Pediatric 3 Flashcards
CHF
Classification
Ross Classification
Classification:
NYHA
Class I Asymptomatic
No limitation to ordinary physical activity-no fatigue, dyspnea or palpitation.
Class II Mild-limitation of physical activity Unable to climb stairs.
Class III Moderate-Marked limitation
Shortness of breath on walking on flat surface.
Class IV Severe-Orthopnea-breathless even at rest No physical activity is possible
Ross Classification:
Heart failure in infants Mild
Intake < 3.5 oz/feed and time of feeding less than 20min Respiratory rate less than 50bpm HR less than 160bpm Normal perfusion mild Hepatomegaly (2cmbelow costal margin)
CHF
Causes
Causes
The heart failure syndrome may arise from diverse causes. The most common causes of CHF in infancy are CHDs. Beyond infancy, myocardial dysfunction of various etiologies is an important cause of CHF. Tachyarrhythmias and heart block can also cause heart failure at any age.
- Congenital heart disease
a-Volume overload lesions such as VSD, PDA, and ECD are the most common causes of CHF in the first 6 months of life.
b. Large L-R shunt lesions, such as VSD and PDA, do not cause CHF before 6 to 8 weeks of age because the pulmonary vascular resistance (PVR) does not fall low enough to cause a large shunt until this age. CHF may occur earlier in premature infants (within the first month) because of an earlier fall in the PVR.
c. Children with TOF do not develop CHF and that ASDs rarely cause CHF in the pediatric age group, although they can cause CHF in adulthood. 2. Acquired heart disease.
Acquired heart disease of various etiologies can lead to CHF. Common entities (with the approximate time of onset of CHF) are as follows.
a-Viral myocarditis (in toddlers, occasionally in neonates with fulminating course)
b. Myocarditis associated with Kawasaki disease (1 to 4 years of age).
c. Acute rheumatic carditis (in school-age children).
d. Rheumatic valvular heart diseases, such as MR or AR (older children and adults).
e. Dilated cardiomyopathy (at any age during childhood and adolescence).
f. Doxorubicin cardiomyopathy (months to years after chemotherapy).
g. Cardiomyopathies associated with muscular dystrophy and Friedreich’s ataxia (in older children and adolescents). 3. Miscellaneous causes
a-Metabolic abnormalities (severe hypoxia, acidosis, hypoglycemia, hypocalcemia) in newborns)
b. Hyperthyroidism (at any age)
c. Supraventricular tachycardia (SVT) (in early infancy)
d. Complete heart block associated with CHDs (in the newborn period or early infancy)
e. Severe anemia (at any age), hydrops fetalis (neonates), and sicklemia (childhood and adolescence)
f. Bronchopulmonary dysplasia (BPD) with right-sided failure (the first few months of life)
g. Primary carnitine deficiency (2-4 years)
h. Acute cor-pulmonary caused by acute airway obstruction (during early childhood)
i. Acute systemic hypertension with glomerulonephritis (school-age children)
CHF
Dx
Diagnosis of CHF
The diagnosis of CHF relies on several sources of clinical findings, including history, physical examination, chest radiographs, and echo studies. There is no single laboratory test that is diagnostic of CHF in pediatric patients.
1-Poor feeding of recent onset, tachypnea, poor weight gain, and cold sweat on the forehead suggest CHF in infants. In older children, shortness of breath, especially with activities, easy fatigability, puffy eyelids, or swollen feet may be presenting complaints
- Physical findings can be divided by pathophysiologic subgroups.
a-Compensatory responses to impaired cardiac function.
(1) Tachycardia, gallop rhythm, weak and thready pulse, and cardiomegaly on chest radiographs.
(2) Signs of increased sympathetic discharges (growth failure, perspiration, and cold wet skin).
b. Signs of pulmonary venous congestion (left-sided failure) include tachypnea, dyspnea on exertion (or poor feeding in small infants), orthopnea in older children, and rarely wheezing and pulmonary crackles
c. Signs of systemic venous congestion (right-sided failure) include hepatomegaly and puffy eyelids. Distended neck veins and ankle edema are not seen in infants. 4-The ECG is not helpful in deciding whether the patient is in CHF, although it may be helpful in determining the cause.
- Echo studies confirm the presence of chamber enlargement or impaired LV function and help determine the cause of CHF.
- Increased levels of plasma natriuretic peptides (atrial natriuretic peptide [ANP] and B-type natriuretic peptide [BNP]) are helpful in differentiating causes of dyspnea (lungs vs. heart) in adult patients, but the usefulnes of the levels of these peptides is limited in pediatric use. Plasma levels of these peptides are normally elevated in the first weeks of life.
- Endomyocardial biopsy obtained during cardiac catheterization offers a new approach to specific diagnosis of the cause of CHF, such as inflammatory disease, infectious process, or metabolic disorder.
CHF
MGX
Management
The treatment of CHF consists of
(1) elimination of the underlying causes or correction of precipitating or contributing causes (e.g., infection, anemia arrhythmias, fever, hypertension)
(2) general supportive measures
(3) control of heart failure state by use of drugs, such as inotropic agents, diuretics, or afterloadreducing agents.
Treatment of underlying causes or contributing factors.
1.Treatment or surgery of underlying CHDs or valvular heart disease when feasible (the best approach for complete cure).
(-).Antihypertensive treatment for hypertension.
(-). Antiarrhythmic agents or cardiac pacemaker therapy for arrhythmias or heart block.
- General measures.
a. Nutritional supports are important. Infants in CHF need significantly higher caloric intakes than recommended for average children. The required calorie intakes may be as high as 150 to 160 kcal/kg/day for infants in CHF.
b. Increasing caloric density of feeding may be required and it may be accomplished with fortification of feeding .Frequent small feedings are better tolerated than large feedings in infants.
c. If oral feedings are not well tolerated, intermittent or continuous nasogastric (NG) feeding is indicated. To promote normal development of oral-motor function, infants may be allowed to take calorie-dense oral feeds throughout the day and then be given continuous NG feeds overnight.
d. For older children with heart failure, salt restriction (<0.5 g/day) and avoidance of salty snacks (chips, pretzels) and table salt are recommended. Bed rest remains an important component of management.
The availability of a television and computer games for entertainment assures bed rest in older children. Drug therapy. Three major classes of drugs are commonly used in the treatment of CHF in children: inotropic agents, diuretics, and afterload-reducing agents.
Diuretics.
Diuretics remain the principal therapeutic agent to control pulmonary and systemic venous congestion. Diuretics only reduce preload and improve congestive symptoms, but do not improve cardiac output or myocardial contractility .Three classes of diuretics are available.
a-Thiazide diuretics (e.g., chlorothiazide, hydrochlorothiazide),which act at the proximal and distal tubules, are no longer popular.
b) Rapid-acting diuretics (e.g., furosemide, ethacrynic acid) are the drugs of choice. They act primarily at the loop of Henle (“loop diuretics”).
(c) Aldosterone antagonist (e.g., spironolactone) acts on the distal tubule to inhibit sodium-potassium exchange. These drugs have value in preventing hypokalemia produced by other diuretics and thus are used in conjunction with a loop diuretic. However, when ACE inhibitors are used, spironolactone should be discontinued to avoid hyperkalemia.
(2) The main side effects of diuretic therapy are hypokalemia (except when used with spironolactone) and hypochloremic alkalosis. Digitalis glycosides.
Digoxin increases the cardiac output (or contractile state of the myocardium), thereby resulting in an upward and leftward shift of the ventricular function curve relating cardiac output to filling volume of pressure . Use of digoxin in infants with large L-R shunt lesions (e.g., large VSD) is controversial because ventricular contractility is normal in this situation. However, studies have shown that digoxin improves symptoms in these infants, perhaps because of other actions of digoxin, such as parasympathomimetic action and diuretic action. (2) Dosage of digoxin. The total digitalizing dose (TDD) and maintenance dosage of digoxin by oral and intravenous routes . The maintenance dose is more closely related to the serum digoxin level than is the digitalizing dose, which is given to build a sufficient body store of the drug and to shorten the time required to reach the pharmacokinetic steady state.
(3) How to digitalize.
a-One half the total digitalizing dose is followed by one fourth and then the final one fourth of the total digitalizing dose at 6- to 8-hour intervals. The maintenance dose is given 12 hours after the final total digitalizing dose. This results in a pharmacokinetic steady state in 3 to 5 days.
(b) When an infant is in mild heart failure, the maintenance dose may be administered orally without loading doses; this results in a steady state in 5 to 8 days.
(c) A baseline ECG (rhythm and PR interval) and serum electrolytes are recommended. Hypokalemia and hypercalcemia predispose to digitalis toxicity
Monitoring for digitalis toxicity.
Monitoring for digitalis toxicity.
a-With the relatively low dosage recommended digitalis toxicity is unlikely unless there are predisposing factors for the toxicity. Predisposing factors for digitalis toxicity may include renal disease, premature infants, hypothyroidism, myocarditis, electrolyte imbalance (hypokalemia and hypercalcemia), alkalosis, and catecholamine administration.
(b) Serum digoxin levels obtained during the first 3 to 5 days after digitalization tend to be higher than those obtained when the pharmacokinetic steady state is reached. Therefore, detection of digitalis toxicity is best accomplished by monitoring with ECGs, not by serum digoxin levels during this period.
