Congenital Heart defects associated with Down syndrome: Application of Cincinnati –Ohio Program for Children’s Down - syndrome: A study for three years at Pediatric Intensive Care Unit after Open Heart surgeries and The Cardiology Out-patient Clinic of The National Institute for Heart Cairo.

Authors

*Dr.Olfat. A.El-Shafiey

Assistant Professor of Critical Care Nursing. Faculty of Nursing. Assiut University.Egypt

**Prof.Dr.William L.Cotten

Professor of Cognitive Disabilities and Congenital Heart defects. Cincinnati Children Hospital. Medical Center.Cincinnate Children’s Down syndrome Program.Cincinnati, Ohio.USA

Abstract

           A congenital anomaly is an abnormality of structure, function, or body metabolism that is present at birth and results in physical or mental disability. The incidence of congenital heart disease in children with Down syndrome is up to 75%

   The types of heart defects in children with Down syndrome can be broken down into three broad categories:1-Atrioventricular septal defects.2-Ventricular septal defect ,atrial defect or patent ducts arteriosus.3-Other complex heart disease.

    Congenital malformations of the heart are the most common of all birth defects congenital heart defect occurs when the heart or blood vessels near the heart don’t develop normally before birth. Heart defects begin in the early part of pregnancy Aims of the study are to:1- Apply Cincinnati Children’s Down syndrome program care for Dawn syndrome at coronary care unit after surgical repairs and outpatient clinic of cardiology at The National Institute for Heart  the patient and his or her parents. 2- Follow-up of the patient’s condition at the Coronary Care Unit and Coronary outpatient clinic, after one month for the prevention of complications.3-Evaluation of the individual respondents (perception) of the family.4-Assess the levels of functional independence in children with congenital heart defects before and after surgical repairs. The sampling size: 93child with Dawn syndrome and congenital anomalies of the heart their ages ranged between (2-12) years, for repair of heart defects. The following tools were applied immediately after admission, and then after one month .1-The WeeFIM (Functional Independence Measure).2-Cincinnati Children’s Down syndrome program-(Immediate Post-operative Care and Home Care after Heart Surgery).3-Self-Care Program for Dawn syndrome Children. The study revealed that there were an improvements with highly significant difference as regard physical, psychological condition of the patients and cooperation, an excellent interest from the parents for the participation in the program before and after surgeries. Congenital Heart Defects with Down syndrome Children are in need for Cardiology nurse specialist, Critical Care nurse specialist, physical therapist, anesthetist and psychologist for applying Cincinnati Children’s Down syndrome program.

Introduction

      Congenital malformations of the heart are the most common of all birth defects,  congenital heart defects can affect normally different parts or functions of the heart, although 40 to 60% of babies with Down syndrome are born with some type of cardiac abnormalities, most receive surgical correction within the first few years of life; however, an abnormality large percentage was develop Mitral Valve Prolapse (MVP) by adulthood. (1).Which the most common congenital heart disease is ventricular septal defects, ventricular septal defect is very close to the tricuspid valve which may be damaged which may lead to aortic regurgitation, aortic stenosis, aortic insufficiency, pulmonary stenosis, and hyperemia.(2).Sixty-nine percent of all Aerial Ventricular Septal defects have Down syndrome, Echocardiography or cardiac catheterization established the cardiac diagnoses ,phrenic nerve dysfunction, airway problem, pulmonary vascular hypertension, and pleural effusion (3). Pleural effusion is consider as a most serious pulmonary complications, cardiorespiratory stability was continuously monitored in all patients, and supplemental oxygen was administered as necessary.(4). If the patient requiring ventilatory assistance it is important to auscultate both lung and epigastrium, intubation route, sedation given, arterial blood gases, pulse oximetry, end-tidal CO2, lung sounds, vital signs, level of consciousness, secretions (presence, amount, color), peak inspiratory pressures, exhaled tidal volumes, and if the patient was in need for suctioning, it is important to monitor the respiratory rate, pattern, breath sounds, presence of cough, airway pressure, and oxygen saturation(5).  At the immediate post-operative period, patient may suffer from deceased cardiac output related to hypovolemia associated with surgical blood loss and persistent bleeding post-operatively; excessive loss of fluids resulting from nasogastric tube drainage, vomiting, and diuretic therapy associated with decreased fluid intake, medication therapy (e.ganesthetic, narcotics), rapid body warming following surgery and implement measures to maintain adequate cardiac output by performing actions to reduce cardiac workload .(6). For evaluating hydration status for the child after open-heart surgery, it is important to measure hematocrit, serum sodium, pulmonary capillary wedge pressure, intake, output, skin turgor. (7). Monitor for potential signs of infection because infection after open heart surgery causes a potential hazards upon the physiological functions of the heart as well as monitoring the adequacy of nutritional support reflecting the patient’s stability after operation, maintaining homeostasis within the body after open heart surgeries by electrolytes, because they help to regulate myocardial and neurological function, fluid balance, oxygen delivery, acid base balance, and electrolyte imbalance causes excessive ingestion or diminished elimination of an electrolyte or diminished ingestion/excessive elimination of an Electrolyte . (8) .

