Tetralogy of Fallot / TOF is a cardiac anomaly that refers to a combination of four related heart defects that commonly occur

together. The four defects are: Pulmonary stenosis narrowing of the pulmonary valve and outflow tract or area below the valve that creates an obstruction (blockage) of blood flow from the right ventricle to the pulmonary artery Ventricular septal defect / VSD Overriding aorta the aortic valve is enlarged and appears to arise from both the left and right ventricles instead of the left ventricle as in normal hearts Right ventricular hypertrophy thickening of the muscular walls of the right ventricle, which occurs because the right ventricle is pumping at high pressure

blood ("blue") returning to the right atrium and right ventricle to be pumped out the aorta to the body. This "shunting" of oxygen-poor blood from the right ventricle to the body results in a reduction in the arterial oxygen saturation so that babies appear cyanotic, or blue. The cyanosis occurs because oxygen-poor blood is darker and has a blue color, so that the lips and skin appear blue. The extent of cyanosis is dependent on the amount of narrowing of the pulmonary valve and right ventricular outflow tract. A narrower outflow tract from the right ventricle is more restrictive to blood flow to the lungs, which in turn lowers the arterial oxygen level since more oxygen-poor blood is shunted from the right ventricle to the aorta. HIDE ALL Signs and Symptoms of Tetralogy of Fallot HIDE Tetralogy of Fallot is most often diagnosed in the first few weeks of life due to either a loud murmur or cyanosis. Babies with tetralogy of Fallot usually have apatent ductus arteriosus at birth that provides additional blood flow to the lungs, so severe cyanosis is rare early after birth. As the ductus arteriosus closes, which it typically will in the first days of life, cyanosis can develop or become more severe. The degree of cyanosis is proportional to lung blood flow and thus depends upon the degree of narrowing of the outflow tract to the pulmonary arteries. Rapid breathing in response to low oxygen levels and reduced pulmonary blood flow can occur. The heart murmur, which is commonly loud and harsh, is often absent in the first few days of life. The arterial oxygen saturation of babies with tetralogy of Fallot can suddenly drop markedly. This phenomenon, called a "tetralogy spell," usually results from a sudden increased constriction of the outflow tract to the lungs so that pulmonary blood flow is further restricted. The

lips and skin of babies who have a sudden decrease in arterial oxygen level will appear acutely more blue. Children having a tetralogy spell will initially become extremely irritable in response to the critically low oxygen levels, and they may become sleepy or unresponsive if the severe cyanosis persists. A tetralogy spell can sometimes be treated by comforting the infant and flexing the knees forward and upward. Most often, however, immediate medical attention is necessary. Diagnosis of Tetralogy of Fallot HIDE When a newborn with significant cyanosis is first seen, he or she is often placed in supplemental oxygen. The increased oxygen improves the child's oxygen levels in cases of lung disease, but breathing extra oxygen will have little effect on the oxygen levels of a child with tetralogy of Fallot. Failure to respond to this "hyperoxia test" is often the first clue to suspect a cyanotic cardiac defect. Infants with tetralogy of Fallot can have normal oxygen levels if the pulmonary stenosis is mild (referred to as "pink" tetralogy of Fallot). In these children, the first clue to suggest a cardiac defect is detection of a loud murmur when the infant is examined. Once congenital heart disease is suspected, echocardiography can rapidly and accurately demonstrate the four related defects characteristic of tetralogy of Fallot. Cardiac catheterization is occasionally required to evaluate the size and distribution of the pulmonary arteries and to clarify the branching patterns of the coronary arteries. Catheterization can also demonstrate whether patients have pulmonary blood flow supplied by an abnormal blood vessel from the aorta (aortopulmonary collateral). Treatment for Tetralogy of Fallot HIDE

A small percentage of children with tetralogy of Fallot may also have additional ventricular septal defects, an atrial septal defect / ASD or abnormalities in the branching pattern of their coronary arteries. Some patients with tetralogy of Fallot have complete obstruction to flow from the right ventricle, or pulmonary atresia. Tetralogy of Fallot may be associated with chromosomal abnormalities, such as 22q11 deletion syndrome. The pulmonary stenosis and right ventricular outflow tract obstruction seen with tetralogy of Fallot usually limits blood flow to the lungs. When blood flow to the lungs is restricted, the combination of the ventricular septal defect and overriding aorta allows oxygen-poor