(c) ECG signs of digitalis toxicity involve disturbances in the formation and conduction of the impulse, while those of digitalis effect are confined to ventricular repolarization. First-degree (or second- degree) AV block, profound sinus bradycardia or sinoatrial block, supraventricular arrhythmias (atrial or junctional ectopic beats and tachycardias), and, rarely, ventricular arrhythmias are all possible signs of toxicity. Shortening of QTc and diminished amplitude of the T wave are the signs of digitalis effect.
Serum digoxin levels.
Serum digoxin levels.
Therapeutic ranges of serum digoxin levels for treating CHF are 0.8 to 2 ng/mL.
Blood for serum digoxin levels should be drawn just before a scheduled dose or at least 6 hours after the last dose; samples obtained earlier than 6 hours after the last dose will give a falsely elevated level.
Digitalis toxicity. The diagnosis of digitalis toxicity is based on the following clinical and laboratory findings.
a-A history of accidental ingestion.
(b) Non-cardiac symptoms in digitalized children: anorexia, nausea, vomiting, diarrhea, restlessness, drowsiness, fatigue, and visual disturbances in older children.
(c) ECG signs of toxicity (as described previously).
(d) An elevated serum level of digoxin (>2 mg/mL) in the presence of clinical findings suggestive of digitalis toxicity.
Afterload-reducing agents.
Afterload-reducing agents.
1-Reducing afterload tends to augment the stroke volume without a great change in the inotropic state of the heart and therefore without increasing myocardial oxygen consumption. Combined use of an inotropic agent, a vasodilator, and a diuretic produces most improvement in both inotropic state and congestive symptoms
(2) Afterload-reducing agents may be used not only in infants with a large-shunt VSD, AV canal, or PDA, but also in patients with dilated cardiomyopathies, myocardial ischemia, postoperative cardiac status, severe MR or AR, and systemic hypertension
CHF
other drugs
Surgery
Other drugs.
(-)β-Adrenergic blockers
a-As reported in adults, β-adrenergic blockers have been shown to be beneficial in some pediatric patients with chronic CHF, who were treated with standard anticongestive drugs. Adrenergic overstimulation, often seen in patients with chronic CHF, may have detrimental effects on the failing heart by inducing myocyte injury and necrosis. However, β-adrenergic blockers should not be given to those with decompensated heart failure.
(b) When added to standard medical therapy for CHF, carvedilol (a nonselective β-adrenergic blocker with additional α1-antagonist activities) has been shown to be beneficial in children with idiopathic dilated cardiomyopathy ,chemotherapy- induced cardiomyopathy, postmyocarditis myopathy, muscular dystrophy, or postsurgical heart failure(e.g., Fontan operation) (c) Metoprolol was also beneficial in dilated cardiomyopathy.
(d) Propranolol added to conventional treatment for CHF was also beneficial in a small number of infants with large L-R shunts at the dose of 1.6 mg/kg per day.
(-)Carnitine.
Carnitine, which is an essential cofactor for transport of long-chain fatty acids into mitochondria for oxidation, has been shown to be beneficial in some cases of dilated cardiomyopathy. The dosage of L-carnitine used was 50-100 mg/kg/day, given BID or TID orally (maximum daily dose 3 g).
(-)Surgical management. If medical treatment as outlined previously does not improve CHF caused by CHD within a few weeks to months, one should consider either palliative or corrective cardiac surgery for the underlying cardiac defect when technically feasible. Captopril (Capoten) Oral:
Newborn: 0.1-0.4 mg/kg, TID-QID May cause hypotension, dizziness, neutropenia, and proteinuria
Infant: Initially 0.15-0.3 mg/ kg, QD-QID. Titrate upward if needed. Max dose 6 mg/kg/24 hr.
Dose should be reduced in patients with impaired renal function
Child: Initially 0.3-0.5 mg/kg, BIDTID. Titrate upward if needed.
Max dose 6 mg/kg/24 hr.
Adolescents and adults:
Initially 12.5-25 mg, BID-TID. Increase weekly if needed by 25 mg/dose to max dose 450 mg/24 hr.
Enalapril (Vasotec)
SUGGESTED STARTING DOSAGES OF CATECHOLAMINES DRUG DOSAGE AND ROUTE SIDE EFFECTS
SUGGESTED STARTING DOSAGES OF CATECHOLAMINES DRUG DOSAGE AND ROUTE SIDE EFFECTS
Epinephrine (Adrenalin) 0.1-1 µg/kg/min IV Hypertension, arrhythmias
Isoproterenol (Isuprel) 0.1-0.5 µg/kg/min IV Peripheral and pulmonary vasodilatation
Dobutamine (Dobutrex) 2-8 µg/kg/min IV Little tachycardia and vasodilatation, arrhythmias
Dopamine (Intropin) 5-10 µg/kg/min IV Tachycardia, arrhythmias, hypertension or hypotension Dose-related cardiovascular effects (µg/kg/min):
Renal vasodilatation: 2-5 Inotropic: 5-8 Tachycardia: >8 Mild vasoconstriction: >10 Vasoconstriction: 15-20
DIURETIC AGENTS AND DOSAGES PREPARATION ROUTE DOSAGE
DIURETIC AGENTS AND DOSAGES PREPARATION ROUTE DOSAGE
THIAZIDE DIURETICS
Chlorothiazide (Diuril) Oral 20-40 mg/kg/day in 2 to 3 divided doses Hydrochlorothiazide (HydroDIURIL) Oral 2-4 mg/kg/day in 2 to 3 divided doses LOOP DIURETICS
Furosemide (Lasix) IV 1 mg/kg/dose Oral 2-3 mg/kg/day in 2 to 3 divided doses Ethacrynic acid (Edecrin) IV 1 mg/kg/dose Oral 2-3 mg/kg/day in 2 to 3 divided
doses
ALDOSTERONE ANTAGONIST
Spironolactone (Aldactone) Oral 1-3 mg/kg/day in 2 to 3 divided doses
Sinus Tachycardia (vs.) Sinus Bradycardia
Sinus Tachycardia
Characteristics of sinus rhythm are present . The rate is faster than the upper limit of normal for age .A rate greater than 140 beats/minute in children and greater than 170 beats/minute in infants may be significant. The heart rate is usually less than 200 beats/minute in sinus tachycardia
Causes
Anxiety, fever, hypovolemia or circulatory shock, anemia, congestive heart failure (CHF), administration of catecholamines, thyrotoxicosis, and myocardial disease are possible causes.
Significance
Increased cardiac work is well tolerated by healthy myocardium.
Management
The underlying cause is treated
Sinus Bradycardia
Description The characteristics of sinus rhythm are present (see previous description), but the heart rate is slower than the lower limit of normal for the age .A rate slower than 80 beats/minute in newborn infants and slower than 60 beats/minute in older children may be significant
Causes
Sinus bradycardia may occur in normal individuals and trained athletes. It may occur with vagal stimulation, increased intracranial pressure, hypothyroidism, hypothermia, hypoxia, hyperkalemia, and administration of drugs such as digitalis and β-adrenergic blockers.
Significance
In some patients, marked bradycardia may not maintain normal cardiac output.
Management
The underlying cause is treated.
SVT
Supraventricular Tachycardia
The heart rate is extremely rapid and regular (usually 240 ± 40 beats/minute).
Causes
1-No heart disease is found in about half of patients. This idiopathic type of SVT occurs more commonly in young infants than in older children.
2-WPW preexcitation is present in 10% to 20% of cases, which is evident only after
conversion to sinus rhythm.
3-Some congenital heart defects (e.g., Ebstein’s anomaly, single ventricle, and congenitally corrected transposition of the great arteries) are more susceptible to this arrhythmia.
4-SVT may occur following cardiac surgeries.
Significance
SVT may decrease cardiac output and result in CHF.
Management
Non medical therapy
Vagal stimulatory maneuvers (unilateral carotid sinus massage, gagging, and pressure on an eyeball) may be effective in older children but are rarely effective in infants. Placing an ice-water bag on the face (for up to 10 seconds) is often effective in infants (by diving reflex).
Medical Therapy
1-Adenosine is considered the drug of choice. It has negative chronotropic, dromotropic, and inotropic actions with a very short duration of action (half-life <10 seconds) and minimal hemodynamic consequences.
Adenosine is effective for almost all reciprocating SVT (in which the AV node forms part of the reentry circuit) and for both narrow- and wide-complex regular tachycardia. It is not effective for irregular tachycardia.
It is not effective for non-reciprocating atrial tachycardia, atrial flutter or fibrillation, and ventricular tachycardia, but it has differential diagnostic ability. Its transient AV block may unmask atrial activities by slowing the ventricular rate and thus help to clarify the mechanism of certain supraventricular arrhythmias.
Adenosine is given by rapid IV bolus followed by a saline flush, starting at 50 µg/kg, increasing in increments of 50 µg/kg every 1 to 2 minutes. The usual effective dose is 100 to 150 µg/kg with maximum dose of 250 µg/kg 3. If the infant is in severe CHF, emergency treatment is directed at immediate cardioversion. The initial dose of 0.5 joule/kg is increased in steps up to 2 joule/kg.
- Esmolol, other β-adrenergic blockers, verapamil, and digoxin have also been used with some success. Intravenously administered propranolol has been commonly used to treat SVT in the presence of WPW syndrome. IV verapamil should be avoided in infants younger than 12 months because it may produce extreme bradycardia and hypotension in infants.
- For postoperative atrial tachycardia (which requires rapid conversion), IV amiodarone may provide excellent results. The side effects may include hypotension, bradycardia, and decreased left ventricular (LV) function. 6. Overdrive suppression (by transesophageal pacing or by atrial pacing) may be effective in children who have been digitalized.