 Hypernatremia  is the cause of too little fluid as seen with dehydration, not too much sodium caused by potassium depletion from vomiting, diarrhea, excessive administration of diuretics or sodium bicarbonate, hypernatremia is a serious electrolyte imbalance after surgical repair of the heart, it can cause significant neurological, endocrine and cardiac disturbances,

hypernatremia causes a shift of water out of cells making the cells dehydrated.(9,10,11).

      Following low-sodium diet helps control high blood pressure, edema and decrease breathing difficulties, however, seriously ill patients who are immunocompromised and /or have altered flora may be unable to adequately resist   microorganisms introduced via enteral feeding. (12). Fats stimulate the gall bladder and liver to release bile, and the breaking down of the protein is a putrefying process which exposes the sores, ulcers, and inflamed areas of intestinal tract to further irritation, may potentially serve as opportunistic pathogens in the GI tract, producing diarrhea.(13).Any diary products have a protein that is very difficult for the human digestive system of Dawn syndrome child with cognitive disabilities especially milk and ice cream ,are one of the major offending factors in inflammatory bowel disorders.(14). While Low pH of the stomach and decreased thyroid hormone among Dawn syndrome children with congenital heart defects as well as small diameter of the oral cavity, low salivary secretions and small structure of the teeth, it consider as a resk factors for constipation  (15). Also.CCU patients after heart surgeries often receive antibiotics that may alter the normal bowel flora leading to bacterial over growth, bacterial entry into the small intestine .(16). Functions of

 phosphorus help in the metabolism of carbohydrates, protein, fats, maintenance of acid-base balance, promote white cell, while hypophosphatemia can occur in increased urinary losses, vomiting, diarrhea and hyperventilation and the patient at the acute stage are suffering from confusion, seizures, coma, chest pain, munbness, tingling of fingers and lips, decreased muscle strength.(17). The patient at chronic stage with hypophosphatemia are suffering from memory loss, bone pain, lethargy, joint stiffness, and cyanosis, and the risk factors for hypophosphatemia after rapier heart surgery are respiratory alkalosis, increased urinary losses, diuretics, reduced intestinal absorption and it is common among Down syndrome patients, vomiting and diarrhea . (18).  At least three normal defense mechanisms are altered in CCU patients, which may make them more vulnerable to ingested bacteria:1)no salive,2)pH alterations, and ( 3)

antibiotic therapy, under such conditions, even relatively small amounts of ingested bacteria may then contribute to the development of diarrhea .(19).Hypoventilation related to depressant effects of anesthesia and some medications(e.g. narcotic analgesics, muscle relaxants), weakness, chest incision pain and hyperventilation related to : excessive ventilatory assistance, and  improving breathing pattern by the chest tube is sutured in place and  maintain adequate systemic tissue perfusion .(20). Pediatric corrective heart surgery requires cardiac rehabilitation, long-term follow-up care as well as follow up by a family practitioners, especially with children who have undergone at a very early age, and patients who are diagnosed with congenital heart disease at older age, families have the right and the authority to care for their children, as partners in care, professional staff and family members work together as collaborations in the best interest of the child, within the application of Self-Care Program to be an independent child.(21).

Background and Significance

The incidence of CHD is estimated to be between 5 and 8 per 1000 live births, and many will require surgical interventions ,while sixty-nine percent 69% of all Atrial Ventricular Defects have Down syndrome, The Ebstein`s malformation mortality in children presenting in the neonatal period is 30-50%,mortality is higher with severe right Atrial enlargement,, right ventricular dysplasia ,and it is noted that mortality rate is higher in patients with other associated congenital heart diseases ,when presentation is in infancy and with severe cyanosis or congestive heart failure.(22,23).The incidence of admitted neonatal and children patients with Dawn syndrome and requiring surgical interventions at Cincinnati Medical Center, Ohio .USA, and their ages ranged between (6 months-7 years old )from October 2000 until May  2004 it was 1256 .(24).The admitted patients  with Down syndrome and requiring surgical repairs at The National  Institute for Heart . Cairo, Egypt from February 2001 until September 2004 it was 420 patients their ages ranged between (2  –6 years old)  (25).

      Back, neck and low shoulder pain often occurs after surgery, this discomfort can be relieved with a heating pad set for a 10-15 min, 3 to 4 times a day, do not use on Incisional areas, heating pads should not be used for diabetic patients, and application of cardiac rehabilitation program followed by home care instruction to the parents reduce limitation and improve the level of independence.(26).