Once tetralogy of Fallot is diagnosed, the immediate management focuses on determining whether the child's oxygen levels are in a safe range. If oxygen levels are critically low soon after birth, a prostaglandin infusion is usually initiated to keep the ductus arteriosus open which will provide additional pulmonary blood flow and increase the child's oxygen level. These infants will usually require surgical intervention in the neonatal period. Infants with normal oxygen levels or only mild cyanosis are usually able to go home in the first week of life. Complete repair is usually done electively when the children are about six months of age, as long as the oxygen levels remain adequate. Progressive or sudden decreases in oxygen saturation may prompt earlier corrective repair. Surgical correction of the defect is always necessary. Occasionally, patients will require a surgical palliative procedure prior to the final correction. Corrective repair of tetralogy of Fallot involves closure of the ventricular septal defect with a synthetic Dacron patch so that the blood can flow normally from the left ventricle to the aorta. The narrowing of the pulmonary valve and right ventricular outflow tract is then augmented (enlarged) by a combination of cutting away (resecting) obstructive muscle tissue in the right ventricle and by enlarging the outflow pathway with a patch. In some babies, however, the coronary arteries will branch across the right ventricular outflow tract where the patch would normally be placed. In these babies an incision in this area to place the patch would damage the coronary artery so this cannot safely be done. When this occurs, a hole is made in the front surface of the right ventricle (avoiding the coronary artery) and a conduit (tube) is sewn from the right ventricle to the bifurcation of the pulmonary arteries to provide

unobstructed blood flow from the right ventricle to the lungs. Treatment for Tetralogy of Fallot: Results HIDE Survival of children with tetralogy of Fallot has improved dramatically over recent decades. In the absence of confounding risk factors, more than 95 percent of infants with tetralogy of Fallot successfully undergo surgery in the first year of life. Surgical repair is more difficult when the pulmonary arteries are critically small or when the lung blood flow is supplied predominantly by aortopulmonary collaterals. Most babies are fairly sick in the first few days after surgery, since the right ventricle is "stiff" from the previous hypertrophy (thickness) and because an incision is made into the muscle of the ventricle, making the muscle temporarily weaker. This right ventricular dysfunction usually improves significantly in the days following surgery. Patients may also have rhythm problems after surgery. An abnormally fast rhythm (called junctional tachycardia) may occur and may require treatment with medication or the use of a temporary pacemaker. This abnormal rhythm is usually temporary and the rhythm generally will return to normal as the right ventricle recovers. Patients are also at risk for slow heart rates after surgery due to heart block. Heart block may be caused by injury to or inflammation of the conduction system in the heart. In many patients, the conduction improves and normal rhythm returns. Rarely, a permanent pacemaker may be necessary. Since a normal circulation is produced by the tetralogy of Fallot repair procedure, long-term cardiac function is usually excellent. However, the repair does usually leave the child with a leaky (insufficient) pulmonary valve. In this situation, after the right ventricle pumps blood out to the pulmonary arteries, some of the blood will flow back into

the right ventricle. This creates extra volume in the right ventricle forcing it to work harder and become dilated. In a small percentage of children, this pulmonary insufficiency can lead to diminished function of the right ventricle. Symptoms of fatigue, especially with exercise, may develop. In these cases, replacement of the pulmonary valve is often recommended. Patients who have had repair of tetralogy of Fallot can also redevelop a narrowing at the outflow area or in the branch (left or right) pulmonary arteries, which will cause the right ventricle to pump at abnormally high pressures. If these problems occur, surgical intervention to further widen the outflow tract or pulmonary arteries may be necessary. Narrowing the pulmonary arteries can sometimes be treated without surgery, with balloon dilation of the vessels during cardiac catheterization. Long-term follow-up with a cardiologist to detect recurrent or new problems as early as possible is essential. Follow-up visits in the cardiology clinic usually consist of a physical examination, electrocardiogram and periodic echocardiography. In addition, these visits will also include occasional cardiac MRI scans, exercise stress tests and Holter evaluations as a child reaches the teenage and adult years.