- Radiofrequency catheter ablation or surgical interruption of accessory pathways should be considered if medical management fails or frequent recurrences occur. Radiofrequency ablation can be carried out with a high degree of success, a low complication rate, and a low recurrence rate
After termination of SVT send child for
1- ECG to exclude prexcitation syndrome
2- Echo for structural heart disease as cardiomyopathy and Ebstien anomaly, and ASD, cardiac tumor,LTGA
3- Thyroid function test and serum electrolyte
Prevention of Recurrence of SVT
1-In infants without WPW preexcitation, oral propranolol for 12 months is effective. Verapamil can also be used but it should be used with caution in patients with poor LV function and in young infants.
2- In infants in CHF and ECG evidence of WPW preexcitation, one may start with digoxin (just to treat CHF), but digoxin should be switched to propranolol when the infant’s heart failure improves.
3- In infants or children with WPW preexcitation on the ECG, propranolol or atenolol is used in the long-term management. In the presence of WPW preexcitation, digoxin or verapamil may increase the rate of antegrade conduction of the impulse through the accessory pathway and should be avoided
Heart block
Heart block
First-Degree Atrioventricular Block Description The PR interval is prolonged beyond the upper limits of normal for the patient’s age and heart rate
Causes
First-degree AV block can appear in otherwise healthy children and young adults, particularly in athletes. Other causes include congenital heart diseases (such as endocardial cushion defect, atrial septal defect, Ebstein’s anomaly), infectious disease, inflammatory conditions (rheumatic fever), cardiac surgery, and certain drugs (such as digitalis, calcium channel blockers).
Significance
First-degree AV block does not produce hemodynamic disturbance. It sometimes progresses to a more advanced AV block.
Management.
No treatment is indicated, except when the block is caused by digitalis toxicity Second-Degree Atrioventricular Block MOBITZ TYPE I Description.
The PR interval becomes progressively prolonged until one QRS complex is dropped completely Causes.
Mobitz type I AV block appears in otherwise healthy children. Other causes include myocarditis, cardiomyopathy, myocardial infarction, congenital heart defect, cardiac surgery, and digitalis toxicity.
Significance.
The block is at the level of the AV node. It usually does not progress to complete heart block.
Management.
The underlying causes are treated. MOBITZ TYPE II Description.
The AV conduction is “all or none.” AV conduction is either normal or completely blocked Causes.
Causes are the same as for Mobitz type I.
Significance.
The block is at the level of the bundle of His. It is more serious than type I block because it may progress to complete heart block Management.
The underlying causes are treated. Prophylactic pacemaker therapy may be indicated Third-Degree Atrioventricular Block Description.
In third-degree AV block (complete heart block), atrial and ventricular activities are entirely independent of each other and the P waves are regular (regular P-P interval), with atrial rate comparable to the normal heart rate for the patient’s age. The QRS complexes are also regular (regular R-R interval), with a rate much slower than the P rate.
In congenital complete heart block, the duration of the QRS complex is normal because the pacemaker for the ventricular complex is at a level higher than the bifurcation of the bundle of His. The ventricular rate is faster (50 to 80 beats/minute) than that in the acquired type, and the ventricular rate is somewhat variable in response to varying physiologic conditions.
In surgically induced or acquired (after myocardial infarction) complete heart block, the QRS duration is prolonged because the pacemaker for the ventricular complex is at a level below the bifurcation of the bundle of His. The ventricular rate is in the range of 40 to 50 beats/minute (idioventricular rhythm) and the ventricular rate is relatively fixed. Causes
Congenital Type.
Causes are an isolated anomaly (without associated structural heart defect), structural heart disease such as congenitally corrected transposition of the great arteries, or maternal diseases such as systemic lupus erythematosus, Sjögren’s syndrome, or other connective tissue disease.
Acquired Type.
Cardiac surgery is the most common cause of acquired complete heart block in children. Other rare causes include severe myocarditis. Lyme carditis, acute rheumatic fever, mumps, diphtheria, cardiomyopathies, tumors in the conduction system, overdoses of certain drugs, and myocardial infarction. These causes produce either temporary or permanent heart block. Significance
Congestive heart failure (CHF) may develop in infancy, particularly when there are associated congenital heart defects.
Patients with isolated congenital heart block who survive infancy are usually asymptomatic and achieve normal growth and development for 5 to 10 years. Chest x-ray films may show cardiomegaly.
Syncopal attacks (Stokes-Adams attacks) may occur with a heart rate below 40 to 45 beats/minute. A sudden onset of acquired heart block may result in death unless treatment maintains the heart rate in the acceptable range. Management
Atropine or isoproterenol is indicated in symptomatic children and adults until temporary ventricular pacing is secured.
A temporary transvenous ventricular pacemaker is indicated in patients with heart block, or it may be given prophylactically in patients who might develop heart block.
No treatment is required for children with asymptomatic congenital complete heart block with acceptable rate, narrow QRS complex, and normal ventricular function.
Ventricular tachycardia(VT)
Ventricular tachycardia(VT)
The differential diagnosis of tachycardias with a prolonged QRS includes ventricular tachycardias, pre-excited supraventricular tachycardias and any other tachycardia conducted aberrantly owing to fixed, functional, or rate-related bundle branch block.
Additionally, pacemaker-mediated tachycardia (a wide complex tachycardia with paced QRS morphology) should be considered in patients with implanted pacemakers
The hallmark electrocardiographic features of ventricular tachycardia are prolonged QRS duration and dissociation of the P waves from QRS during tachycardia
Tachycardias with prolonged QRS duration should be considered ventricular tachycardia and treated as such until a more definitive diagnosis can be established Symptoms caused by ventricular tachycardia vary widely, and the clinical presentation itself is of little benefit in distinguishing these tachycardias from SVT with aberrant conduction. Patients may present with modest symptoms comparable to those experienced during various supraventricular tachycardias or may experience cardiac arrest and sudden death. Likewise, successful termination using interventions such as vagal maneuvers, adenosine, atrial pacing, or verapamil should not be construed as evidence of a supraventricular mechanism Non-sustained (defined as more than 3 but <30 consecutive ventricular depolarizations) versus sustained or self-limited, and spontaneous versus induced (such as with programmed stimulation) are used. Ventricular tachycardias may also be characterized as monomorphic or polymorphic, depending on the constancy or variation of QRS complexes during tachycardia Two specific types of polymorphic ventricular tachycardia are torsades de pointes and bidirectional ventricular tachycardia . The former, by definition, is associated with prolongation of the QT interval, as occurs in congenital and acquired long QT syndromes, and the QRS complexes appear to undulate or twist about the isoelectric line as the QRS morphology gradually changes
shape and axis. Bidirectional ventricular tachycardia is described in association with digitalis toxicity(pathognomonic ), Andersen-Tawil syndrome, or catecholaminergic polymorphic ventricular tachycardia (CPVT). As the name suggests, beat-tobeat alternation in the QRS axis occurs during ongoing tachycardia, a phenomenon that easily can be mistaken for ventricular bigeminy Acute management If unstable, synchronized cardioversionis started at 2J/kg and repeated, increasing the dose if needed.
If stable, may attempt amiodarone at 5mg/kg IV over 30–60 minutes or procainimide at 15mg/kg IV over 30–60 minutes.
Further work-up and disposition
History should focus on prior symptoms, symptoms suggestive of myocarditis or long-standing cardiomyopathy, and the possibility of drug toxicity, as well as a thorough family history for known arrhythmias or history of sudden death.
Once in normal sinus rhythm, repeat EKG to rule out underlying abnormalities including long QT, Brugada, arrhythmogenic right ventricular cardiomyopathy, structural heart disease, electrolyte abnormalities and ischemia.
Laboratory work-up should include toxicology screen, serum electrolytes, complete blood count, viral panel, blood culture and cardiac enzymes.
Cardiac consultation and echocardiographic evaluation are done to rule underlying structural heart disease, cardiomyopathy, cardiac tumors.
Admit for observation.
After cardioversion, return to sinus rhythm may be transient and continual infusion of amiodarone may be required.
For recurrent VT need ICD implantation
Long QT syndrome
Long QT syndrome
The congenital long QT syndrome is a genetic disorder of prolonged cardiac repolarization that may cause cardiac arrest and sudden death. Abnormalities in cardiac ion channels predispose patients to a characteristic polymorphic VT called “torsades de pointes”. Events are often precipitated by adrenergic stimuli. Acquired long QT may also occur and can be caused by drugs, underlying medical conditions or electrolyte imbalances.
Clinical features Patients may present with presyncope, syncope, seizures, or cardiac arrest.
Precipitating factors may include exercise, especially swimming, emotional stress, exposure to loud noises of telephone or clock alarm or even sleep.
Although rare, infants can present with poor feeding, or with episodes of lethargy, cyanosis or poor perfusion. causes
Congenital
1-Romano-Ward syndrome (autosomal dominant form). This more common form occurs in people who inherit only a single gene variant from one parent.
2-Jervell and Lange-Nielsen syndrome (autosomal recessive form). This rare form usually occurs earlier and is more severe. In this syndrome, children receive the faulty gene variants from both parents. The children are born with long QT syndrome and deafness. Acquired
Medication
1-certain common antibiotics, such as erythromycin (Eryc, Erythrocin, others), azithromycin (Zithromax, Zmax) and others
2-Certain antifungal medications taken by mouth used to treat yeast infections
3-Diuretics that cause an electrolyte imbalance (low potassium, most commonly)
4-Heart rhythm drugs (especially anti-arrhythmic medications that lengthen the QT interval)
5-Certain antidepressant and antipsychotic medications
6-Some anti-nausea medications Other cause
1- Low potassium level (hypokalemia)
2-Low calcium level (hypocalcemia)
3-Low magnesium level (hypomagnesemia)
4-COVID-19 infection Electrocardiogram findings Sinus rhythm ECG, QTc of >460 in post-pubertal females and 450 in others, best obtained from lead II (Bazett Formula QTc= QT Interval/√-RR). Borderline QTc>440 ms in the setting of clinical symptoms and/or family history should be investigated.
