changes in Pregnancy

Trigs increased 2-3X by third trimester with Chol only marginally elevated Insulin resistance typical of pregnancy mediates changes in LDL & HDL (both increase and level off)

Biochemical Changes in Pregnancy

GDM: Carbohydrate intolerance of variable severity first recognised during pregnancy. Commonest complication is macrosomia due to hypersecretion of insulin by the foetus Insulin resistance induced by elevated sex hormones Pre existing IDDM results in increased exogenous insulin requirements and requires frequent monitoring with fructosamine. Majority of pregnant women develop glycosuria due lowered glucose threshold