Coarctation of the aorta Aortic coarctation is a narrowing of part of the aorta (the major artery leading out of the heart). It is a type of birth defect. Coarctation means narrowing. Causes The aorta carries blood from the heart to the vessels that supply the body with blood and nutrients. If part of the aorta is narrowed, it is hard for blood to pass through the artery. Aortic coarctation is more common in persons with certain genetic disorders, such as Turner syndrome.

Aortic coarctation is one of the more common heart conditions that are present at birth (congenital heart conditions). It is usually diagnosed in children or adults under age 40. This condition may be related to cerebral aneurysms, which can increase the risk for stroke. Coarctation of the aorta may be seen with other congenital heart defects, such as: Bicuspid aortic valve Defects in which only one ventricle is present Ventricular septal defect Symptoms Symptoms depend on how much blood can flow through the artery. Other heart defects may also play a role. Around half of newborns with this problem will have symptoms in the first few days of life. In milder cases, symptoms may not develop until the child has reached adolescence. Symptoms include: Chest pain Cold feet or legs Dizziness or fainting Decreased ability to exercise Failure to thrive Leg cramps with exercise Nosebleed Poor growth Pounding headache Shortness of breath Note: There may be no symptoms. Exams and Tests

The health care provider will perform a physical exam and take the blood pressure and pulse in the arms and legs. The pulse in the groin (femoral) area or feet will be weaker than the pulse in the arms or neck (carotid). Sometimes, the femoral pulse may not be felt at all. The blood pressure in the legs is usually weaker than in the arms. Blood pressure is usually higher in the arms after infancy. The doctor will use a stethoscope to listen to the heart and check for murmurs. People with aortic coarctation have a harsh-sounding murmur that can be heard from the back. Other types of murmurs may also be present. Coarctation is often discovered during a newborn's first examination or well-baby exam. Taking the pulse in an infant is an important part of the examination, because there may not be any other symptoms until the child is older. Tests to diagnose this condition may include: Cardiac catheterization and aortography Chest x-ray Echocardiography is the most common test to diagnose this condition, and it may also be used to monitor the patient after surgery Heart CT may be needed in older children MRI or MR angiography of the chest may be needed in older children Both Doppler ultrasound and cardiac catheterization can be used to see if there are any differences in blood pressure in different areas of the aorta. Treatment Most newborns with symptoms will have surgery either right after birth or soon afterward. First they will receive medications to stabilize them.

Children who are diagnosed when they are older will also need surgery. Usually, the symptoms are not as severe, and more time will be taken to plan for surgery. During surgery, the narrowed part of the aorta will be removed or opened. If the problem area is small, the two free ends of the aorta may be re-connected. This is called an end-to-end anastomosis. If a large part of the aorta is removed, a Dacron graft (a man-made material) or one of the patient's own arteries may be used to fill the gap. A tube graft connecting two parts of the aorta may also be used. Sometimes, doctors will try to stretch open the narrowed part of the aorta by using a balloon that is widened inside the blood vessel. This type of procedure is called a balloon angioplasty. It may be done instead of surgery, but it has a higher rate of failure. Older children usually need medicines to treat high blood pressure after surgery. Some will need lifelong treatment for this problem. Outlook (Prognosis) Coarctation of the aorta can be cured with surgery. Symptoms quickly get better after surgery. However, there is an increased risk for death due to heart problems among those who have had their aorta repaired. Without treatment, most people die before age 40. For this reason, doctors usually recommend that the patient has surgery before age 10. Most of the time, surgery to fix the coarctation is done during infancy. Narrowing or coarctation of the artery can return after surgery. This is more likely in persons who had surgery as a newborn. Possible Complications Complications that may occur before, during, or soon after surgery include: Aortic aneurysm Aortic dissection

Aortic rupture Bleeding in the brain Early development of coronary artery disease (CAD) Endocarditis (infection in the heart) Heart failure Hoarseness Kidney problems Paralysis of the lower half of the body (a rare complication of surgery to repair coarctation) Severe high blood pressure Stroke Long-term complications include: Continued or repeated narrowing of the aorta Endocarditis High blood pressure When to Contact a Medical Professional Call your health care provider if: You or your child has symptoms of coarctation of the aorta You develop fainting or chest pain (these may be signs of a serious problem) Prevention There is no known way to prevent this disorder. However, being aware of your risk may lead to early diagnosis and treatment. Alternative Names Aortic coarctation