Abnormal T wave morphology including notching and low amplitude. Torsade de pointes seen during events.
Acute management For torsades de pointes, perform emergent defibrillation followed by administration of magnesium sulfate and possibly lidocaine. Correct underlying problem if acquired long QT.
Intravenous beta-blockade may calm an adrenergic storm.
For congenital type ICD implantation Further work-up and management in suspected congenital long QT syndrome
Obtain thorough family history of rhythm abnormalities, sudden death, deafness.
Ascertain all medications.
Review history of event that may have triggered arrhythmia.
Obtain electrolytes and treat underlying abnormalities.
If presented with symptoms or documented VT, admit for observation, cardiology consultation and treatment.
For patients presenting with non-cardiac issues and noted to have abnormal QTc interval, out-patient cardiology follow-up may be arranged.
Restrict all strenuous activity pending cardiology follow-up. Prognosis Prognosis is poor in untreated symptomatic patients, with an annual mortality of 20%. B-blockers are the mainstream therapy and reduce risk of sudden death to about 6% annually but do not eliminate it completely. High risk patients may benefit from ICD placement which has been shown to reduce mortality risk. Factors known to increase risk include history of previous syncope, deafness, previous torsade, female gender and genotype. Risk factors
The following things may increase your risk of developing congenital or acquired long QT syndrome or its symptoms:
-A history of cardiac arrest
-Having a first-degree relative (parent, sibling) with long QT syndrome
-Using medications known to cause prolonged QT intervals
-Being female and on heart medication
-Excessive vomiting or diarrhea
-Eating disorders, such as anorexia nervosa, which cause electrolyte imbalances
Pregnancy and delivery aren’t associated with an increased risk of symptoms in women diagnosed with long QT syndrome. However, if you have the condition and are pregnant, your doctor will want to carefully monitor you during and after pregnancy.
TOF
definition
History
Cf
Examination
Ix
Natural History
Tetralogy of Fallot:
TOF occurs in 5% to 10% of all congenital heart defects. This is probably the most common cyanotic heart defect. TOF included the following four abnormalities:
❶ VSD (large, mal alignment, overriding on aorta)
❷ right ventricular outflow tract (RVOT) obstruction,
❸ RVH,
and ❹ overriding of the aorta. (Here aorta open to two chamber and receive blood from left and right side )
Right aortic arch is present in 25% of cases
Types :-
- classical TOF
- pink TOF
pv stenosis is mild so high blood flow on lung
Cyanosis depend on pulmonary valve.
- TOF + PV atresia
Present : Sever Cyanosis immediately after birth . Here blood come from PDA or collateral.
- TOF with absent of pulmonary valve
fusion of the leaflets, but with small Opening in between causing 2 problems stenosis and regurgitation causing aneurysm dilatation of the pulmonary artery and its branches and compression on alveoli and bronchi so present as chesty .
CLINICAL MANIFESTATIONS :-
HISTORY
1-A heart murmur is audible at birth.
2-Dyspnea on exertion, squatting, or hypoxic spells develop later, even in mildly cyanotic infants
3-Occasional infants with acyanotic TOF may be asymptomatic or may show signs of CHF from large left-to-right ventricular shunt.
4-Immediately after birth, severe cyanosis is seen in patients with TOF and pulmonary atresia.
PHYSICAL EXAMINATION
1-Varying degrees of cyanosis, tachypnea, and clubbing (in older infants and children) are present.
2-An RV tap along the left sternal border and a systolic thrill at the upper and mid-left sternal borders are commonly present (50%).
3. in classical type on auscultation S1 ►soft S2 ►Loud duo over flow on aorta (cause aortic
dilation and may cause AR ) In pink TOF loud S2 duo pulmonary component and pan systolic murmur .
in TOF with absent of PV ejection systolic murmur and diastolic murmur
In a deeply cyanotic neonate with TOF with pulmonary atresia, heart murmur is absent, although a continuous murmur representing PDA or collateral may be occasionally audible(Continuous machinery murmur).
An ejection click that originates in the aorta may be audible. The S2 is usually single because the pulmonary component is too soft to be heard. A long, loud (grade 3 to 5/6) ejection-type systolic murmur is heard at the middle and upper left sternal borders. This murmur originates from the PS but may be easily confused with the holo-systolic murmur of a VSD. The more severe the obstruction of the RVOT, the shorter and softer the systolic murmur.
Note
Any VSD with right to left shunt you can’t hear the murmur!
Any right to left shunt through any defect (VSD ASD PDA) has no murmur!
ELECTROCARDIOGRAPHY
1-Right axis deviation .In the acyanotic form, the QRS axis is normal.
- RVH is usually present; BVH may be seen in the acyanotic form. RAH is occasionally present
Tall R wave in V1 and 2 (due to right ventricular hypertrophy) in classical type T1 from day 0 to 7 it is positive then it will be negative till 12y of age, so if you find positive T wave between 7d and 12y think of right ventricular abnormality.
Tall R wave in V5 and 6 (due to left ventricular hypertrophy) in pink type
X-RAY STUDIES
1-The heart size is normal or smaller than normal, and pulmonary vascular markings are decreased. “Black” lung fields are seen in TOF with pulmonary atresia and right side hypertrophy and aorta prominent.. And plethoric lung (white) in pink TOF and left side hypertrophy and PA prominent.
2-A concave main PA segment with an upturned apex (i.e., “boot-shaped” heart or coeur -en -sabot) is characteristic classical type
3-right aortic arch (25%) may be present classical type. 50 -70 % in TOF with PV atresia.
NATURAL HISTORY
1-Infants with acyanotic TOF gradually become cyanotic. Patients who are already cyanotic become more cyanotic as a result of the worsening condition of the infundibular stenosis and polycythemia.
2-Polycythemia develops secondary to cyanosis.
3-Physicians need to watch for the development of relative iron-deficiency state (i.e.,hypochromia)
4-Hypoxic spells may develop in infants
5-Growth retardation may be present if cyanosis is severe.
6-Brain abscess and cerebrovascular accident rarely occur
7-SBE is occasionally a complication.
8-Some patients, particularly those with severe TOF, develop AR.
9-Coagulopathy is a late complication of a long-standing cyanosis
TOF
Hypoxic spell
Definition
How does Hypoxic spell happen?
INCREASE IN INFUNDIBULAR CONTRACTILITY
Hypoxic spell
(also called cyanotic spell, hypercyanotic spell, “tet” spell) of TOF requires immediate recognition and appropriate treatment because it can lead to serious complications of the CNS.
Hypoxic spells are characterized by a paroxysm of hyperpnea (i.e., rapid and deep respiration), irritability and prolonged crying, increasing cyanosis, and decreasing intensity of the heart murmur. Hypoxic spells occur in infants, with a peak incidence between 2 and 4 months of age.
These spells usually occur in the morning after crying, feeding, or defecation. A severe spell may lead to limpness, convulsion, cerebrovascular accident, or even death. There appears to be no relationship between the degree of cyanosis at rest and the likelihood of having hypoxic spells
How does Hypoxic spell happen?
1-Imbalance between pulmonary & systemic vascular resistance, decreased pulmonary blood flow & increased right-to-left shunting which results
2-fall of arterial PaO2
3-Fall in pH stimulate respiratory center =hyperpnoea
Presence of fixed resistance at the RVOT= more shunting which cause vicious cycle of hypoxic spell.
INCREASE IN INFUNDIBULAR CONTRACTILITY :
Hypoxemic spells are caused by spasm of the infundibulum of the right ventricle which precipitates a cycle of progressively increasing right to left shunting and metabolic acidosis.
- Hyperpnea increases oxygen demand & cardiac output
- Increases the systemic venous return leading to right to left shunt as well as oxygen consumption, Explained the occurrence of spell in early morning & during Valsalvalike maneuver (crying, bowel movement)
TOF
Management of spells
After spells
Prevention of spells
COMPLICATION OF TOF
Management of spells
- Check airway and start oxygen. If child is uncomfortable with mask or nasal cannula, deliver oxygen via tube whose end is held ½ - 1 inch away from nose. This corresponds to delivering 80% oxygen. (to increase saturation, concentration does not matter as the ductus arteriosus is already closed)
- Knee - chest position.(We do such positioning to increase systemic vascular resistance by pressing the aorta causing the blood to return and go through the lung)
- Obtain a reliable intravenous access.
- Sedate child with subcutaneous morphine 0.2 mg/kg/dose]or i/m ketamine [ 3-5 mg/kg/dose] if the access is not obtainable expeditiously.
- Soda -bicarbonate 1- 2 ml/kg
- Correct hypovolemia (10ml/kg fluid dextrose normal saline).
- Keep the child warm.
- Start beta -blockade. Beta blockade is fairly safe unless a specific contraindication like bronchial asthma or ventricular dysfunction exists. It should always be given with heart rate monitoring.
