Physiological resetting in pregnancy

Fluid dilution and renal changes

 

• 8-10kg of maternal weight it due to fluid retention – increased extracellular fluid volume
• Larger increases have been seen in women taking regular exercise and smaller changes occur when there are complications such as pre-eclampsia and IUGR
• Plasma osmolality descreases by about 10mosmol/kg, under normal physiological circumstances this would result in rapid diuresis
• Interestingly there is also a decrease thirst threshold in pregnancy with women feeling the urge to drink at a lower plasma osmolality than if they were non-pregnant
• Oncotic pressure (colloid osmotic pressure) is also reduced – due to decrease albumin levels – this is likely to contribute to peripheral oedema. It is also one of the factors responsible for the marked increase that occurs in glomerular filtration
• The factors contributing to fluid retention are;
  • Sodium retention
  • Resetting of osmostat
  • Decrease in thirst threshold
  • Decrease in plasma oncotic pressure

 

• The consequences of fluid retention are;
  • Hb concentration falls
  • Haematocrit falls
  • Serum albumin concentration falls
  • Stroke vol increases
  • Renal blood flow increases

 

 

Blood

 

• Increased plasma volume causes haemoldilution of RBC
• The increase in erythropoeisis that pregnancy is associated with is outstripped by the increase in plasma vol
• Mean Hb conc falls from 13.3g/dL in the non-pregnant state to 10.9g/dL at 36 weeks
• Iron stores are most reliably measured using serum ferritin levels
• Folic acid supplementation is also important at preventing macrocytic anaemia. Renal clearance of folic acid increases during pregnancy resulting in a decrease in folate levels
• Increased numbers of WBC in particular PMN are found
• There is an increase in erythrocyte sedimentation rate probably due to increased fibrinogen concentrations

 

Cardiovascular System

 

• Early pregnancy is characterised by peripheral vasodilation
• Mean arterial pressure decreases by 10%
• Peripheral resistance decreased by 35%
• The results in initially an increase in heart rate and later an increase in stroke volume
• Progressive increase in heart rate occurs until the 3^rd trimester when levels are 10-15 beats/min greater and stoke vol increases by 10-20ml
• Altogether cardiac output increases from 5l/min to 7l/min at the 20^th week

 

Renal Function

 

• General vasodilation resulting in relaxation of smooth muscle also result in a dilated urinary tract
• By the 3^rd trimester most women have some degree of stasis of hydronephrosis
• This is one of the reasons that pregnant women are predisposed to ascending UTI’s
• Increased blood flow results in a 60-70% increase in renal blood flow with a resulting augmentation of the GFR by 50%
• Clearance of most substances in enhanced
• This results in reduced levels are urea and creatine during pregnancy
• There is also an increase in total protein excretion during pregnancy
• The increase in GFR is one of the factors contributing in glycosuria

 

 

Haematinic deficiency

 

• Major cause of anaemia is iron and folate deficiency

 

Consequences to the mother

• Depressed immunity
• Breathlessness
• Congestive heart failure may develop is levels fall below 3g/dl

 

Consequences to infant

• Fetal hypoxia resulting in placental hypertrophy and IUGR
• Folate deficiency can cause premature labour
• Low birth weight is associated with reduced immunity

 

• Signs of fetal anaemia (not normally seen unless Hb is <6g/dL
  • Polyhydramios
  • Enlarged fetal heart
  • Ascites and pericardial effusions
  • Hyperdynamic fetal circulation – measure by Doppler
  • Reduced fetal movements                                          
  • Abnormal CTG with reduced variability

 

 

Nutrition in Pregnancy

 

• On average women gain 12.5kg during pregnancy
• Overall requires an extra 400 kcal/day achieved by increased dietary intake and diminished energy expenditure. There is also a slight fall in maternal metabolism due to reduced levels of thyroid hormone

 