I. Cardiac Invasive Monitoring: Cardiac output is increased in pregnancy but is essentially unchanged over the course of pregnancy. Heart rate gradually rises 5 to 10 beats per minute over the course of pregnancy. Cardiac output (CO) is the product of stroke volume (SV) and heart rate (HR) (CO = SV X HR), both of which increase during pregnancy and contribute to the overall rise in CO. Value (36-38 weeks) 6.2 1.0

calculated using Ohm's law: TPR = MAP X 80/CO; where TPR is total peripheral resistance (dyne.sec.cm-5), MAP is mean arterial pressure (millimeters of mercury [mm Hg]), and CO is cardiac output (L/min). 10-18 weeks 7.26 1.56 18-26 weeks 7.60 1.63 26-34 weeks 7.38 1.63 34-42 weeks 6.37 1.48 70 14 1,118 325

Measure Cardiac output (L/min)

Measure Cardiac output (CO) Systemic vascular resistance (SVR) Heart rate Pulmonary vascular resistance Colloid oncotic pressure Mean arterial pressure (MAP) Pulmonary capillary wedge pressure (PCWP) Central venous pressure (CVP) Left ventricular stroke work index

Units liters/minute dyne cm second-5 beats/minute dyne cm second-5 mm Hg

Stroke volume (mL) 85 21 85 21 82 21 SVR (dyne cm second) Heart rate (beats/min) Mean arterial pressure (mm Hg) 966 226 901 224 932 240

1,210 266 83 10

87 14 90 14 92 14

92 7

78 22 18.0 1.5

87 7

84 7

84 7

86 7

III. Third-Trimester Arterial Blood Gas Values: Increasing progesterone levels drive a state of chronic hyperventilation, as reflected by a 30 to 50% increase in tidal volume by 8 weeks' gestation. Chronic mild hyperventilation results in increased alveolar oxygen (PAo2) and decreased arterial carbon dioxide (Paco2) from normal levels of 37 to 40 mm Hg to 27 to 32 mm Hg. The drop in Paco2 is especially critical, because it drives a more favorable carbon dioxide (CO2) gradient between the fetus and mother, facilitating CO2 transfer. The low maternal Paco2 results in a chronic respiratory alkalosis. The base values in normal pregnancy at normal and moderate altitude: Normal Altitude 7.44 0.04 85 5 Moderate Altitude (1,388 M, PROVO, UT) 7.46 0.02 86.2 7.3 96 1 29.7 2.8 26.6 2.7

90.3 5.8

mm Hg

7.5 1.8

mm Hg

3.6 2.5

mm Hg

48 6

g mm

II. Cardiac Non-invasive Monitoring: Maternal hemodynamics refers to the relationships between blood pressure, cardiac output, and vascular resistance. Blood pressure is measured by auscultation, use of an automated cuff, or directly with an intraarterial catheter. Cardiac output (CO) is measured by dilutional techniques requiring central venous access, by Doppler or two-dimensional echocardiographic techniques, or by electrical impedance. Peripheral resistance is Measure Arterial pH Arterial Po2 O2 Saturation (%) Arterial Pco2 (mm

Normal Values in Pregnancy

Hg) Sodium bicarbonate (mEq/L) 22.0 2.1

18.6 1.9

First Trimester Second Trimester Third Trimester Inspiratory Capacity: First Trimester Second Trimester Third Trimester Expiratory Reserve Volume: First Trimester Second Trimester Third Trimester Residual Volume: First Trimester Second Trimester Third Trimester

3.8 3.9 4.1

Liters Liters Liters

(ALT, IU/L) Total bilirubin (IU/L)

30) 4 (2-10) 4 (2-9) 4 (2-10)