     Postoperative neuralgic complications include; seizure disorders; and cognitive, language, behavioral, and social problems, also heart surgical techniques may be relatively straightforward or extremely complex, the degree of complexity usually reflects the degree of risk involved, and is further heightened by risks and conditions associated with newborn immature organ systems, as well as associated with congenital abnormalities that accompany congenital heart disease.(27).

Aim of the study

1-Apply Cincinnati Children’s Down syndrome Program Care for Down syndrome at Coronary Care Unit after surgical repair.

2-Follow-up of the patient’s condition at the Coronary Care Unit and outpatients Clinic for the prevention of complications.

3-Assess the levels of functional independence in children with congenital heart defects before and after surgical repairs.

Hypothesis

Theoretical framework- Abdellah, F.G Model (28) formed the theoretical framework for this study. Identify five basic elements as the following:

1- Instructing children and families .2-Observation and reporting the present signs and symptoms.3-Interpretation of signs and symptoms.4-Analysis of nursing problems.5-Organization to ensure a desired outcome. Its goals providing a nursing care plan to meet the patient’s individual needs are basically physical, biological, and social-psychological, helping the individual to become more self-directing in order to maintain health of mind and body, assisting children to become independent so as to achieve the goal of health, by instructing the parents to help the child or neonate do for himself what he can within his limits, helping children adjust to their limitations and emotional problems, by the application of immediate post-operative observational  list ,Cardiac Rehabilitation Program ,Self-Care Program for the Down syndrome neonates and children  with congenital heart defects and their parents .

Material and methods-A consecutive series of Down syndrome young children with Congenital Heart Defects (CHD) who underwent Open Heart Surgery at National Institute of Heart .Cairo, were recruited before surgery and are being followed prospectively. The study sample was started at November 2001until November 2004, Immediate postoperative cardiopulmonary, neuromuscular, and gastrointestinal assessments, applications of Self-Care Program as regard the child cognitive, motor, musculoskeletal and bawel disabilities and cardiac rehabilitation at the fifth day and follow up of the child’s condition after one, six month and after one year.

Sample of the study-The sample of the study was a stratified random sample

Sample size-The sample size for this study was based on Cohen`s formula for multiple regression (29).(N=Lambada/f2),in this case the effect size of 0.25 was used. An alpha of 0.05 is considered a convention for significance. Lambada is determined to be 7.8,N=7.8/0.25 = 31.2,there are one independent variable and three dependent variable. In this study sample 93 was recommended.

Functional Measures

 (1) Immediate post-operative cares following cardiac surgery for Cincinnati Pediatric Hospital (30)                                                                     

-Suitable positioning on the bed (a semi-to high Fowler’s position)

2-Monitoring for Catheters:

1-Oxygen therapy.

2-Central Venous Pressure.

3-Open thoracic drains (place thoracic drainage bottle in a suitable recipient).

4-Check position of nasogastric tube

5-Investigate the position of the tracheal cannula and its correct fixation

-Set respirator parameters, connect the patient to the respirator

-Physical evaluation: skin and mucous color, capillary refill, level of hydration

-Routine tests are requested sodium, potassium, calcium, glycemia, hematocrit, and hemoglobin three times a day for the first 2 days and once a day after extubation and hemodynamic stabilization, uric acid, coagulation tests and creatinine are requested daily.

3-Basic Monitoring:

1- Heart beat for detecting cardiac arrhythmia.

2- Arterial pressure for measurement of diastolic and systolic pressures continuous infusion of heparin with saline (1U/ml).

3-Central Venous Pressure or right atrium pressure to evaluate right ventricle function.

4-Urinary output folly catheter is fitted .

5-Nasogastric tube is maintained open at least.

6- hour post-extubation.

 7- Mediastinum and/or pleural drains.

8- Rectal temperature every 15 min during the first hour and then every 30 min during the second hour then every 4 hour until the first 24 hour after operation.

4- Invasive Monitoring:

1-Pulmonary artery pressure (measured with a Swan –Ganz Catheter).

2-Cardiac output (using a Swan-Ganz) .

3-Central Venous Pressure                                                                                                                       

5-Observational Sheet for Complications

during immediate post-operative period (31)

As the following:

1-Alteration of systemic tissue perfusion.

2-Hypovolemia.

3-Impaired gas exchange.

4-Respiratory acidosis.

5-Respiratory alkalosis.

6-Hyponatremia.

7-Hyperkalemia.

8-Hypoclcemia.

9- Metabolic  acidosis Participant inclusion criteria included those with a diagnosis of Congenital Heart Diseases undergoing their first Heart surgery, their ages ranged between (2 to 12 years old).

         Participants were excluded if there were known risks for neuralgic defect. These would include the following:1)prematurity or small for gestational age,2)clinical evidence of a central nervous system anomaly(eg,brain malformation) or insult (eg, perinatal asphyxia).