Metabolic adaptations

• Reduced gastric secretions and reduced gut motility
• Increased absorption of iron and calcium
• Increased urinary excretion of glucose, amino acids and several vitamins
• Concentration of most nutrients in the circulation is reduced, particularly water soluable nutrients
• On the other hand, lipids, fat soluable vitamins and certain specific carrier proteins are increased in concentration

 

Micronutrient Deficiencies

• Micronutrients is the collective term for both vitamins and minerals
• Micronutrient deficiencies often co-exist
• Iron deficiency can cause anaemia. May lead to low birth weight
• Folic acid – the large MRC randomised, controlled trial looked at the supplementation of folic acid (4mg/day) in the prevention of recurrent neural tube defects. It isn’t know whether supplementation will prevent the primary occurrence of neural tube defects. Requires folic acid to be taken prior to conception
• Zinc – evidence suggesting that zinc deficiency may be involved in complications such as pre-eclampsia, premature rupture of membranes and preterm delivery. Supplementation may benefit fetal immune system also
• Iodine deficiency can result in defective thyroid function in pregnancy and resulting cretinism. Supplemented by iodinised salt
• Magnesium deficiency may be associated with pre-eclampsia and preterm delivery
• Vitamin D deficiency may occur during pregnancy which can result in maternal osteomalacia and defective fetal calcium metabolism. Particularly common in Asian women who may have little exposure to sunlight and whose calcium absorption may be impaired by an excess of wholemeal cereals in the diet
• Generally mineral supplementation has only minor benefits and large supplementation may be detrimental to health e.g. Vit A

 

• Taller women have a better outcome in pregnancy than shorter women
• 450g/week weight gain is required for optimal outcome in terms of ore-eclampsia, intrauterine growth restriction and perinatal death
• Barker hypothesis, poor nutrition in utero makes individuals more susceptible to cardiovascular disease later on in life
• Pre-eclampsia is associated with an above average weight increase in pregnancy
• Women who have a low BMI are at increased risk of;
  • Preterm birth
  • IUGR
• However they have a decreased risk of ;
  • Pre-eclampsia
  • stillbrith

 

 

Maternal biochemical changes during pregnancy

 

• Total concentration of serum proteins decreases by about 1g/L during pregnancy
• Most of the decrease occurs during the first trimester
• Decrease in albumin and calcium mostly due to dilution effect – may be greater in pre-eclampsia when fluid retention can be greater than normal
• Increase in steroid binding proteins (by a factor of 6) results in an increase in total measurable steroid but a decrease in free steroid levels
• Alterations in clotting factors are due to the effects of oestrogen on the liver

 

Biochemical changes which occur during pregnancy;

 

• Some of these effects can be seen in women taking the oral contraceptive pill

 

Alkaline phosphatase

• Group of enzymes which hydrolyse organic phosphates at high pH
• Present in most tissues but at particularly high levels in the osteoblasts of the bone, placenta, intestinal epithelium and liver
• Levels of alkaline phosphatase nearly doubles during pregnancy, this is due to placental isoenzymes of this enzyme. Particularly rises during the final trimester of pregnancy
• Other causes of raised ALP;
  • In preterm infants, due to increases in the bone isoenzyme
  • In children due to prepubertal growth spurt
  • In elderly, the plasma bone isoenzymre activity may increase slightly
  • There is a gradual increase in the proportion of liver ALP with age

 

Human Chorionic Gonadotrophin

 

• Used to identify and follow both trophoblastic disease and normal pregnancy
• In normal pregnancy secreted by the placental trophoblasts, reaches a peak at 13 weeks of pregnancy
• In healthy pregnancy, levels rise to a range of 20,000 to 100,000 U/day and then decrease to 4,000 to 11,000 U/day later in pregnancy
• In normal pregnancy levels generally double every 48hours, in a failing pregnancy levels may not rise so quickly or get to the same level
• In the case of a hydatiform mole, levels of hCG rise to 300,000 U/day. After molar evacuation these levels drop so they are generally not detectable after 3 months. If trophoblastic tissue remains such as in a choriocarcinoma values will remain elevated