VI. Electrolytes, Osmolality, and Renal Function: 2.6 2.7 2.9 Liters Liters Liters The increase in total body water of 6.5 to 8.5L by the end of gestation represents one of the most significant adaptations of pregnancy. The water content of the fetus, placenta, and amniotic fluid at term accounts for about 3.5L. Additional water is accounted for by expansion of volume by 1,200 to 1,300 ml, and red blood cells by 300 to 400 ml. The remainder is attributed to extravascular fluid, intracellular fluid in the uterus and breasts, and expanded adipose tissue. Expansion in plasma volume begins shortly after conception, partially mediated by a change in maternal osmoregulation through altered secretion of arginine vasopressin (AVP) by the posterior pituitary. Water retention exceeds sodium retention; although an additional 900 mEq of sodium decrease by 3 to 4 mmol/L. Renal plasma flow (RPF) increases markedly from early in gestation and may actually initially begin to increase during luteal phase before implantation. RPF rises 75% over non-pregnant levels by 16 weeks' gestation. The increase is maintained until 34 weeks' gestation, when a decline in RPF of 25% occurs. Like RPF, glomerular filtration rate (GFR) as measured by inulin clearance increases by 5 to 7 weeks. By the end of the first trimester, GFR is 50% higher than in non-pregnant state, and this is maintained until the end of the pregnancy. The creatinine clearance in pregnancy is greatly increased to values of 150 to 200 ml/min (normal: 120 ml/min). As with GFR, the increase in creatinine clearance occurs by 5 to 7 weeks' gestation, and normally is maintained until the third trimester. 12 20 28 38 Weeks Weeks Weeks Weeks 267279 269285 273283

IV. Pulmonary Function Tests: Increased tidal volume results in an overall parallel rise in minute ventilation, despite a stable respiratory rate. (Minute ventilation = Tidal volume X Respiratory rate). During pregnancy, the mucosa of the nasopharynx becomes hyperemic and edematous with hypersecretion of mucous due to increased estrogen. These changes often lead to marked nasal stuffiness; epistaxis is also common. Placement of nasogastric tubes may cause excessive bleeding if adequate lubrication is not used. Polyposis of the nose and nasal sinuses develops in some individuals but regresses in postpartum period. Because of these changes, many gravid women complain of chronic cold symptoms. However, the temptation to use nasal decongestants should be avoided because of risk of hypertension and rebound congestion. 8-11 Weeks 20-23 Weeks 16 (1518) 650 (625725) 28-31 Weeks 18 (1520) 650 (575720) 36-40 Weeks 17 (1618) 700 (660755)

1.2 1.2 1.2

Liters Liters Liters

1.2 1.1 1.0

Liters Liters Liters

V. Liver Function Tests: The size and histology of the liver are unchanged in pregnancy. However, many clinical and laboratory signs usually associated with liver disease are present. Spider angiomas and palmar erythema, caused by elevated estrogen levels, are normal and disappear, soon after delivery. The serum albumin and total protein levels fall progressively during gestation. By term, albumin levels are 25% lower than non-pregnant levels. Despite an overall increase in total body protein, decreases in total protein and albumin concentrations occur as a result of hemodilution. Week 12 Week 32 Intrapartum

Measure

Respiratory Rate 15 (14(br/min) 20) 640 (550710)

Tidal Volume (mL)

Peak Flows (5th% Shown as Lower Limit of Normal) Stable Over Gestation: Measure Peak Flow (L/Min) Standing Sitting Supine >320 >310 >300 Mean Values: Vital Capacity:

Measure

Total alkaline phosphatase 42 (17- 82 (46(IU/L) 88) 165) 97 (48-249) Gamma glutamyl transferase (IU/L)

Measure Total osmolality (mosmol/kg) Sodium (mmol/L) Potassium (mmol/L)

7 (2-18) 6 (3-20)

9 (5-79)

271-289

Aspartate transaminases (AST, IU/L) 9 (4-18) 9 (5-21) Alanine transaminases 9 (4-

11 (5-103)

133-141 136-142 135-143 135-141 3.5-4.3 3.5-4.3 3.5-4.4 3.6-4.5

8 (2-22) 12 (5-115)

Chloride (mmol/L)

102-108 103-111 104-112 102-111

0.10 0.58 Creatinine (mg/dL) 0.03 Total cholesterol (mg/dL) 153.5 3.8 70.1 4.5 0.42 0.03