Categorical risk factors included: type of Congenital Heart Defects (i.e., cyanotic Vs acyanotic), low arterial oxygen saturation (PaO2<85) before surgery, type of cardiac surgery (i.e., corrective VS palliative), and parents education or one will take care of the child (more than high school), intraoperative procedures, length of stay in intensive care (days), total duration of hospitalization (days), and number of subsequent hospitalization and cardiac surgeries.

Functional Measurers:

 The WeeFIM instrument (32) is a pediatric functional independence in children aged 2 - to 6 years, contains 18 items across the domains of self-care (6 self-care and 2 bowel and bladder management items), mobility ( 3 transfer and 2 locomotion items), and cognition(2 communication and 3 social cognitive items). Self-care items examine how independent a child is in eating, grooming, bathing, upper body and lower body dressing, and toileting. The mobility domain includes chair/wheelchair, toilet and tub/shower transfers, and locomotion with respect to walking, use of wheelchair or crawling and going up/down stairs.. The cognition domain examines how well a child expresses his/herself and understands communication. This domain also comprises social interaction (e.g., skills related to getting alone and participating with others in play situations). In addition, problem solving is addressed by assessing a child’s ability to solve problems of daily living and memory (e.g., remembering daily routines, recognizing familiar people). Each item is rated on a 7-point ordinal scale ranging from 7(complete independence) to 1 (total assistance). A moderate disability is defined as scores falling between (50 to 75), whereas a severe disability encompasses scores below 50 and would include children who are essentially fully dependent in self-care and mobility.  The WeeFIM is a 7-level criterion-specific ordinal scale as the following: Therefore the minimum score is 18 with maximum of 126, in self-care, the range of score are8 to 56,in motor, the range of scores are 5 to 35,in cognition, the range of score are 5 to 35.

Potential Cardiac Complications Sheet. (33)

          Home Care after Heart Surgery-Instructions for parents  (34),is a structured program of education and activity guided toward lifestyle modification ,increasing functional capabilities and peer support it generally includes: Care of the incision, exercise program, diet instruction, instructions about medications, Bladder & Bawel training program and when parents must call doctor. Pain and music therapy.(35).Most children are experiencing mild, moderate discomfort and disturbances during sleeping from feeling pain at the incision site after heart surgery. Chest pain is not unusual to a child, music therapy was used to reduce pain. Firstly the researches measure pulse rate, blood pressure, Pain Scale and respiratory rate, then patient listened to 30 min cassette recording of selected relaxing or funny music, patients were able to choose the type of music that was most preferable and relaxing to them from a three-minutes test tape of the various types of music, remeasure pulse rate, respiratory rate, Pain Scale and blood pressure after hearing music therapy.

Note: these instructions for children and their parents

-     Get plenty of rest

-     Child’s body requires six to eight hours of sleep every night

-     Do not exercise for at least one hour a heavy meal                                          

-     Do not exercises during the most severe stages of a cold or other illness and never exercise with a fever  Walk at a comfortable rhythmic pace

-     Avoid bursts of speed, worm up and cool down for 5 min at a slower pace                        

-     Count radial pulse rate and do not start exercises if pulse rate below 60b/m ,or above 120 b/min, do not allow pulse to increase more than 80b/min ,warm-up for 5 min ,Cool-down for 5 min and walking gradually .                                                       

Week (1) walk 3-5 min, three to four times daily (total 12-20min), may walk through several rooms in home, outdoors in good weather                                                      

Week(2) walk 7-10 min, two-three times daily(total 21- 30 min), begin to increase activity .  

Week(3) walk 10-15 min ,two times daily (total 20-30 min).  

-     Avoid arm activities that involve lifting, pulling or pushing.

-     Do not strain to open jars or stuck windows                                                            

Week (4-6), walk (15-20)min ,one-two times daily(total 30 min).bicycling.

How much activity is OK?

- Get plenty of sleep at night

- Space meals and activities to allow time for rest and relaxation

- Stop and rest when tired

Avoid the following activities, which increase heart rate and blood pressure and put excess pressure on incision after surgery:

-     Pushing, pulling, or weight lifting

-     Straining to open a window or jar lid

-     Excessive straining to have a bowel movement

-     Avoid standing up too quickly from a sitting or lying position

-     Sudden changes in position may cause light headaches

-     Concentrate on breathing normally through any exertion or activity (exercise, bowel movement

-     Avoid extremes of temperature, hot or cold temperatures, which increase the workload on the heart.

When to stop exercise?

Your body may tell you to stop exercising by giving you the following warning signs:

           If you get any of these signs, stop working out, go away for rest and call your doctor.

10- What Care is needed for the incision?

-     Clean incisions daily with soap (non-deodorant or non-perfume) and water.

-     Do not cover incisions with anything other than clothes, if there is drainage loose, gauze-type bandage can be paced over it.

