Biochemical changes in pregnancy

Adaptive changes in pregnancy

◦ Weight gain around 12 kgs due to : increases maternal fluid retention, increased maternal fat stores and due to
products of conception.
◦ 10-20% increase in basal metabolic rate by 3 rd trimester.
◦ Extra calories required ~ 300 kcal/ day
◦ Pregnancy is a major endocrine event.

Placenta
 Placenta is created from trophoblasts of blastocyst
 It links fetus and mother
 Has Different Functions:
◦ Keeps the maternal and fetal circulation systems separate
◦ Nourishes the fetus
◦ Eliminates fetal wastes
◦ Produces hormones vital to pregnancy

For substances to move from the maternal circulation to the

fetal circulation, they must cross through the trophoblast
cells and several membranes. The transfer of any substance
depends largely on the (1) concentration gradient between
the maternal and fetal circulatory systems, (2) presence or
absence of circulating binding proteins, (3) lipid solubility of
the substance, and (4) presence of facilitated transport, such
as ion pumps or receptor-mediated endocytosis. The
placenta is an effective barrier to the movement of large
proteins and hydrophobic compounds bound to plasma
proteins. Maternal immunoglobulin G (IgG) crosses the
placenta via receptor-mediated endocytosis. Because of its
long half - life, maternally produced IgG protects a newborn
for the rest 6 months of life. IgG antibody assays with low
limits of detection may be positive in infants up to age 18
months because of maternal antibodies.

Endocrine and hormonal changes

• Placental hormones
• Thyroid function
• Glucose and insulin

Placenta hormones
 Placental hormones:
 Protein hormones
◦ Human chorionic Gonadotropin (hCG)
◦ Human placental Lactogen (hPL)
 Steroid Hormones
◦ Progesterone
◦ Esteradiol
◦ Estriol
◦ Estrone
Human chorionic gonadotropin (hCG)
 • Produced by trophoblast (the developing placenta)
• As LH, FSH, and TSH, it is a glycoprotein composed of alpha and beta subunits
• Beta subunit of hCG is very similar to beta subunit of LH, but is longer
• The B chain is measured in the immunoassay (qualitative and quantitative measurements,
immunochromatography and immunometric respectively)
• Detected in blood 7-9 days after conception (once implantation occurs) at level >5 IU/L
• Detected in urine 8-11 days after conception at level 25IU/L.
• In normal pregnancy, plasma concentration doubles every two days.
• Secretion of BhCG peaks at 8-10 weeks and then starts to decline at the end of 1 st trimester.
• Cause enlargement of corpus luteum and ensure uninterrupted progesterone production until placenta provides
sufficient amount to maintain pregnancy.
• Clinical applications of hCG measuring:
◦ Screening and diagnosis of Pregnancy
◦ Abortion
◦ Ectopic Pregnancy
◦ Trophoblastic Tumors
◦ Risk of down syndrome and trisomy 18

Human placental lactogen (hPL)

• It is a single polypeptide hormone synthesized by trophoblasts cells
• It is very similar to GH and to a lesser extent to PRL
• It is detectable in maternal plasma after 8 weeks of gestation.
• It has lactogenic, metabolic, somatotropic, leuteotropic and erythropoietic effects.
• It decreases the effect of insulin and increase lipolysis and FFA.
• Was used to assess the like hood of threatened miscarriage and monitor late pregnancy but now is rarely used.

Steroid hormones
• Synthesis of steroid hormones increases during pregnancy
• The corpus luteum secrets large amounts of estrogen and progesterone, but after six weeks the placenta
becomes the major source.
• Estrogens and progesterone are needed for appropriate development of endometrium, uterine growth,
adequate blood supply and preparation of uterus for labor.
• The rise in their concentration contributes to many changes in the body.
• Estradiol reaches up to 100 fold in the 3rd timester.
• Sex hormone binding globulin (SHBG) levels increases 5 times during pregnancy.
• Estrogen synthesis is differ from that produced by ovaries in non pregnant female, as the placenta has no 17 -
hydroxylase.
• Esteriol is made from 16-OH DHEA-S produced by fetus liver
Thyroid function
• Usually euthyroid stat
• Increase thyroid binding globulin >> total T4, T3
• Free T4, T3 increase slightly in early pregnancy ( due to thyrotrophic effect of hCG), but later fall to normal.
• TSH fall in early pregnancy then return to normal
• 0.2% develop hyperthyroidism & 2% hypothyroidism
• hCG and TSH has identical alfa subunit and this explain why hCG has thyroid stimulating activity

Other hormonal changes:

Increases  ACTH, Cortisol, Prolactin, Aldosterone, Renin, Insulin, Glucagon
Decreased  LH and FSH

………………..
Carbohydrates metabolism
• Shift from glucose as source of energy to lipids.
• Fasting plasma glucose concentration falls slightly
• Postprandial concentration increases
• Deterioration in glucose tolerance due to insulin resistance induced by elevated concentration of sex hormones,
hPL and placental GH.
• Hyperinsulinemia
• In pre-existing type 1 diabetes mellitus, the requirement for exogenous insulin might increase.
• Pregnant with glucose intolerance may revert to normal glucose tolerance after delivery or develop diabetes.
• That is way glucose tolerance should be checked 6 weeks after delivery.