Medications and dosages:-
1- IV metoprolol 0.1 mg/kg, given slowly over 5 min and can repeat every 5-min for a maximum of 3 doses then can be followed by infusion 1-2 mcg/kg/min
2-Monitor saturation, heart rates & BP and aimed to keep heart rate below 100/min Other options
1- I/v Esmolol: Esmolol is relatively expensive but has the advantage of being very short acting.
2- I/V propranolol [0.1 mg/kg].If desaturation persists and there is still no significant trend towards improvement despite maximum beta blockage
3-Start vasopressor infusion Methoxamine Phenylepherine
4-If spells are persistent, consider paralyzing the child, elective intubation and ventilation and plan for surgery, which can be corrective or palliative [BT shunt]
5-If convulsions occur- consider IV diazepam 0.2 mg/kg or IV midazolam 0.1-0.2 mg /kg/dose, as slow push.
6-Appropriate and timely management of cyanotic spells can save lives and prevent CNS insults.
After a Spell:
1-After a spell is successfully managed, a careful neurological examination is mandatory. In case of suspicion of neurologic insult during a spell, a CT scan is to be done to assess the presence and extent of cerebral infarcts.
(Most risk factor for developed employ like stroke is polycythemia)
2-Initiate maximally tolerated beta-blockade (propranolol 0.5-1.5 mg/kg/dose 8hourly or 6 hourly). The dose can be titrated by the heart rate response.
3- Plan towards early corrective or palliative operation (depending on the age and anatomy).
4- Correct anemia by packed cell transfusion. Hemoglobin levels < 12 gm/dl merit correction through a blood transfusion in children with cyanotic spells; Continue therapeutic (if anemic) or prophylactic iron therapy (if not anemic).
Preventing a Spell in a Child with a Cyanotic Congenital Heart Defect :-
1-Parents of patients diagnosed to have a cyanotic congenital heart defect should be counseled if the possibility of occurrence of a spell is anticipated
2-Explain to them the circumstances when a spell may occur.
3-Avoid dehydration.
4-Rapid control of temperature whenever fever occurs
5-Encourage early surgical repair
COMPLICATION OF TOF
1- Stroke
2- infective endocarditis (risk site aorta and pulmonary valve)
3- brain abscess
4- anemia duo polycythemia (over use of iron ) and cause IDA .
Why do I treat patient ? duo IDA increase risk of stroke and cyanotic spell.
5- low IQ (patient with cyanosis do surgery as early as soon you will protective him
from low IQ)
BIRTH INJURIES
Definition
Risk factors
SUBGALEAL HEMORRHAGE
RUPTURED ORGANS
ADRENAL HEMORRHAGE
BIRTH INJURIES
Definition:
an impairment of infant’s body or structure due to adverse influences which occurred at birth.
-Larger babies are more liable.
-Most cases are self-limited.
Risk factors:
- Primi-parity.
- Small maternal stature.
- Prolonged labor or rapid labor.
- Oligohydramnios.
- Macrosomia.
SUBGALEAL HEMORRHAGE:
This is a rare but potentially lethal condition in the newborn baby, caused by rupture of the veins that connect between the dural sinuses and the scalp veins which leads to accumulation of blood between the epicranial aponeurosis (the galea) and the periosteum, and this can cause hypovolemic shock and death.
RUPTURED ORGANS:
e.g. liver, spleen, and adrenal glands.
All are seen due to pressure on these organs during delivery, commonly in breech presentation & large babies.
ADRENAL HEMORRHAGE:
It is common in infants of diabetic mothers. It presents as a triad of: :
-Shock.
-Abdominal mass.
-Cyanosis.
Treatment: supportive, surgical repair, treatment of adrenal failure by liberal fluid and corticosteroids replacement.
ERBS PALSY (vs.) KLUMPKE’S PALSY
ERBS PALSY:
-It is due to traction of C5,C6 nerve roots.
-The limb is held limply on the side of the body with the forearm pronated (waiter tip position).
-Grasp reflex is present.
-Recovery in >80% of cases.
-Physical therapy should be started by 7-10 days.
KLUMPKE’S PALSY:
-C7,C8,T1 nerve roots are involved.
-The small muscles of the hand and wrist are affected.
-Loss of sweating and sensation may also be seen.
-Grasp reflex is absent.
-It carries bad prognosis.
FRACTURE OF THE CLAVICLE (vs.) STERNOCLEIDOMASTOID TUMOR (MASS)
FRACTURE OF THE CLAVICLE:
-It is the most common bone injury during birth.
-It can be asymptomatic, or features of fracture, or pseudoparalysis.
-A callus is formed at 7-10 days.
-Treatment: Analgesics, and pinn the sleeve to the shirt of infant.
-Complete recovery is expected.
STERNOCLEIDOMASTOID TUMOR (MASS):
- 1-2 cm mass.
-Appears at 2-3 weeks.
-Usually unilateral.
-80% recover in 3-4 months by physiotherapy.
-Plastic surgery is needed if it persists for>6months.
CEPHALHEMATOMA (vs.) CAPUT SUCCEDANEUM
CEPHALHEMATOMA:
-It is a localized tense mass due to sub-periosteal hemorrhage.
underlie cephalhematoma (<20%).
-Common site is the parietal bones.
-It is limited by the suture lines.
-It may cause anemia and jaundice.
-Linear skull fractures may
-Resolution occurs over weeks ending with calcification.
-NO TREATMENT is required.
-Aspiration should never be done.
-Brain CT scan is done only if neurological manifestations are present.
CAPUT SUCCEDANEUM:
-Is a diffuse soft mass due to subcutaneous collection of fluid.
-It has poorly defined margins.
-It crosses the midline and sutures.
-It resolves spontaneously over few days. –No complications.
NEONATAL POLYCYTHEMIA
NEONATAL POLYCYTHEMIA:
It is defined as venous PCV more than 65% (capillary PCV is 15% higher than venous PCV).
ETIOLOGY:
1.Increased intrauterine erythropoiesis e.g. IUGR, post-date, trisomies.
2.Secondary to RBC transfusion e.g. delayed cord clamping(>3min.), twin to twin transfusion.
3.Increased capillary permeability & plasma loss e.g. prematurity, hypoxia, cold stress. CLINICAL FEATURES:
● Commonly asymptomatic(only plethoric).
● Symptoms(are related to increased blood viscosity and decreased organs perfusion):
lethargy, irritability, poor feeding, hypoglycemia, convulsions, N.E.C., peripheral gangrene, renal vein thrombosis. TREATMENT:
If venous PCV is >65% and no symptoms: observation.
If PCV is >70% or >65% with symptoms:
do partial exchange transfusion with normal saline aiming a desired PCV of less than 55%.
Volume of exchange(ml)=
blood volume x (observed PCV - desired PCV ) /observed PCV.
(Blood volume: in term infants=80-90 ml/kg in preterm=90-100ml/kg).
NEONATAL CONVULSIONS
NEONATAL CONVULSIONS:
Convulsion is defined as paroxysmal alteration of neurologic function, including behavioral, motor and /or autonomic changes.
Neonates have higher risk of convulsions because of immaturity of the brain.
80% of cases present in the first 48 hours of life, and it can lead to serious complications e.g. feeding difficulties, C.P., and epilepsy (in 50% of cases). TYPES OF NEONATAL CONVULSIONS:
● 1. Focal: is the commonest type.
● 2. Multi-focal: many muscle groups are involved. 3.Tonic: rigid presentation with deviation of eyes. It has poor prognosis.
● 4. Myoclonic: brief focal or generalized jerks of the extremities or body (usually associated with severe brain damage).
- Subtle seizures: e.g. chewing, blinking, apnea, cyanosis, or nystagmus. It is the most common type of seizures following H.I.E. ●
Any abnormal movement in the neonate is regarded as fit till proved otherwise & it should be distinguished from normal behaviors in neonates such as:
- Stretching.
- Spontaneous sucking.
● - Random, non-specific movements of limbs.
● - Benign myoclonus which may occur during rapid eye movement sleep.
- Breath holding.
● - Jitteriness ( which is stimulus- dependent , not accompanied by abnormal eye movements & stopped by gripping the limb).
● CAUSES OF NEONATAL CONVULSIONS:
● 1. Hypoglycemia.
● 2. Hypocalcemia , hypomagnesemia.
● 3. Hypo / Hypernatremia.
● 4. Meningitis.
● 5. Intracranial bleeding.
- Perinatal asphyxia.
- Bilirubin encephalopathy. 8. Pyridoxine dependency ( a rare A.R.
disorder). Rx by large dose of B6 (100-200 mg i.v.).
- Cerebral malformations.
10.Inborn errors of metabolism.
- Drug withdrawal. e.g.Diazepam.
- Benign familial neonatal seizures (A.D.).
- Benign idiopathic neonatal seizures (fifth day fits) diagnosed by exclusion.
- No cause is found (in 10% of cases).
. LAB. STUDIES:
● 1. Blood sugar & electrolytes.
● 2. CSF analysis: should be considered in all cases as seizures may be the first sign of neonatal meningitis.
- E.E.G.
- Brain ultrasound, CT, MRI.
- Serum & urine chromatography.
●
● TREATMENT:
- Stabilize vital functions.
● a.Diazepam (0.3mg/kg iv or 0.5mg/kg rectally), Lorazepam (0.05mg/kg iv), Medozolam. b.Phenobarbital 20mg/kg loading dose (can be repeated after 10min.) then 5mg/kg/day in 2 divided doses.
- Stop convulsion by:
● c.Phenytoin (doses similar to phenobarb.).
● e.Sodium valproate (iv or rectal).
