Biochemical changes in pregnancy

Biochemical changes in pregnancy, Physiological changes in pregnancy, maternal and fetal health assessment, assessment of complications in pregnancy, hormonal changes and physiological evaluations in pregnancy

1. Biochemical changes in pregnancy DR. OFONMBUK UMOH REGISTRAR, DEPARTMENT OF CHEMICAL PATHOLOGY

2. OUTLINE Introduction Overview of anatomical & Physiological changes in pregnancy Systemic biochemical changes Maternal and fetal health assessment Complications of pregnancy Conclusion References

3. INTRODUTION Normal human pregnancy lasts approximately 40 weeks from the last menstrual period. During pregnancy, a woman undergoes dramatic physiological and hormonal changes in biological composition that can be evaluated biochemically to monitor their wellbeing, and for detection of any anomaly.

4. BRIEF OVERVIEW OF PREGNANCY A fertilized ovum becomes an embryo after implantation in the uterus and development of a placenta; then becomes a fetus at 10 weeks after most primitive systemic structures have been formed. Pregnancy is divided into 3 trimesters of roughly 13 weeks each; and term pregnancy is adduced at 37 – 42 weeks of gestation.

5. ENDOMETRIAL CHANGES in ovarian CYCLE

6. Metabolic & biochemical changes in Pregnancy state Two compartment model is used in pregnancy: Mother & Fetus Mother: primary provider. Fetus: nutrient requiring organism; mainly glucose, amino acids, lactate, fatty acids, ketone bodies.

7. 10-20 % increase in BMR by the end of 3rd trimester Weight gain = 11 kgs, due to: Uterus Breast Increase blood volume Increased extravascular extracellular fluid Maternal reserves (increase in cellular water, fats & proteins).

8. The placenta The placenta and umbilical cord forms the primary link between mother and fetus …while keeping the maternal & fetal circulation separate, providing nourishment to fetus, eliminating fetal waste; and also produces hormones vital to pregnancy. Chorionic gonadotropin Placental lactogen Placental steroids The

9. The placenta is a highly active endocrine organ during gestation, secreting a variety of hormones with physiological effects. Efforts to study the action/function of these hormones in driving physiological changes during pregnancy has been attempted in two main ways. First, the expression and activity of the hormones have been manipulated in vivo by either exogenously administering or genetically manipulating the expression of hormones and hormone receptors to study the physiological activities.

10. Secondly, hormone analogs have been manipulated similarly in cultured cells and tissue explants to study the cellular and molecular mechanisms by which they modulate function. The effects of these hormones in non-pregnant study groups is required as controls, to provide information on the baseline and physiological changes that occur in the absence and presence of these placental-derived hormones respectively. These have not been very successful so far; and further studies have been limited by ethical considerations.

11. Normal Placental Transport Not transported Most proteins Thyroid hormones Maternal IgM, IgA Maternal/Fetal RBCs Actively transported Glucose Calcium Many amino acids Limited passive transport Unconjugated steroids Free fatty acids Passive transport Oxygen Carbon dioxide Sodium & Chloride Urea Ethanol Molecules up to 5000 Da having lipid solubility Receptor-mediated endocytosis Insulin Maternal IgG Low density lipoproteins

12. The amniotic fluid …a fluid-filled compartment, which the fetus lives throughout intrauterine life. It increases gradually during pregnancy, to about 1400 ml at term. Its volume per time can be a guide to fetal wellbeing: Oligohydramnios: low volume Polyhydramnios: high volume

13. Composition of amniotic fluid

14. Composition of amniotic fluid… contd

15. Maternal adaptation Placental hormones interplay to mediate maternal adaptations to pregnancy, parturition and lactation. Large quantities of estrogen, progesterone, placental lactogen and corticosteroids produced during pregnancy affects various metabolic, physiologic and endocrine systems. There is: An increase in resistance to angiotensin A predominance of lipid metabolism over glucose use Increased synthesis by the liver, of fibrinogen, thyroid – and steroid binding proteins.

16. General biochemical picture… Electrolytes show little change Urea nitrogen markedly Bicarbonate reduces as much as 20% almost throughout gestation. Creatine kinase markedly incr

17. Renal changes Pregnancy increases the GFR to about 170 ml/min/1.73m2 by 20 weeks and therefore increases the clearance of urea, creatinine and uric acid a decrease in the concentration of these analytes during pregnancy, until towards term when it normalizes. Glucosuria, up to 1000mg/d, due to incr GFR. …also, protein loss in urine can incr up to 300 mg/day.

18. Endocrine changes Progesterone prevent menses. 1,25 dihydroxyvitamin D is increased during pregnancy which promotes increased intestinal absorption of calcium and the transfer of calcium to the fetus. Estrogen stimulates an increase in plasma transport proteins: thyroxine binding globulin, (TBG), cortisol binding globulin (CBG) and sex hormone binding globulin (SHBG).