0.13 0.50 0.04 194.0 5.2 109.6 5.8 0.34 0.02

0.11 0.50 0.03 218.3 6.4 139.6 6.9 0.21 0.02

0.13 0.57 0.03 220.4 8.4 159.0 8.1 0.67 0.04

Hemoglobin (g/dL) First trimester >11.1 Second trimester >10.64 Third trimester >10.47 Term >11.5 Hematocrit (%) First trimester Second trimester Third trimester Term

MCH, pg First trimester Second trimester Third trimester Term MCHC, g/dL First trimester Second trimester Third trimester Term >30.1 >29.9 >30.2 >30.1

Creatinine clearance (ml/24 hours) 76-188 88-168 40-192 52-208 Blood urea nitrogen (BUN) Serum albumin (g/L) Urine volume (mL/24 hours

1.7-4.4 1.9-5.3 1.9-4.2 1.8-4.6 37-47 7502,500 34-42 8502,400 31-42 7502,700 31-39 5503,900

Triglycerides Free fatty acids (mEq/L)

>33 >32 >31 >34

>32.6 >31.7 >32.2 >31.9

5th -- 95th percentile 24-Hour Urinary Protein (mg/24 Hours) Mean SD: First Trimester 80.0 60.6 Second Trimester 116.7 69.3 Third Trimester 115.3 69.2 VII. Metabolic Markers and Lipids: Amino acids are actively transported across the placenta, where they are used by the fetus for protein synthesis and as an energy source. In late pregnancy, the fetoplacental unit contains approximately 500 mg of protein. During pregnancy, fat stores are preferentially used as a substrate for fuel metabolism, and thus, protein catabolism is decreased. Plasma lipids and lipoproteins increase in pregnancy. A gradual two- to three-fold rise in triglyceride levels occurs by term and levels of 200 to 300 mg/dl are normal. Triglyceride concentrations return to normal by 8 weeks' postpartum even with lactation, but cholesterol and low-density lipoprotein levels remains elevated. The mechanisms for the pregnancy-induced changes in lipids are not completely understood, but appear to be partly caused by the elevated levels of estrogen, progesterone, and human placenta lactogen (hPL). 4-16 Weeks 3.21 16-24 Weeks 3.48 24-34 Weeks 3.49

Medians SD VIII. Hematologic Indices: Maternal blood volume begins to increase at about 6 weeks' gestation. Therefore, it increases progressively until 30 to 34 weeks and then plateaus until delivery. The average expansion of blood volume is 40 to 50%, although individual increases range from 20 to 100%. Women with multiple pregnancies have a larger increase in blood volume than those with singletons. The increase in blood volume results from a combined expansion of both plasma volume and red blood cell (RBC) mass. The peripheral white blood cell (WBC) count rises progressively during pregnancy. The traditional view of the immunologic system in pregnancy is that the fetus is a semi-allograft and a successful pregnancy is dependent on either evasion of immune surveillance or suppression of the maternal adaptive immune response. Red Blood Cell (RBC) Indices in Iron-Treated Women (66 mg Elemental Iron as Fumarate):

First trimester: 9-13 weeks; Second trimester: 19-22 weeks; Third trimester: 31-34 weeks; Term: 39-43 weeks. Mean cell volume (MCV); Mean corpuscular hemoglobin (MCH); Mean cell hemoglobin concentration (MCHC) <5th percentile shown as lower limit of normal. Platelet Count (109/L): First trimester (12 weeks) 240 (170-310) Third trimester (28 weeks) 250 (150-360) Term (38 weeks) 240 (140-370)

Median (5th- 95th percentile) White Blood Cell (WBC) Count (109/L) 18 Weeks 8.8 (5.6-13.8) 32 Weeks 9.7 (6.0-15.7) 39 Weeks 9.4 (5.8-15.1) Mean 1.96 x SD

Red blood cell count (1012/L) First trimester Second trimester Third trimester Term >3.45 >3.29 >3.23 >3.54

MCV, fl, 5th 95th percentile First trimester Second trimester Third trimester Term

