Pregnancy

Published on 02/03/2015 by admin

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Pregnancy

Maternal physiology

Maternal physiology changes so dramatically during pregnancy that reference intervals for biochemical tests in non-pregnant women are often not applicable. The main differences in commonly requested tests are shown in Table 76.1. These differences should not be misinterpreted as indicating that some pathology is present.

Table 76.1

Reference intervals in the third trimester of pregnancy, and how they compare with non-pregnant controls

Serum/blood measurement	Pregnant	Non-pregnant
Potassium (mmol/L)	3.2–4.6	3.5–5.3
Chloride (mmol/L)	97–107	95–108
Bicarbonate (mmol/L)	18–28	22–29
Urea (mmol/L)	1.0–3.8	2.5–7.8
Glucose (fasting) (mmol/L)	3.0–5.0	4.0–5.5
Adjusted Calcium (mmol/L)	2.2–2.8	2.2–2.6
Magnesium (mmol/L)	0.6–0.8	0.7–1.0
Albumin (g/L)	32–42	35–50
Bilirubin (µmol/L)	<15	<21
Alanine aminotransferase (U/L)	3–28	3–55
Aspartate aminotransferase (U/L)	3–31	12–48
Alkaline phosphatase (U/L)	174–400	30–130
Blood H⁺ (nmol/L)	34–50	35–45
Blood PCO₂ (kPa)	3.0–5.0	4.4–5.6

Weight gain

The mean weight gain in pregnancy is 12.5 kg, but there is a very large standard deviation (about 4 kg). The gain in weight is made up of several components:

The products of conception. These include the fetus, placenta and amniotic fluid.

Maternal fat stores. These may account for up to 25% of the weight increase.

Maternal water retention. Total body water increases by about 5 L, mostly in ECF. The volume of the intravascular compartment increases by more than 1 L.

Respiratory function

Mild hyperventilation occurs from early pregnancy, probably due to a centrally mediated effect of progesterone, and PCO₂ falls. However, blood hydrogen ion concentration is maintained within non-pregnant limits, since the plasma bicarbonate falls due to an increased renal excretion of bicarbonate. Oxygen consumption increases by about 20%, but PO₂ is relatively unchanged.

Renal function

Because of increases in plasma volume and cardiac output, renal blood flow increases. The GFR rises early in pregnancy, and creatinine clearance may be 150 mL/minute or more by 30 weeks. Serum urea and creatinine concentrations fall. Tubular function alters and, in particular, there is a reduction in the renal threshold for glucose. Intermittent glycosuria may be present in up to 70% of pregnancies. Tubular reabsorption of uric acid and amino acids alters, and their excretion in urine increases.

Carbohydrate metabolism

The fasting blood glucose falls early in pregnancy, probably because of substrate utilization. The response to a standard carbohydrate challenge is altered in late pregnancy.

Protein metabolism

Serum albumin concentration falls gradually from early pregnancy and this is related to ECF expansion. The concentrations of many other proteins increase, particularly placental proteins such as alkaline phosphatase of placental origin, transport proteins such as transferrin, and hormone-binding glycoproteins such as thyroxine-binding globulin, and fibrinogen.

Hormonal changes

Oestrogens and progesterone are secreted in greater amounts early in pregnancy, and hormones such as HCG and HPL are produced by the placenta. These hormonal changes form the biochemical basis of the diagnosis of pregnancy. For example, HCG should be undetectable in the non-pregnant state.

Pregnancy-associated pathology

Morbidity during pregnancy may be due to pre-existing medical conditions in the mother such as diabetes mellitus, hypertension, renal disease, thyrotoxicosis, or due to pregnancy-associated conditions.

Gestational diabetes

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. This definition applies irrespective of treatment modality used and whether or not the condition persists after pregnancy. It recognizes the possibility that unrecognized glucose intolerance may have antedated or begun concomitantly with the pregnancy. Depending on the population studies, the prevalence of GDM may be as high as 10% of all pregnancies. Maternal glycaemic status should be rechecked 6 weeks after delivery; women with GDM are at increased risk of developing diabetes, usually type 2, after pregnancy. Maternal hyperglycaemia promotes hyperinsulinism in the fetus (Fig 76.1). Insulin in a growth factor, and babies of poorly controlled diabetic patients are large and bloated. GDM is associated with increased fetal morbidity and mortality. Tight control of diabetes during pregnancy decreases complications.