19. Estrogen also: Stimulates release of prolactin, up to 10 fold Suppress luteinizing and follicle stimulating hormone release The high concentration of TBG raises total T3 and T4, but causes a slight decrease in fT4.

20. Hepatic changes Albumin synthesis decreases Alkaline phosphatase (ALP) activity almost triples, due to ALP of placental origin. Hepatic clearance of cortisol decreases as estrogen stimulates hepatic production of CBG. The diurnal rhythm of cortisol is maintained.

21. Hematological changes Blood volume increases by up to 45% Plasma vol incr more rapidly than RBC mass Blood coagulation factors by up to 65% ESR, increasing the risk of thromboembolism.

22. Maternal and fetal health assessment Preconception evaluation should include: medical, reproductive and family history; physical examination and laboratory tests such as: Urinalysis, Hematocrit Blood group, rhesus factor & genotype Pap smear, HIV antibody Screening for TORCHES Gonococcus and chlamydia Hepatitis B surface antigen Depending on demographic risks: Genetic testing for cystic fibrosis, Thalassemias , IBEMs etc.

23. In suspected pregnancy, following a missed menses, some laboratory tests are conducted, which are useful for managing a normal or abnormal pregnancy: Pregnancy test – hCG of about 25 IU/L (urine), or 10 IU/L (serum). ... Other necessary obstetric maternal-fetal wellbeing monitoring routine: USS, fetal HR, lie & movement, uterine contractions etc.

24. Abnormal pregnancy biochemistry In event of certain risks in index pregnancy, screening for: Neural tube defects: anencephaly, meningomyelocele. Associated with folic acid deficiency. Elevated Alpha-fetoprotein (AFP) in maternal serum – screening. Down’s syndrome: Trisomy 21. Phenotype – moderate to severe mental retardation, hypotonia, congen . heart defect and flat facial profile. Triple test: serum hCG , AFP and unconjugated estriol, 15-18 weeks GA. Inhibin A (Quadruple test). Amniocentesis, karyotyping. Respiratory distress syndr : aka hyaline membr disease. About 10% of preterm births. Deficiency of pulmonary surfactant  collapse of alveoli during expiration (fetal atelectasis). Measurement of Lecithin: sphingomyelin ratio, phosphatidylcholine.

25. Gestational diabetes (GDM): defined as glucose intolerance of variable degree, first recognition during pregnancy. In pregnant mothers with metabolic syndrome; or previous pregnancy history of GDM, macrosomia (≥ 4000 g) or stillbirth OGTT, 24-28 weeks gestation. Also, certain complications may arise in pregnancies, such as: Ectopic pregnancy: serial quantitative hCG measurement with slow rate of increase. Normally, hCG should double every 2-3 days. Hyperemesis gravidarum: can cause dehydration, abnormal liver enzymes: 3-4x URL.

26. Preeclampsia: HTN, proteinuria, edema HELLP syndrome: RUQ pain, thrombocytopenia, DIC, very high LDH, ALT & AST, usually 5-10x URL Hemolytic disease of the newborn: when maternal antibodies reacts with antigen on fetal erythrocytes. Synonyms: Rhesus D isoimmunization, erythroblastosis fetalis. Can cause hydrops fetalis, hemolytic disease of the newborn, severe NNJ and kernicterus. Serial monitoring of amniotic fluid bilirubin, fetal exchange blood transfusion. Administration of anti- RhD immunoglobulin RhoGAM to sensitized mothers.

27. Liver disease of pregnancy: fatty liver of pregnancy: micro-vesicular fat in hepatocytes. Rapid onset of abdominal pain, malaise, nausea/vomiting, mild elevation of liver enzymes, bilirubin >6mg/dl, life-threatening hypoglycemia, hyperuricemia, renal failure. cholestasis of pregnancy: diffuse pruritus, pale stool, dark urine. Serum bilirubin >5mg/dl, ALP 2-4x URL. Elevated prothrombin time.

28. CONCLUSION Pregnancy is an awe-inspiring process of growth and development with diverse changes in physiology and biochemical features. Awareness of these changes and pregnancy-unique disorders is critical in the proper management of pregnancy.

29. references Tietz Textbook of Clinical Chemistry and Molecular Diagnostics; fifth Ed., by Burtis et al. Martin A. Crook; Clinical Chemistry and Metabolic Medicine, 8th Edition. Clinical Chemistry; Principles, Techniques & Correlations, 7th Ed., by Bishop et al. Oxford Handbook of Clinical Pathology; 17th Edition, Oxford University Press, London.

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