●3.Treat the underlying cause & correct metabolic abnormalities. DURATION OF TREATMENT:
●
If convulsions are resolved, if neurological findings are normal, & if EEG is normal, anticonvulsants can be stopped within the first 14 days of life, otherwise it should be continued for 1-3 months.
The main factor which determine the outcome is the underlying cause & not the seizure itself.
Neonatal hypoglycaemia
Definition
Physiology
Cf
Causes
Ttt
Neonatal hypoglycaemia (vs.) NEONATAL HYPOCALCEMIA
It is defined as blood glucose level <1.4mmol/L(25mg/dl)in the first 24 hours of life and< 2mmol/L(40mg/dl) thereafter.
90% of glucoseis consumed by the brain.
Blood glucose is maintained by:
- Adequate fetal glycogen stores.
- Effective glycogenolysis and gluconeogenesis.
- Good intake.
Clinical Features:
Tachycardia, jitteriness, lethargy, poor feeding, apnea, cyanosis, seizure. Some cases are asymptomatic & treated by early feeding.
Causes of Neonatal Hypoglycemia:
- I.U.G.R.
- Prematurity.
- Birth asphyxia.
- Neonatal sepsis.
- Delayed or poor feeding.
- IDM(infants of diabetic mothers).
TREATMENT OF HYPOGLYCEMIA:
10%Dextrose i.v.as 4ml/kg stat, then 8mg/kg/minute is given if blood glucose is <25mg/dl.
If blood glucose remains low for more than 7days (persistent hypoglycemia): increase the dose of dextrose to 16-20mg/kg/minute, and investigate for causes e.g. hyperinsulinism & inborn error of metabolism.
NEONATAL HYPOCALCEMIA:
Calcium is present in three forms:
- Protein bound (40%).
- Bound to citrate or phosphate (10%).
- Ionized: which is the active part (50%).
Hypocalcemia is defined as:
serum calcium < 2 mmol/L (8 mgdL) in term, or less than 1.75 mmol/L (7 mg/dL) in preterm neonates, or ionized calcium < 4mgdL Acidosis results in an increased ionized calcium and alkalosis decreases it.
SCREENING FOR HYPOCALCEMIA IS ROUTINELY INDICATED IN:
- Preterm neonates.
2.I.D.M.
- Severe perinatal asphyxia.
CLINICAL FEATURES:
range from asymptomatic to jitteriness, tremor of the extremities, tetany, cardiac arrhythmias, convulsions, apnea, and stridor.
TYPES OF NEONATAL HYPOCALCEMIA:
- Early:
which presents within the first 72 hours, due to poor feeding e.g. in RDS, preterm, sepsis.
- Late
which presents at 5-7days up to several weeks,due to transient hypoparathyroidism, or high phosphorus content in milk.
TREATMENT:
If convulsions are present give 10% calcium gluconate 100-200mg/kg by i.v. infusion (0.2-0.5ml/kg) for three days.
Always watch for extravasation & tissuing of calcium which may cause skin necrosis. Oral vit.D 5000 1.U./day should also be given.
INFANTS OF DIABETIC MOTHERS (IDM)
INFANTS OF DIABETIC MOTHERS (IDM):
Infants born to type 1 or 2 or gestational diabetic mothers have higher mortality rates, and most of them are L.G.A., but they may be growth restricted if DM is complicated by vascular disease or if they are delivered before term.
PATHOHPYSIOLOGY:
Maternal hyperglycemia causes fetal hyperglycemia and fetal hyperinsulinemia. The resultant fetal increased hepatic glucose intake and lipogenesis causes hypertrophy and hyperplasia of pancreatic islet cells and all fetal organs (except the brain), and extramedullary hematopoiesis. Separation of the placenta at birth suddenly interrupts glucose infusion to the neonate, and hypoglycemia develops in the first few hours after birth.
CLINICAL MANIFESTATIONS:
Most IDM are large and plump (due to increased body fat and enlarged viscera). They have higher risk for birth trauma and congenital anomalies, with puffy, plethoric facies. Hypoglycemia develops in 25-50% of IDM, but only a small percent of them become symptomatic in the first 3 days of life; similar signs can be due to hypocalcemia and asphyxia.
IDM have a higher incidence of T.T.N., R.D.S., N.N.J., hypothermia, polycythemia, and renal vein thrombosis.
Congenital heart disease, asymmetrical septal hypertrophy, cardiomegaly, and heart failure are more common in IDM. TREATMENT OF IDM:
1.Good glycemic control before and during pregnancy can reduce mortality and complications of IDM.
2.IDM should start feedings within 1 hr. after birth with close observation.
3.Treatment is indicated if the infant is symptomatic and plasma glucose < 40mg/dl, or asymptomatic and plasma glucose is < 30mg/dl.
4.Treatment of RDS, hypocalcemia, hypomagnesemia, and polycythemia.
PROGNOSIS OF I.D.M.:
•They have a higher incidence of subsequent DM and childhood obesity that may extend to adult life.
NEONATAL ASPIRATION PNEUMONIAS
NEONATAL ASPIRATION PNEUMONIAS
- MECONIUM ASPIRATION:
Meconium-stained amniotic fluid is found in 10-15% of births (usually term or postterm),following fetal distress & hypoxia.
5% of such infants develop meconiumaspiration pneumonia when thick meconium is aspirated into the lungs while in utero or with the first breath. 1. Plugging of small airways with hyperinflatio TREATMENT:
- Supportive care and physiotherapy.
- I.P.P.V.
- Surfactant therapy.
- Inhaled nitrous oxide (iNO).
- E.C.M.O.(extracorporeal membrane oxygenation).
- Pulmonary hypertension may follow, and a non selective pulmonary vessel alpha blocker tolazoline is used.
- Antibiotics.
- Pneumothorax occurs in 15% of cases, it should be treated accordingly. 2. MILK ASPIRATION:
Commonly occurs in preterm infants, or in full term infants with improper feeding technique. It is characterized by sudden deterioration in clinical condition (apnea or severe distress).
CXR shows pneumonic patch or collapse usually involving the right upper lobe.
TREATMENT:
Supportive care.
Normal lung function required
TTN( definition,predisposing factor,cxr,Mgx)
Neonatal RDS
Definition and risk factors
THE INCIDENCE OF R.D.S. IS DECREASED WITH
SURFACTANT DEFICIENCY LEADS TO
NATURAL HISTORY OF RDS
CLINICAL PRESENTATION OF R.D.S.
Cxr
PREVENTION OF R.D.S
ANTENATAL STEROIDS
SURFACTANT REPLACEMENT
TYPES OF SURFACTANT
COMPLICATIONS OF SURFACTANT
TREATMENT OF R.D.S. (IN THE N.I.C.U.)
CAUSES OF SUDDEN DETERIORATION OF R.D.S. WHILE ON SPONTANEOUS BREATHING:
COMPLICATIONS OF R.D.S
B.P.D( definition & cxr)
NORMAL LUNG FUNCTION REQUIRES:
1.Clearance of fetal lung fluid.
2.Establishment of spontaneous breathing.
3.Release of surfactant.
4.Decreasein pulmonary vascular resistance.
5.Cessation of right to left shunting of venous blood returning to the heart.
Interference with any of these mechanisms will result in respiratory distress in the neonate.
T.T.N. and R.ID.S. are the commonest causes for respiratory distress in neonates at all.
TRANSIENT TACHYPNEA OF THE NEWBOMF (T.T.N.)
Is defined as tachypnea of a newborn(commonly affects term babies) without prominent respiratory distress signs, occurring shortly after birth, due to delayed resorption of lung fluid, with rapid resolution by 24-72 hours in most cases.
PREDISPOSING FACTORS OF T.T.N.:
- C.S.
- Perinatal asphyxia.
- Hypothermia.
- Maternal DM and asthma.
- Large baby.
C.X.R.:
a. Hyperinflation.
b. Peri-hilar opacities.
c. Fluid in the transverse fissure (appears as
white streaks in lung fissures which disappears within few days)
MANAGEMENT
• Oxygen for 2-3 days, concentration more than 40% is rarely needed.
• Antibiotics, since it initially may simulate G.B.S. pneumonia.
• Diuretics are not useful.
RESPIRATORY DISTRESS SYNDROME (R.D.S) :
Preterm infants have pulmonary immaturity which results in surfactant deficiency. Surfactant (produced by type 2 pneumocytes) is a complex mixture of phospholipids, proteins, And lipids that lowers the surface tension of the alveolar membrane. Without surfactant the alveoli w ill collapse at the end of each expiration? and this can lead to K.D.S. and respiratory failure in the neonate.
The risk of R.D.S. is inversely correlated with gestational age. Nearly all infants born before 28 weeks of pregnancy develop R.D.S.
RISK FACTORS FOR R.D.S. INCLUDE:
- Previous sibling with R.D.S.
- Maternal D.M.
- Cesarean section(C.S.).
- Rapid labor.
- Multiple pregnancy.
THE INCIDENCE OF R.D.S. IS DECREASED WITH:
- Use of antenatal steroids.
- Maternal hypertension.
- Prolonged rupture of membranes.
The synthesis of surfactant requires normal temperature, normal PH, and normal lung perfusion.
Phosphatidyl choline (Lecithin) is the major constituent of the mature surfactant. Lecithin to sphyngomyelin (L/S) ratio (measured in a sample of amniotic fluid collected via amniocentesis) is a standard test to confirm R.D.S.
Lecithin and sphyngomyelin are phospholipids found in the amniotic fluid.
As the lung matures and begins to produce surfactant; Lecithin levels will increase, while sphingomyelin level remains constant.