-     Cream, ointment, or powders should not be applied for 6-8 weeks.

-     After 6-8 weeks when the scares are fully healed rub Vaseline, lanolin, and vitamin E on the scars to help soften and decrease the scarring.

-     Examine incisions twice a day.

-     Report any significant changes, such as: redness, swelling, or drainage.

-     Temperature should be taken twice a day, once on the morning and once in the evening.

-     Keep the graft leg elevated when sitting to prevent swelling in the foot and ankle.

-     Keep a daily diary of temperature, weight, appearance of incisions and distance walked each day.

-     What symptoms can be expected after discharge from the hospital?

-     Tingling, numbness, burning or itchiness around incisions will gradually lessen with time.

-     Tender spots on the chest may be noted along side the incision.

-     Some deep muscle aches and soreness are common IF

-     Chest discomfort is described as pulling, sharp, aching or soreness.

-     Incisional discomfort in the chest may persist for 2-3 months or longer until the breastbone heals completely.

-     Drainage, increased redness or swelling in incision.

-     The patient may feel a slight motion or clicking in the breastbone after 2 months with sneezing, coughing, deep breathing or changes of position.

-     IF this continues beyond 2 months, the parents should notify the surgeon.

11- White Diet (42)

Chest Physiotherapy. (36) is the removal of excess secretions from inside the lungs, by physical means, it is used to assist a cough, re-educate breathing muscle and to try to improve ventilation of the lungs.

- Medications (37): It is very important for the parent to have informations about their child’s medications (Appendex2)

     A longitudinal study was carried out in 3 phases.

First Phase: Selection of Dawn syndrome children with congenital heart defects according to the inculcation and exclusion criteria of the study from outpatient cardiology clinic of Naser Heart Institute.

Second Phase: Immediate post-operative care in Cardiology Intensive Care Unit, and application of Cardiac Rehabilitation.                                                                         

Third Phase: Evaluation of the patient’s condition, one, six months, and after one year.

Statistical Analysis: - Assessment of the child condition immediately after operation and then after one month by paired sample statistics, paired sample correlation, by using SPSS.

Results: Patient recruitment 93 patients presented the following characteristics:

(18 with Atrioventricular Septal Defect, 20 with Pulmonary Stenosis, 20 patient with Coarctation of the Aorta, 15 with Ebstein`s anomaly, 10 with Tetralogy of Fallot ). Their ages ranged between 2-12 years old (50 boy and 43 girl). Table (1) Demonstrated mean score of temperature, pulse, respiration, and systolic and diastolic blood pressure immediately after operation, after 15 min, after 30 minutes and there was an improvement of vital signs. Table (3) Mean score of 24 hours urine collection after operation and at the fifth day there was an improvement. Table (4) Paired samples Correlations of Arterial Blood Pressure immediately after operation and at the fifth data and there was a highest Correlations are regard HCO3 (.187) while the lowest correlation as regard (pH). Table (5) Demonstrate an improvement of Hemodynamic Monitoring of the patients immediately after operation, after one hour and after four hours. CVP was improved (2.7077-4.1075-5.3767) also Pulmonary artery pressure was improved (5. 505-8.860-9.344)and Cardiac Output was improved (7.440-7.043-5.731).Table (6) Demonstrated Potential Cardiac Complications and it was arrhythmias 10%, Congestive heart failure 3%, Postpericardiotomy syndrome 2%, Cardiogenic Shock 2%.

Results

Table (1) Mean score of temperature, pulse rate, respiratory rate, systolic and diastolic blood pressure immediately after operation, after 15 min, and after one hour

Vital signs	X	SD	t test
Temperature Immediately After 15 min After one hour Pulse rate Immediately After 15 min After one hour Respiratory rate Immediately After 15 min After one hour   Systolic pressure Immediately After 15 min After one hour Diastolic pressure Immediately After 15 min After one hour	37.139 37.043 36.989   81.957 77.290 70.161   9.989 9.612 12.322   102.505 118.139 97.311   75.107 74.408 82.946	.962 .735 .773   14.688 9.404 8.068   2.223 1.707 1.376   13.743 16.762 12.215   4.241 4.535 7.632	372.219 485.     406 461.394     53.810 79.2       55 83.863     43.129 54.3

Table (2) Mean score of 24 hours Urine Collection   after operation and at the fifth day

Urine analysis	X	SD	t test
Creatinine During first 24 h At the fifth day Urea Nitrogen During first 24 h At the fifth day Sodium During first 24h At the fifth day Chloride                During first 24 h At the fifth day Calcium During first 24h At the fifth day	1.451 2.010   9.365 15.247   78.129 160.849   161.258 190.612   28.258 41.086	.500 .914   3.243 1.256   42.512 20.077   133.643 48.624   8.918 9.505	27.978 21.197   27.850 116.998   17.723 80.141   11.636 37.804   30.555 41.681