88101 89104 90104 90102

Iron, Folate, and Vitamin B12 Levels: Mean Ferritin (ug/L) First trimester 46.8 2.5 Third trimester Term Mean TIBC (umol/L) First trimester 59.3 0.6 20.8 1.3 21.7 1.6

Measure Uric acid (mg/dL)

Term 4.72

Third trimester Term Folate (umol/L) First trimester Third trimester Term Vitamin B12 First trimester Third trimester Term

73.8 0.9 77.7 0.9

Factor VII

111 (60206) 103 (62169) 93 (46188) 125 (70224)

150 (80280) 115 (74177) 82 (66185) 125 (73214)

162 (84312) 123 (78194) 82 (34195) 115 (74179)

171 (87336) 127 (72208) 85 (39184) 115 (68194)

Thyroid diseases are common in women of childbearing age. However, normal pregnancy symptoms mirror those of thyroid disease, making it difficult to know when screening for thyroid disease is appropriate. In addition, the physiologic effects of pregnancy frequently make the interpretation of thyroid tests difficult. Therefore, it is important for obstetrician to be familiar with the normal changes in thyroid function that occur during pregnancy. TSH (mIU/L) and Free T4 (ng/dL) by Race (means, IQ range): Measure Black White

6.7 0.3 6.4 0.3 6.9 0.4

Factor X

Factor V

345.6 8.9 259.3 6.0 241.8 6.5

Factor II

(% of standards shown, mean and range) Coagulation Parameter in Normal Pregnancy and Puerperium (n = 117): 20 10 Weeks Weeks 0.97 0.08 27.0 2.7 412.5 69.5 101.5 12.7 99.4 21.3 64.1 15.8 0.91 0.06

First trimester: mean 12.6 weeks; Third trimester: 32 weeks; Term: 38 weeks Total Iron Binding Capacity (TIBC) Fasting Homocysteine With and Without Folic Acid Supplementation (Various Doses) (umol/L): Measure 8 Weeks 20 Weeks 32 Weeks

First Trimester TSH 0.9 (0.4-1.6) 1.3 (0.8-2.0) Free T4 1.0 (0.9-1.1) 1.0 (0.9-1.1) Second Trimester TSH 1.0 (0.6-1.5) 1.6 (1.0-2.2) Free T4 0.9 (0.8-1.0) 0.9 (0.8-1.0) Third Trimester TSH 1.2 (0.9-1.9) 1.5 (1.4-2.1) Free T4 0.8 (0.7-0.9) 0.8 (0.7-0.9) Delivery TSH Free T4

Measure

30 Weeks 36 Weeks 0.88 0.07 0.87 0.07

INR

Unsupplemented 6.48 1.30 5.22 1.29 5.16 1.32 Supplemented 6.32 1.34 4.18 1.32 4.42 1.37 Means 1 SD IX. Coagulation Factors and Parameters: Pregnancy places women at a 5 to 6 fold increased risk for thromboembolic disease. This greater risk is caused by increased venous stasis, vessel wall injury, and changes in the coagulation cascade that leads to hypercoagulability. In pregnancy, several procoagulant coagulation factors are increased, and changes occur to some of the natural inhibitors of coagulation. In addition, pregnancy causes a decrease in the fibrinolytic system with reduced levels of available circulating plasminogen activator inhibitor (PAI-1). These physiologic changes provide defense against peripartum hemorrhage. Coagulation Factors: 11-15 Weeks 21-25 Weeks 31-35 Weeks 36-40 Weeks PTT (sec) Fibrinogen (mg %) Antithrombin III

26.9 2.7 27.1 2.9 27.5 2.8 463.9 83.9 101.4 10.3 107.5 24.9 62.1 14.2 538.8 107.3 104.2 12.5 99.3 26.0 54.0 13.3 556.9 113.3 102.8 13.5 94.9 25.5 51.7 17.9

2.1 (1.3-3.1) 2.8 (2.0-4.4) 0.8 (0.7-0.9) 0.8 (0.7-0.9)

Protein C (%)