Fig 76.1 Diabetes mellitus in pregnancy is associated with fetal hyperinsulinaemia. In utero this leads to increased growth, while post-natally the persisting hyperinsulinaemia causes neonatal hypoglycaemia.

Hypertension

The patient who develops hypertension in pregnancy – a condition described variously as pre-eclampsia or pregnancy-induced hypertension – is at increased risk of placental insufficiency and consequent fetal intrauterine growth retardation. The hypertension is thought to be the causative factor of eclampsia, a severe illness that usually occurs in the second half of pregnancy and is characterized by generalized convulsions, extreme hypertension and impaired renal function including proteinuria. This disease is a significant cause of maternal death, which occurs most commonly as a result of cerebral haemorrhage. The features of pre-eclampsia are shown in Figure 76.2. There are similarities between pre-eclampsia and two other conditions seen in pregnancy – namely the HELLP syndrome (haemolysis, elevated liver enzymes and low platelets) and acute fatty liver of pregnancy. Blood-borne factors from a poorly perfused placenta may activate the maternal endothelium, causing endothelial dysfunction and vascular damage. Altered liver metabolism may also contribute, especially to acute fatty liver of pregnancy, by contributing to triglyceride accumulation in the liver. Frequently it is difficult to decide on the optimum time for delivery. Laboratory investigations may help inform this decision. These include transaminases (AST and ALT), LDH, platelet count, triglyceride and urine protein.

Fig 76.2 Clinical features of pre-eclampsia.

Obstetric cholestasis

This is a multifactorial condition of pregnancy characterized by pruritis in the absence of a skin rash, with abnormal liver function tests, neither of which has an alternative cause and both of which resolve after birth. It is likely that the high levels of circulating hormones impair normal bile flow in the gall bladder. It is more common in the third trimester, but usually subsides within a few days of delivery. Along with maternal morbidity it is also associated with fetal risks – preterm birth and intrauterine death. Known risk factors include personal or family history of cholestasis, multiple pregnancy, gallstones and hepatitis C. Although elevated serum bile acid concentration is considered a sensitive indicator of obstetric cholestasis, normal levels do not exclude the diagnosis. Other features include pale stools, dark urine, jaundice and elevated liver enzymes. Treatment is directed towards symptomatic relief and includes topical antihistamines and oral urdodeoxycholic acid; supplemental vitamin K is also prescribed. In severe cases early elective delivery may be considered.

Drugs in pregnancy

Many women have, of necessity, to continue to take drugs during pregnancy. No drugs are without risk to the developing fetus, and drug levels should be kept as low as possible during gestation and thereafter if the mother is breast feeding, since many drugs are secreted in breast milk. Of particular concern are anticonvulsant drugs. Careful monitoring of levels is necessary to steer between the dangers of maternal seizures and potential fetal damage from the drug.

Case history 62

A 20-year-old woman in her first pregnancy was referred to hospital by her GP when she was 31 weeks pregnant. At 12 weeks pregnant she appeared well, had no oedema and her blood pressure was 110/70 mmHg. Now, she complained that she was unable to remove her wedding ring and that her vision was blurred. On examination ankle oedema was also observed and her blood pressure was found to be 180/110 mmHg.

• What is the most likely diagnosis?

• What sideroom test(s) should be performed?

• What biochemical investigations should be performed immediately?

Comment on page 170.

Clinical note

Pregnancy is the commonest cause of amenorrhoea in a woman of reproductive age. A pregnancy test should always be performed before other endocrine investigations of the cause of absent menstrual bleeding.

Pregnancy

Physiological changes occur in pregnancy, altering many biochemical reference intervals. Do not be misled into believing that they indicate pathology.

Diabetes in pregnancy is associated with increased fetal mortality and morbidity. Good diabetic control during pregnancy decreases complications. The baby of a diabetic mother has an increased probability of developing respiratory distress syndrome.

Hypertension and a rising serum urate concentration are early features in the development of pre-eclampsia, a rapidly progressing condition that carries considerable risk to mother and fetus.

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