Table (3) Paired Sample Correlations of Arterial Blood Gases immediately after operation and at the fifth day

Arterial blood gases	Correlation	Sig.
PO2 Immediately after operation At the fifth day PCO2 Immediately after operation At the fifth day   pH Immediately after operation At the fifth day HCO3 Immediately after operation At the fifth day SO2 Immediately after operation At the fifth day	.121     .034       .069     .187     .036	.247     .748       .509     .072     .730

Table (4) Mean Score of Hemodynamic Monitoring immediately after operation, after one hour, and after four hours

Hemodynamic	X	SD	t. test
1-CVP immediately after one hour after four hours   2-Pulmonary artery pressure(Swan-Ganz) immediately after one hour after four hours 3-Cardiac output immediately after one hour after four hours	2.7097 4.1075 5.3763       5.5054 8.860 9.344   3.440 7.043 5.731	1.128 1.1338 .991       1.247 1.735 6.397   7.435 1.293 1.311	23.156 29.585 51.896       42.598 49.226 14.686   9.650 52.526 42.137

Table (5)Numbers of WeeFIM Pediatric Functional Independence for children with Dawn syndrome and congenital heart defects after the application of Self-Care Program at the fifth day of surgery and after six month

Scale	Fifth day	After six months
1-Self Care -Complete independence -Moderate assistance -Total assistance 2-Mobility -Complete independence -Moderate assistance -Total assistance 3-Cognitive -Complete independence -Moderate assistance	- - 93                     -   10                 83                      -   30   63	-                    55     38   40   53     -   45   48

Table (6) Percentages of Potential Cardiac Complications for Down syndrome children with Congenital Heart defects after Heart Surgery 

Potential cardiac complications	%
Arrhythmias Congestive Heart Failure Postpericardiotomy syndrome Cardiogenic Shock	5% 3% 2% 2%

Discussion

       Pediatric corrective heart surgery requires long - term follow – up care by a pediatric cardiologists, nurse specialists as well as routine follow up by a family, especially with children who have undergone repair at a very early age.(38).The present study was applied Cincinnati children’s Down syndrome program with Congenital Heart Defects the from table (1-16) demonstrated that there were an improvement of the patient’s conditions,also the attendance of parents during Cardiac Rehabilitation program and Self-Care program for their children lets the children to feel safe and it consider as an excellent cooperation between the health team and the child’s family as well as it reduce the parent’s anxiety ,and Table (16) clarify these facts ,while the health team tends to do very well after open-heart surgery, the risk of untoward complications is relative to the magnitude of the operative procedure. This, in turn, relates to the complexity of the underlying congenital heart disease; decreased cardiac output related to hypovolemia associated with persistent bleeding post-operatively; excessive loss of fluids resulting from nasogastric tube drainage, vomiting, diuretic and decreased fluid intake; also as a result of hypotension associated with hypovolemia as a result of rapid body warming following surgery, decreased mobility (39). Maintain adequate cardiac output: place patient in a semi-to high Fowler`s position, instruct patient to avoid activities that create a Valsalva response, oxygen therapy, small and frequent nasogastric meals perform actions to prevent hypotension by monitoring B/P before and after administering negative isotropic agents (e.g. propranonl), vasodilators,and narcotic analgesics, consult physician before giving negative inotropic and vasodilating agents if B/P is below 11/70 mm Hg.(50), the present study revealed as regard table (2) mean score of vital signs immediately after operation, after 15 min and after one hour, and there were an improement, while table(3) revealed that there were an improvement of 24 hour urine collection after operation and at the fifth day ,represented by creatinine clearance, urea nitrogen, sodium, chlorid, calcium, and as regard (4) demonstrated paired sample correlations of arterial blood gases immediately after operation and at the fifth day, also as regard table (5) Hemodynamic monitoring immediately after operation ,after one ,and four hours were improved also as regard table (6)Demonstrated an improvement  of CVP, plumonary artery pressure (Swan Ganz), cardiac output of the patients were improved, also as table (8) presented the percentages of immediate post-operative complications ,after one ,four  and six hours, also table (9&10) and there were an improvements. Ineffective airway clearance related to: stasis of secretions associated with decreased activity and poor cough effort resulting from depressant effects of anesthesia and some medications (narcotic analgesics, muscle relaxants) pain, weakness, and fatigue, increased secretions associated with irritation of the respiratory tract. (40). Facilitate removal of pulmonary secretions  by liquefy tenacious secretions: maintain a fluid intake of at least 2500cc / day unless contraindicated, humidify inspired air ,assist with administration of mucolytic agents via nebulizer or IPPB treatment, instract and assist patient with effective coughing techniques every 1-2 hours unless contraindicated., tracheal suctioning. (41) . Maintain adequate systemic tissue perfusion by preventing peripheral pooling of blood by instructing patient in and assist with active foot and leg exercises for 5-10 minutes every 1- 2 hours, discourage positions that compromise blood flow in lower extremities (e.g. crossing legs, pillows under kness),change positions slowly to allow time for autoregulatory mechanisms to adjust to position changes, avoid exposure to cold causes generalized vasoconstriction.(42). The incidence of gastrointestinal disturbances after open heart surgeries due to several causes such as infection, antibiotics and narcotics muscle relaxants and applying the principals of aseptic techniques for preparing food for nasogastric feeding decreases the incidence of these disturbances (43). Encourage patient to drink warm liquids to stimulate, apply heat to the abdomen for 20 minutes every 2-3 hours unless contraindicated, consult physician regarding insertion of a rectal tube, avoid gas-producing foods / fluids (e.g. carbonated beverages, baked beans) for abdominal discomfort.(44).Eliminate noxious sights and smells from the environment (noxious stimuli cause cortical stimulation of the vomiting center),also encourage patient to take deep ,slow breaths when nauseated ,instruct patient to change positions slowly (movement stimulates the chemoreceptor trigger zone) and the immediate post-operative care of Cincinnati Hospital at Critical Care Units after Open Heart surgeries, and the patient’s conditions were improved after the application of a White Diet( 45) ,is a program diet that is restful the digestive tract at the same time will provide a person with the nutrients necessary to go on with life ,and it consists of general instructions as well as program of 12 days and the present study revealed that there are an improvement of gastrointestinal disturbances after the application of this program. Bacterial Endocarditis is consider as a serious complication after open heart surgery while accurate oral care from the first moment after operation prevent the occurrence of these problem by (physiological saline solution 0.9%or by hydrogen peroxide (teaspoonful +cup of warm water gargling or topical application of the oral cavity three times per day).The use of music as a nonpharmacologic method for treating pain has recently become a topic of interest among health professionals, the physiological and psychological effects of music, including the capacity to increase or decrease muscular energy to affect volume of pulse and blood pressure and to alter mood (46). The use of music during postoperative care was found to decrease overt pain reactions and levels of required pain medications, musical tones characterized by harmonic intervals, gentle steady rhythms, and flowing melodies create pleasing sensory experiences for the patient. General physical and emotional relaxation occurs along with diminished awareness of pain ,foods that are high in potassium is very important after surgery , following diuretics and coronary dilators because potassium level will drop and patient will suffer from the following: fatigue, weakness, severe thirst, excessive urination, changes heart beat ,also improve the abdominal and bladder binder and is very effective for the children with urinary incontinent as well as practicing  bladder training  exercise program(47), and the present illustrated an improvement after 6 months after following the nutritional program and practicing the bladder training program also families were cooperative during program .