L/S ratio of 2.0 or greater indicates that R.D.S. is unlikely because there is enough surfactant.
SURFACTANT DEFICIENCY LEADS TO:
a. Alveolar collapse and hypoventilation with CO2 retention.
b. Reduced lung volume and compliance with increased dead space.
c. Ventilation / perfusion mismatch.
d. Pulmonary hypertension.
e. Right to left (R-L) shunt.
NATURAL HISTORY OF RDS:
It appears immediately or within the first 4 hours after birth, then it worsens for the next 48-72 hours.
Clinical recovery coincides with the onset of diuresis after a period of oliguria, and resolution occurs 2-4 days later, but some neonates may remain O2 dependent for several weeks.
CLINICAL PRESENTATION OF R.D.S.:
- Tachypnea (respiratory rate > 60/min.).
- Grunting.
- Sternal, intercostal, and subcostal retractions.
- Cyanosis in room air.
- Oliguria.
- Mixed respiratory and metabolic acidosis.
Grunting: is a short, low pitched sound heard when the infant expires with a partially closed glottis.
It can conserve lung volume and keep the alveoli opened. Grunting indicates a parenchymal disease and poor lung compliance.
C.X.R. :
Typical findings appear at 6-12 hr.:
- Diffuse bilateral reticulo-granular infiltrates (ground glass appearance) with small lung volume and a bell-shaped thorax.
- Air bronchogram .
- In severe cases there is complete white-out of lung fields.
Air bronchogram refers to the phenomenon of air-filled bronchi (dark) being made visible by the opacification of surrounding alveoli (grey/white). It is almost always caused by a pathologic airspace/alveolar process, in which something other than air fills the alveoli. Air bronchograms will not be visible if the bronchi themselves are opacified (e.g. by fluid) and thus indicate patent proximal airways.
PREVENTION OF R.D.S.:
a. Good antenatal care.
b. Good selection and timing of C.S. (avoid doing elective C.S. for low risk fetuses before 39 wk. of gestation, because surfactant secretion generally increases during labor).
c. Antenatal steroid.
d. Surfactant replacement (surfactant can be used as prophylaxis and as rescue treatment for R.D.S.).
ANTENATAL STEROIDS:
When given to mothers suspected to get preterm delivery (at 24-34 wk.) 1-2 days before delivery can induce fetal surfactant production.
Betamethasone (2 i.m. doses) is superior to Dexamethasone (4 i.m. or i.v. doses) which can cause periventricular leukomalacia in the newborn baby.
SURFACTANT REPLACEMENT :
Given within 20-30 minutes after birth by trained physicians in qualified centers (3-4 ml/kg as 2 doses 12 hours apart) via endotracheal tube.
Surfactant reduces the incidence and severity of major complications of prematurity (R.D.S., I.V.H., N.E.C., P.D.A., B.P.D.), and also reduces the need for MECHANICAL VENTILATION & NEONATAL MORTALITY.
TYPES OF SURFACTANT:
a. Natural (bovine or porcine) is preferred.
b. Synthetic.
COMPLICATIONS OF SURFACTANT:
- Blockage of endotracheal tube.
- Hypoxia(transient).
3.Hypotension.
TREATMENT OF R.D.S. (IN THE N.I.C.U.):
a. Maintain temp. at 36.5-37.5 at all times.
b. Correct hypoxia by O2 ( 85-93% ) or assisted ventilation.
c. Correct acid - base abnormalities .
d. Nutrition (20ml/kg/day of breast milk), T.P.N.
e. Antibiotic (Ampicillin & Gentamicin) because it is difficult to differentiate R.D.S. from G.B.S. pneumonia.
f. Inhaled nitrous oxide which improves gas exchange.
g. i.v. fluid (10%dextrose)70ml/Kg/day.
h. Management of P.D.A.
Causes of sudden deterioration of r.d.s. while on spontaneous breathing:
- Pneumothorax.
- Periventricular hemorrhage.
- Aspiration.
- Apnea.
- Infection.
COMPLICATIONS OF R.D.S.:
- Air leak .
- P.D.A .
- Periventricular hemorrhage .
- Pneumonia .
- Complications of mechanical ventilation.
- Long term sequelae e.g. R.O.P. & B.P.D. (which occur in severe cases of R.D.S. which require assisted ventilation for > 4 weeks).
BRONCHOPULMONARY DYSPLASIA
Chronic respiratory distress following prolonged exposure (>28 days) to high pressure LP.P.V. causing repeated over- distension of the alveoli & alveolar ducts in neonates with pulmonary insufficiency (usually preterm).
CXR in B.P.D. shows massive destruction of lung tissues, with areas of collapse, atelactasis, and cystic
NEONATAL APNEA
NEONATAL APNEA:
• Definition:
• Cessation of breathing for > 20 seconds, or for any duration if associated with bradycardia or cyanosis.
• Periodic breathing :
• Series of respiratory pauses of 10 seconds occuring at least 3 times/minute, followed by a series of rapid, shallow breaths without bradycardia or cyanosis. It is common in premature neonates. TYPES OF APNEA:
• Central : due to cessation of motor stimuli from the brain stem. Chest wall motions are absent.
• Obstructive : absence of airflow, with aggressive chest wall motion.
• Mixed : is the commonest type. CAUSES OF APNEA:
• Hypoxia.
• Sepsis.
• Metabolic disorders.
• CNS disorders.
• Circulatory e.g. hypotension, heart failure, anemia, polycythemia.
• Hyperthermia, Hypothermia.
• Excessive pharyngeal suctioning.
• Over dose of anticonvulsants e.g. Diazepam, Phenobarbiton.
• Apnea of prematurity.
So the diagnosis of apnea requires investigations of the above causes by appropriate tests. • 1. Apnea monitors.
TREATMENT :
• 2. Repeated stimulation.
• 3. Intermittent bag&mask.
• 4. C.P.A.P.(CONTINOUS POSITIVE AIRWAYS
PRESSURE)VENTILATION is useful in cases
of
obstructive and mixed apnea, but not useful in central apnea. • 5. Drugs e.g. Theophylline (5-7mg/kg loading, then 12mg/kg/6-12hr.oral or i.v.) It is useful in all types of apnea. It sensitizes the respiratory centers to hypercapnia & it stimulates the diaphragm, but it decreases cerebral blood flow.
• Other drugs e.g. Caffaine citrate and Doxapram. APNEA OF PREMATURITY:
• Immaturity of respiratory centers or chemoreceptors in premature babies may cause irregular stimulation of breathing and recurrent apnea.
CENTRAL RECEPTORS respond to hypercapnia and acidosis.
CHEMORECEPTORS (carotid and aortic bodies) respond to hypoxia.
PERINATAL ASPHYXIA
PERINATAL ASPHYXIA:
Perinatal asphyxia occurs when antepartum, intrapartum, neonatal, or a combination of these events result in hypoxia and ischemia of the brain (the so-called hypoxic- ischemic encephalopathy) and other organs. HYPOXIC-ISCHEMIC ENCEPHALOPATHY(H.I.E.):
Hypoxia means decreased arterial concentration of oxygen. Ischemia means blood flow to cells or organs that is insufficient to maintain their function.
H.I.E. is an important cause of permanent damage to C.N.S. tissues that may result in neonatal death, or manifest later as cerebral palsy (C.P.) or developmental delay. CRITERIA OF PERINATAL ASPHYXIA:
- Umbilical cord arterial PH < 7.
- APGAR score of 0-3 for > 5 minutes.
- Neonatal neurological
manifestations (convulsions, coma, hypotonia).
- Multisystem organ dysfunction. RISK FACTORS IN THE NEONATE FOR H.I.E. :
- Very low APGAR score.
- Acidotic infants.
- Those who require C.P.R.
(cardiopulmonary resuscitation).
APGAR score is done at 1 minute after birth.
It consists of 5 criteria, each one of these criteria is graded as zero, 1, or 2 with a total score of 10
RISK FACTORS IN THE MOTHER FOR H.I.E.:
Before delivery : eclampsia, uterine infections, bleeding, severe anemia.
During labor : premature labor or prolonged labor, malpresentation, general anesthesia(G.A.). CAUSES OF LOW APGAR SCORE:
- Fetal asphyxia.
- Maternal G.A. or sedation with morphine or pethidine within the last 4 hours before delivery.
- L.B.W. & prematurity.
- Difficult or traumatic delivery. RESULTS and INTERVENTIONS at 1 min. SCORE:
7or > 7 (normal) : No resuscitation.
5-6 (moderate asphyxia) : Bag and mask. 4 or < 4 (severe asphyxia) : Endotracheal intubation and assisted ventilation.
Low score should be repeated at 5 ACUTE SEQUALAE OF ASPHYXIA :
- Cerebral hypoxia.
- Convulsions.
- I.V.H.
- Renal failure.
- Anoxic cardiomyopathy.
6.N.E.C.
7.Metabolic(hypoglycemia, hypocalcemia, inappropriate A.D.H. secretion).
LONG-TERM OUTCOMES AFTER H.I.E. :
- Cognition and developmental delay.
- Learning difficulties.
- Cerebral palsy.
- Vision defects.
- Epilepsy.
- Hearing loss.
TREATMENT OF PERINATAL ASPHYXIA:
1.Treatment of cerebral edema:
a. Correct hypoxia & acidosis.
b. Control convulsions (in 20-50% of HIE cases).
c. Restrict i.v. fluid to 60 ml/kg/day.
d. Mannitol 5 ml/kg/dose over 20 minutes, can be repeated 4 times a day.
e. Dexamethason 1 mg loading dose then
0.3 mg/kg 8 hourly for 3 days.
f. Hyperventilation.