Screening and Diagnostic Thresholds across Pregnancy. TSH >2.5 mIU/L -- requires further workup for hypothyroidism. Total T4 <100 nmol/L (7.8 /dL) -diagnostic of hypothyroidism. Thyroxine (T4); ThyroidStimulating Hormone (TSH). Sequential Measurements of Plasma CRH, ACTH, Cortisol, Aldosterone and Urinary Free Cortisol during Pregnancy: Urinar y Free Cortis Cortis Weeks CRH ACTH ol ol DHEA Aldostero of S ne Gestatio (PG/M (PG/M (G/D (G/2 n L) L) L) (/DL) (PG/ML) 4 H)

Protein S (%)

PAI (AU/ml) 10.3 4.7 11.3 5.0 20.5 7.3 22.4 7.5 International Normalized Ratio (INR); Plasminogen Activator Inhibitor (PAI); Partial Thromboplastin Time (PTT). Mean SD X. Endocrine Changes and Parameters:

Measure

11-15

115 56 145 30

8.8 2.8 9.8 1.5

10.5 102 54.8 1.4 14 412 63.6 7.3 20.0 85.1 84.4 1.1 9.0 487 42.8 8.4 105 8.8 111 8.7

placental weight averages 450 g, representing approximately one seventh (one sixth with cord and membranes) of fetal weight. Mean amniotic fluid volume increases from 250 to 800 ml between 16 and 32 weeks, and decreases to 500 ml at term. Fetal urine production ranges from 400 to 1,200 ml/day and is the primary source of amniotic fluid. The fetal umbilical circulation receives approximately 40% of fetal combined ventricular output (300 ml/mg/min). Umbilical blood flow is 70 to 130 ml/min after 30 weeks' gestation. Fetal cardiac output is constant over a heart rate range of 120 to 180 bpm. The fetus exists in a state of aerobic metabolism, with arterial Po2 values in the 20- to 25- mm Hg range. Approximately 20% of the fetal O2 consumption of 8 ml/kg/min is required in the acquisition of new tissue. The maternal environment during pregnancy (e.g., under-nutrition) may have significant long-term effects, because growth-restricted offspring demonstrate an increased risk of adult metabolic syndrome. Umbilical Cord Blood at Delivery: Measure pH Artery Vein

Reticulocyte count (109/L)

145.8 -- 192.6

25th -- 75th percentile

21-25

31-35

1,570 12.1 22.0 62.6 349 2.0 1.2 6.8 766 94 4,346 18.6 26.0 63.8 754 2.6 1.1 7.1 1,150 170

36-40

Adrenocorticotrophic Hormone (ACTH); Corticotrophinreleasing Hormone (CRH); Dehydroepiandrosterone (DHEAS). Calcium Metabolism: 13-16 Weeks 21-24 Weeks 29-32 Weeks >37 Weeks 2.052.25

Measure Total Calcium (mmol/L)

2.25-2.35 2.15-2.30 2.10-2.25

Ionized Calcium (mmol/L) 1.10-1.20 1.05-1.20 1.10-1.15 1.05-1.15 ( 1 SD) 8-11 Weeks 73-101 20-23 Weeks 79-108 28-31 Weeks 87-113 >37 Weeks 83-109

7.06 -- 7.36 7.14 -- 7.45 27.8 -- 68.3 24.0 -- 56.3 9.8 -- 41.2 12.3 -- 45.0

Pco2 (mm Hg) Po2 (mm Hg)

Measure Calcitonin (ng/L) Parathyroid hormone (ng/L) 1,25 Dihydroxy Vitamin D (ng/L)

Base deficit (mmol/L) 0.5 -- 15.3 0.07 -- 12.6

7-15

4.5-12

5-15

10-17

White blood cell count (109/L) 11.1 -- 16.2 Red cell count (1012/L) Hemoglobin (g/dL) Hematocrit (%) MCV (fl) Platelet count (109/L) 4.13 -- 4.62 15.3 -- 17.2 45.2 -- 50.9 107.4 -- 113.3 237 -- 321

58-78

94-122

98-136

94-150

XI. Umbilical Cord Blood / Fetal Physiology: The fetus develops within a complex milieu and is wholly dependent on its mother for nutrients. Pregnancyassociated cardiovascular changes include a doubling of maternal cardiac output and a 40% increase in blood volume. Uterine blood flow at term averages 750 ml/min, or 10 to 15% in maternal cardiac output. Normal term