Conclusion and Recommendation

1-The provision of adequate, effective observation for the child with Down syndrome immediately after congenital heart defects surgery prevent the possibilities of immediate and late post-operative complications and improve the child condition.

 2- The cooperation between the health team and parents for follow-up care at home is very important stage of the rehabilitation program after congenital heart defects surgeries.

 3- The provision of adequate rehabilitative, social, and environmental support wills ultimately improves functional outcomes and ease burden of care.

 4- Increase functional capacity, the ability to carry out activities, reduce risk factors of immediate and potential complications by follow up of the child’s condition from the first moment of his/her arrival to the Heart Institute, per-post operative period, then follow-up at Cardiology outpatient clinic and attend family –care program improve quality of life and emotional stability of the child.             

5- Furthermore, early remediation strategies and compensatory techniques may be implemented to increase functional independence and enhance the health and well being of the child and family.

References

1.    J.A.Conner, R.R. Arons, M.Figueroa, and K.M. Gebbie. Clinical Outcomes and Secondary Diagnoses for Infants Born with Hypoplastic Left Heart Syndrome. Pediatrics, August1, 2004; 114(2): el60 - e165.

2-Limperopoulos C, Majnemer A, Shevell M. Rosenblatt B.Child with Down syndrome and congenital heart defects before and after open heart surgery.Pediatrics.2003; 203:234-239

3-Bellinger DC, Rappaport LA, Wypij D. Patterns of developmental dysfunction after surgery during childhood period to correct transposition of the great arteries .J Developmental Behavior for Pediatric .2003; 23:901-908.

4-Hovels- Gurich HH, Seghye MC,Dabritz S,Messmer BJ. Cognitive and motor development among Down syndrome with congenital heart defects . J Thoracic Cardiovascular Surgery. 2003; 321: 654- 660.

5-Blackwood M, Haka- Ikse K,Steward D. Developmental outcome in children undergoing open heart surgery. Anesthesiology . 2003 ; 109: 876-880.

6-Ferry PC. Complications after cardiac surgery in children. Am J Dis Child .2003; 4:765-770.