2. Maintain normal cerebral tissue perfusion e.g.by giving blood to prevent neuronal damage.
- Maintain renal function
Torch
TOXOPLASMOSIS
TOXOPLASMOSIS:
Toxoplasma gondii is an obligate intracellular parasite that can infect humans through the feces of its primary host which is the cat.
Congenital toxoplasmosis results from vertical (transplacental) transmission of the parasite from an acutely infected mother to her fetus.
If infection occurs early in pregnancy, there is low rate of transmission, but it causes severe disease, while infection late in pregnancy causes high transmission, but more benign symptoms. Clinical features:
The classic findings of S.G.A., microcephaly, hydrocephalus, chorio-retinitis, and intra-cerebral calcifications.
Jaundice, hepatosplenomegaly(HSM). Generalized maculopapular rash.
Seizures.
Long-term neurologic & developmental complications. Diagnosis:
IgG-specific antibodies achieve a peak concentration 1-2 months after infection and remain positive indefinitely.
Specific IgM antibody determinations should be performed to confirm disease.
Treatment:
Pyrimethamine (supplemented with folic acid) combined with Sulfadiazine should be given both for symptomatic and asymptomatic congenital infections for up to 1 year.
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Rubella
RUBELLA:
If infection is acquired during the first 4 weeks of gestation; most newborns will have congenital defects.
Infection acquired after 4 months’ gestation does not seem to cause disease. Clinical features:
Classical triad of cataract, cardiac defects(PDA), and deafness (sensorineural).
Meningoencephalitis, Mental retardation.
Jaundice, HSM, post auricular lymphadenopathy. Thrombocytopenia.
Radiolucent bone disease.
Purpuric skin lesions “blueberry muffin” appearance resulting from extramedullary (dermal) erythropoiesis. Diagnosis:
-Detection of rubella-specific IgM antibody in the infant usually indicates recent infection.
-Rubella virus can be isolated from blood, urine, CSF, and throat swab specimens.
-Infants should be isolated while in hospital, and kept away from susceptible pregnant women when sent home.
-No treatment is available for congenital rubella syndrome.
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CMV
CYTOMEGALOVIRUS:
CMV is the most common congenital infection, and is the leading cause of sensorineural hearing loss, mental retardation, retinal disease, and cerebral palsy.
The earlier in gestation that the primary maternal infection occurs, the more symptomatic the infant will be at birth.
CMV infection acquired during birth or from mother’s milk is not associated with newborn illness or CNS sequelae. Clinical features:
Microcephaly.
Thrombocytopenia.
HSM.
Chorio-retinitis.
Hearing abnormalities.
A blueberry muffin appearance as the result of dermal erythropoiesis.
Skull films may reveal periventricular calcifications. Diagnosis:
-Detection of the virus in urine or saliva of the infant.
-PCR can detect small amounts of CMV DNA in urine.
-Detection of CMV within the first 3 weeks after birth is considered as a proof of congenital CMV infection. Treatment:
-No antiviral agents currently approved for the treatment of congenital CMV infection.
-Ganciclovir and Valganciclovir can only delay the progression of hearing loss.
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HSV
HERPES SIMPLEX VIRUS:
HSV type 2 is responsible for most cases of primary (maternal) genital herpes & neonatal herpes simplex infection.
Neonatal infection is acquired from the mother shortly before or during passage through the birth canal at delivery.
Infants with HSV infections are more likely to be born prematurely. Clinical features
Most infants are normal at birth, and symptoms of infection develop at 5-10 days of life either as:
disseminated disease involving multiple organ systems, especially the liver and lungs, or as localized infection to the CNS, skin, eyes, and mouth. HSV infection should be suspected in any neonate with fever, irritability, seizures, and abnormal CSF findings.
HSV infections are often severe, and a delay in treatment results in significant morbidity & mortality. Diagnosis:
- Specimens for viral culture (blood, urine, saliva).
- PCR is a sensitive method for detecting HSV DNA in blood, urine, and CSF. Treatment:
Parenteral Acyclovir is the treatment of choice for neonatal HSV infections.
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CONGENITAL SYPHILIS
CONGENITAL SYPHILIS:
It commonly results from transplacental infection with the Gram negative spirochet Treponema pallidum to the fetus. Syphilis during pregnancy has about 100% transmission rate. -Intrauterine infection can result in stillbirth, non immune hydrops fetalis, or prematurity.
-Early manifestations:
-Snuffles (syphilitic rhinitis) is the first symptom seen in up to 50% of newborns with congenital syphilis.
-HSM, LAP.
-Severe pneumonia and osteochondritis.
-A maculopapular desequamative rash develops over the palms and soles and around the mouth and anus.
-Hemolytic anemia and thrombocytopenia. -Late manifestations:
-Interstitial keratitis. -Deafness.
-Frontal bossing. -Saddle nose.
-Hutchinson teeth (triangular or peg like appearance of the incisors and molars).
-Mulberry molars (physically defective permanent molars).
-Bowing of the shins.
-Clutton joints (symmetrical hydrarthrosis of knee joints). TREATMENT:
Parenteral penicillin G (for 10 to 14 days) is the drug of choice for treatment of syphilis.
Autosomal Dominant Inheritance
Autosomal Dominant Inheritance
- is determined by the presence of 1 abnormal gene on 1 of the autosomes (chromosomes 1-22).
- In an autosomal dominant trait, a change in 1 of the paired genes has an effect on the phenotype.
- The disorder is transmitted in a vertical (parent-to-child) pattern and can appear in multiple generations.
- An affected individual has a 50% (1 in 2) chance of passing on the deleterious gene in each pregnancy and, therefore, of having a child affected by the disorder. This is referred to as the recurrence risk for the disorder.
- Unaffected individuals (family members who do not manifest the trait) do not pass the disorder to their children.
- Males and females are equally affected. - Although parent-to-child transmission is a characteristic of autosomal dominant inheritance, for many patients with an autosomal dominant disorder there is no history of an affected family member. There are several possible reasons:
- New mutation
- Incomplete penetrance, meaning that not all individuals who carry the mutation have phenotypic manifestations.
- Variable expression: Individuals with the same autosomal dominant mutation can manifest the disorder to different degrees.
- Somatic mutations: Some spontaneous genetic mutations occur not in the egg or sperm that forms a child, but rather in a cell in the developing embryo.
5 . Germline mosaicism: the mutation occurs in cells that populate the germline that produce eggs or sperm.
Examples of AD disease: achondroplasia, hereditary spherocytosis, neurofibromatosis, Marfan syndrome, and osteogenesis imperfecta.
Autosomal Recessive Inheritance
Autosomal Recessive Inheritance
- Horizontal transmission, the observation of multiple affected members of a kindred in the same generation, but no affected family members in other generations.
- Recurrence risk of 25% for parents with a previous affected child.
- Males and females being equally affected.
- The affected individual should be homozygous for the affected gene.
- If both parents are heterozygous the chance of having affected child is 25%.
- If the affected person married from normal person, all the children will be heterozygous. - If affected person married from a heterozygous person the children will be: 50% affected. It is called Pseudodominant inheritance, which refers to the observation of apparent dominant (parent to child) transmission of a known AR disorder.
50% heterozygous (carrier).
Examples of AR disease: Sickle cell disease, PKU, Tay-sachs disease, Cystic Fibrosis, Hurler Disease, Werdnig-Hoffmann Disease, Alkaptonuria, Albinism, and Congenital adrenal hyperplasia.
X-Linked Recessive Inheritance
X-Linked Recessive Inheritance
◆ Males are more commonly and more severely affected than females.
◆ Female carriers are generally unaffected.
◆ Female carriers have a 25% risk for having an affected son, a 25% risk for a carrier daughter, and a 50% chance of having a child that does not inherit the mutated X-linked gene.
◆ Affected males have carrier daughters and unaffected sons because they pass their X chromosome to all of their daughters Y chromosome to all of their sons. ◆ A female occasionally exhibits signs of an X-linked trait similarly to a male. This occurs rarely owing to:
- homozygosity for an X-linked trait.
- the presence of a sex chromosome abnormality (45X0).
- nonrandom X-inactivation.
Examples of X-linked recessive diseases: Hemophilia A and B, Lesch Nyhan Syndrome, Hunter`s syndrome D.M.D., G6PD, and Color-blindness.
X-Linked Dominant Inheritance
X-Linked Dominant Inheritance:
+ Female carriers typically manifest abnormal findings.
+ An affected man will have only affected daughters and unaffected sons.
+ Half of the offspring of an affected woman will be affected. + Some X-linked dominant conditions are lethal in a high percentageof males.
Examples of X-linked dominant diseases: Incontinentia pigmenti, and vit.D resistant rickets.
Multifactorial and Polygenic Inheritance
Multifactorial and Polygenic Inheritance
◆ There is a similar rate of recurrence among all 1st-degree relatives (parents, siblings, offspring of the affected child).
◆ The risk of recurrence is related to the incidence of the disease.
◆ Some disorders have a sex predilection, as indicated by an unequal male : female incidence. Pyloric stenosis, for example, is more common in males, whereas congenital dislocation of the hips is more common in females. ◆ The risk of recurrence is increased when multiple family members are affected.
◆ The risk of recurrence may be greater when the disorder is more severe.
Examples include pyloric stenosis, neural tube defects, congenital heart defects, diabetes, and cleft lip and cleft palate.