Lipids
• There will be hyperlipidemia
• Increase in lipolysis and decrease lipoprotein lipase
• Increase in total serum lipid concentration from the end of 1st trimester and reaches up to 40% at term.
• All components increase ( triglycerides rise 2-3 times, less increase in total cholesterol, phospholipids, and
free fatty acid(
 • This is due to rise in LDL and HDL
• Hyperlipidemia of pregnancy is influenced by oestradiol, progesterone, insulin and hPL.
• Hyperlipidemic state: increase in lipids, lipoproteins and apolipoprotein

• After delivery all decreases, inducing by lactation.

Renal
• Renal plasma flow and GFR increase up to 50%
• GFR reaches to about 170 mL/min/1.73 m2 by 20 weeks, and therefore increases in the clearance of urea,
creatinine, and uric acid
• Concentrations of these three analytes are slightly decreased in serum.
• Pregnant women should be tested for presence of glucose and proteins in urine.
• Glycosuria:
o Majority of pregnant women will have glycosuria at some stage of pregnancy due to lowered renal
threshold.
o Renal glycosuria should be differentiated from pregnancy aggravated diabetes melitus.
o Increased excretion of glucose, up to 1000 mg/d, may occur owing to increased GFR, which presents more fluid
to the kidney tubules and therefore lowers the renal glucose threshold.

o Renal glycosuria: they have glucose in the urine despit normal blood level , and only the form of sugar is glucose.
In pregnancy it results from pre existing deficiency in tubular function that is aggravated during pregnancy.

Proteinuria can be an early sign of preeclampsia

◦ Preeclampsia: Proteinuria (protein excretion of ≥ 300 mg in a 24 h urine collection, or a dipstick of ≥ 2+)

Proteins
◦ Pregnancy induces changes in protein concentration due to changes in plasma volume and specific hormone-
induced changes in protein synthesis and degradation.
◦ Total protein slightly reduced
◦ Cortisol concentration increases, and as a catabolic hormone, it causes mobilization of AA from muscle proteins
and stimulate uptake of AA by the liver and induction of enzymes required for gluconeogenesis.
◦ Albumin level falls approximately 15%
◦ Concentration of plasma transport proteins, globulins (e.g. SHBG) and acute phase proteins increase
◦ CRP remains unchanged but rise up to 4 fold in first two days post partum.

◦ 2-3 fold increase in 1 antitrypsin, fibrinogen and cerulosplasmin in the later stages of pregnancy.
◦ Plasma immunoglobulins not changed.
◦ ALP increases, reaching a peak of 2-3 times normal during 3rd trimester.
◦ Transaminases slightly increase
◦ Important causes of acutely elevated transaminases in pregnancy include : preeclampsia (HELLP syndrome),
acute fatty liver of pregnancy, cholestasis of pregnancy, viral and autoimmune hepatitis, drug reactions and
sepsis.
◦ ALP increases, reaching a peak of 2-3 times normal during 3 rd trimester due to presence of the placental
isoenzymes in maternal plasma, as well increase in bone isoenzymes in 3 rd trimester

◦ Acute fatty liver of pregnancy (read about it)  Life-threatining hypoglycemia may occurs. If untreated,
fulminant hepatic failure with hepatic encephalopathy results. Treatment is immediate termination of
pregnancy.

Alpha fetoprotein (AFP)

• It is glycoprotein synthesized mainly in fetal yolk sac and liver.
• It is the major protein in fetal serum.
• Normally it presents in very low concentration in the serum of healthy men and non pregnant women.
 • The normal concentration of AFP in maternal circulation varies from 20 to 100 ug/L and reaches the highest
concentration at 30 weeks of gestation.
• Causes of high maternal AFP:
o Neural tube defects
o Atresia of GIT, exomphalos
o Serious fetal abnormalities
o Multiple pregnancy
• Causes of low maternal AFP:
o Down’s syndrome
o Trisomy 18

Electrolytes
◦ Concentration of electrolytes slightly reduce due to hemodilution effect.
◦ Plasma osmolality also decreases from around 290 to about 280 mOsm/L.
◦ This decrease is mostly in the first trimester.
◦ There will be sodium and potassium retention.
◦ Severe hyponatremia is seen in preeclampsia
◦ Total Ca reduced but ionized un changed, urine excretion increases 2-3 times due to increase Ca absorption and
increase GFR.
◦ Phosphate slightly decreased
◦ Magnesium: serum level declines in 3rd trimester by 30 %., urine excretion increases.
◦ oestrogen and progesterone increasing sodium reabsorption in the proximal nephron and progesterone acting
as a mineralocorticoid antagonist in the distal nephron. 39 There continues to be conjecture concerning the
mechanism for fine control of potassium homeostasis during pregnancy.

◦ Serum potassium (K) is approximately 0.3 mmol/l lower in the third trimester compared with pre-pregnancy. 3–4

Blood gas
◦ Increase in minute ventilation driven by progesterone and 20% increase in oxygen consumption , but PO2
maintained constant.
◦ Slight decrease in PCO2 and results in a respiratory alkalosis which is fully compensated by renal bicarbonate
excretion.
◦ Bicarbonate levels are 25% lower in pregnancy

Others
◦ Iron :
◦ serum ferritin drops progressively from the 1 st trimester.
◦ Iron level stable or slight increase
◦ Transferrin increases by 10%
◦ Transferrin saturation falls slightly
◦ Transferrin iron binding capacity increase progressively
◦ Vit D : increase in 1, 25 OH vit D (due to effect of PTHrP and estrogen) , but 25 OH vit D not changed
◦ B 12: TOTAL B12 decrease due to reduction in holohaptocorrin , but active B12 ( holotranscobalamin) remains
unchanged and used as guide for B12 deficiency in pregnancy.