Physiological Changes In Pregnancy

Pregnancy is associated with normal physiological changes that assist fetal survival as well as preparation for labour. It is important to know what 'normal' parameters of change are in order to diagnose and manage common medical problems of pregnancy, such as hypertension, gestational diabetes, anaemia and hyperthyroidism.

Pituitary

• FSH/LH fall to low levels.
• ACTH and melanocyte-stimulating hormone increase.
• Prolactin increases.

Thyroid and parathyroid^1,2

• Thyroxine-binding globulin (TBG) concentrations rise due to increased oestrogen levels.
• T4 and T3 increase over first half of pregnancy but there is a normal to slightly decreased amount of free hormone due to increased TBG-binding.
• TSH production is stimulated, although in healthy individuals this is not usually significant. A large rise in TSH is likely to indicate iodine deficiency or subclinical hypothyroidism.
• Serum calcium levels decrease in pregnancy which stimulates an increase in parathyroid hormone (PTH).
• Colecalciferol (vitamin D3) is converted to its active metabolite, 1,25-dihydroxycolecalciferol, by placental 1α-hydroxylase.

Adrenal and pancreas³

• Cortisol levels increase in pregnancy, which favours lipogenesis and fat storage.
• Insulin response also increases so blood sugar should remain normal or low.
• Peripheral insulin resistance may also develop over the course of pregnancy and gestational diabetes is thought to reflect a pronounced insulin resistance of this sort.

• Progesterone reduces systemic vascular resistance by about 20% early in pregnancy. Postural hypotension may result.
• Diastolic and systolic blood pressure tend to fall during mid pregnancy and then return to normal by week 36.
• Venous return in the inferior vena cava can be compromised in late pregnancy if a woman lies flat on her back. This is relieved by lying in the left lateral position.
• Increased circulating angiotensin II encourages water and sodium retention leading to an increased plasma volume (to 50% by 30 weeks) and predisposing to oedema. This enables increased uterine blood flow to meet growing nutritional and oxygenation needs of the fetus. It also enables blood loss (average 500 ml) at delivery to be met without physiological decompensation.
• Advise women not to take up unaccustomed, vigorous exercise in pregnancy as there is a risk of diversion of uterine blood flow to the skeletal muscles.
• Blood flow to kidneys, skin and mucosa increases.
• Cardiac output increases by 30-50% with 15% increase in heart rate and 25-30% increased stroke volume. Much of this adjustment occurs prior to 12 weeks' gestation and so impaired cardiac function is likely to present problematically in early pregnancy or with the sudden increase in pre-load in the third stage of labour.

• Tidal volume increases by about 200 ml, increasing vital capacity and decreasing residual volume. In later stages of pregnancy, splinting of the diaphragm may occur with some decrease in tidal volume. Respiratory rate does not alter significantly.
• Increased oxygen consumption by approximately 20%.
• State of compensated respiratory alkalosis - arterial PCO₂ drops, arterial PO₂ remains unchanged and decrease in bicarbonate prevents pH change. Lower maternal PCO₂ facilitates oxygen/carbon-dioxide transfer to/from fetus.
• Many women complain of feeling short of breath in pregnancy without explanatory pathology. The mechanism of this is not fully understood

• Appetite is usually increased, sometimes with specific cravings.
• Progesterone causes relaxation of the lower oesophageal sphincter and increased reflux, making many women prone to heartburn.
• GI motility is reduced and transit time is consequently longer. This allows increased nutrient absorption. Constipation is common.
• The gallbladder may dilate and empty less completely. Pregnancy also predisposes to the precipitation of cholesterol gallstones.
• Gums become spongy, friable and prone to bleeding. Good dental care is important.

• Glomerular filtration rate (GFR) increases by 50% early in pregnancy, increasing creatinine clearance. Serum creatinine and urea will fall by about 25%.
• Increased GFR also increases filtered sodium. Aldosterone levels rise by 2-3 times to reabsorb the filtered sodium.
• Increased GFR and impaired tubular reabsorption of glucose produce glucosuria in approximately 15% of normal pregnancies.
• Proteinuria is abnormal in pregnancy.
• The smooth muscle of the renal pelvis and ureter become relaxed and dilated, kidneys increase in length and ureters become longer, more curved and with an increase in residual urine volume. Bladder smooth muscle also relaxes, increasing capacity and risk of UTI. Approximately 5% of pregnant women have bacteriuria, often asymptomatic, and there is a greater risk of developing pyelonephritis in pregnancy.

• Dilutional anaemia is caused by the rise in plasma volume. Elevated erythropoietin levels increase the total red cell mass by the end of the second trimester but haemoglobin concentrations never reach pre-pregnancy levels.
• A modest leukocytosis is observed.
• A normal pregnancy creates a demand for about 1000 mg of additional iron. This equates to 60 mg elemental iron or 300 mg ferrous sulphate per day.
• Serum iron falls during pregnancy whilst transferrin and total iron binding capacity rise.
• Levels of some clotting factors (VII, VIII, IX and X) and fibrinogen increase whilst fibrinolytic activity decreases. These changes protect from haemorrhage at delivery but also make pregnancy a hypercoagulable state with increased risk of thromboembolism.
• Protein C and Protein S activities gradually reduce during pregnancy. Interpretation of thrombophilia screens is difficult during pregnancy and testing following a thromboembolic event should wait until after the puerperium.⁷
• Serum alkaline phosphatase increases during pregnancy - due to placental production.
• Serum albumin decreases.

• Changes in energy requirements in pregnancy remain controversial - healthy levels of fat deposition and variation in women's physical activity levels cause uncertainty as to the recommendations we should make for this time.⁸
• The basal metabolic rate increases slowly over the course of pregnancy, by 15-20%.
• In women with normal BMIs, energy requirement does not increase significantly during the first trimester, increases by about 350 Kcal/day in the second trimester and 500 Kcal/day in the third.⁸
• Active energy expenditure tends to fall over pregnancy.
• Normal weight gain is approximately 12.5 kg (usually at a rate of 0.5 kg per week for the last 20 weeks). 5 kg is the fetus, placenta, membranes and amniotic fluid and the rest is maternal stores of fat and protein and increased intra- and extra-vascular volume.

• Hyperpigmentation of the umbilicus, nipples, abdominal midline (linea nigra) and face (chloasma) are common due to the hormonal changes of pregnancy.
• Hyperdynamic circulation and high levels of oestrogen may cause spider naevi and palmar erythema.
• Striae gravidarum ("stretch marks") are common.

• Increased ligamental laxity caused by increased levels of relaxin contribute to back pain and pubic symphysis dysfunction.
• Shift in posture with exaggerated lumbar lordosis leading to the typical gait of late pregnancy.⁹