7- Dougherty M, Wright FS, Garmezy N, Loewenson RB,Torres F.Late competence and adaptation in children who survive severe heart surgeries. Nurs Clin North Am. 2004;5:654-660.

8- Msall ME, Rogers BT, Ripstein H. Measurement of functional outcomes in children after congenital heart surgeries. Physical Med Rehab Clin North Am.2003;7:989-990.

9-Miller G,Tesman JR, Ramer JC,Baylen BG. Outcome after open heart surgery in infants and children.J Child Neurol.2003;11:667- 670  .

10- Hagemo PS,Rasmussem M, Bryhn G,Vandvik I. Hypoplastic left heart syndrome: multi- professional follow -up in the mid - term following palliative procedures. Cardiol Young . 2003;7:567-570.

11-McCabe M,Granger C.Content validity of a pediatric functional independence measure. Appl Nurs Res.2003;6:234-240.

12-Msall ME. Functional assessment in neurodevelopmental disabilities. Phys Med Rehab Clin North Am.2003;4:654-660.

13-Mendoza JC, Wilkerson SA, Reese AH. Follow-up of patients who underwent arterial switch repair for transposition of the great arteries. Am J Dis Child .2004; 230: 671-680.

14-Oates RK, Simpson JM ,Cartmill TB, Turnbull JA. Intellectual function and age of repair in transposition of the great arteries inchildren.N Engl J Med.2004;80:765-770.

15-Clarkson,PM,MacArthur ,BA, Barratt- Boyes, BG, Whitlock RM.Cognitive development of children following early repair of transposition of the great arteries .Pediatrics.2004;98:978-991.

16-Limeropoulos C,Majnemer A,Shevell MI, Rosenblatt B.Outcome of children with congenital heart defects one year following open heart surgery. Cardiol Young.2004;8:897-912.

17-Kramer HH, Awiszus D,Sterzel U,ET AL. Development of personality and intelligence in children with congenital heart disease. J Child Psychol Psychiatr.2004;50:543-550.

18-Dolk H. Congenital brain anomalies associated with hypoplastic left heart syndrome. Pediatrics. 2004;89:1102-1110.

19-Bashour CA,Yared JP, Ryan TA,ET AL. Long-term survival and functional capacity in cardiac surgery patients after prolonged intensive care.Critical  Care Med.2004;56:678-686.

20-Sanderson JM, Wright G, Sims FW. Immediate post-operative care after congenital heart defect surgeries. Thorax 2004;87:987-996.

21-Ferry PC.Self-Care after Congenital Heart Defect surgery for Dawn syndrome child. Am J Dis Child 2003;213:985-995.

22-Hovels.KL.Gurich HH. Cognitive disabilities and Congenital Heart defect surgeries J Thorac Cardiovascular Surgery; 321: 675-682.

23-Kunan KC, et al. Congenital heart defect surgeries and immediate post-operative period.Circulation:2003;203:895-920.

24-Miller G, Ekkli KD, Contant C. Epidemriology of congenital heat defects among Dawn syndrome children. Arch Pediatr Adolesc Med 2004; 341:560-569.

25-El-Shamy FR. Incidance of Dawn syndrome children with congenital heart defects at National Heart Institute of Egypt. Unpubilished Master Thesis .2001:39-40.

26-Gillon JE. Immediate post - operative complications after congenital heart defects surgeries. Pediatric Cardiology. Edinburgh, Scotland: Churchill Livingstone;2003:5-17.

27- Bellinger CD, Janas RA, Rappaport LA . Follow-up of patients after congenital heart defects surgeries. J Critical Care Med . 2004 ; 659 : 1098 - 1115.

28- Abdellah, F.g., I. l. Beland, A. Martin, and R . V . Matheney. Patient-Centered Approaches to Nursing . New York : Macmillan, Inc., 1990.

29- Cohen`s Formula. Calculation of Sampling size. Case Western Reserve University Cleveland Ohio.2000.

30- William C, Hans JR. Immediate post-operative cares following cardiac surgery for Cincinnati Pediatric Hospital 2003.

31- William C, Kelly FH, Moore S. Observational Sheet for Complications during immediate post-operative period for Dawn syndrome children with congenital heart defects. Cincinnati Medical Center and University Hospital of Cleveland ,Cleveland Ohio.2003.

32- Hamilton, B, B., Granger, C.V., Sherwin, F.S., Zielezny, M. The WeeFIM Functional Independence Measure (for Children).Buffalo, NY: Buffalo General Hospital State University of New York at Buffalo.2002.

33- William C, Robert R. Potential Complications after Congenital Heart surgeries for Dawn syndrome children with congenital heart defects Cincinnati Medical Center .2003.

34- Moore .S, William C. Home Care after Heart Surgery –Instructions for parents. Cincinnati Medical Center for Dawn syndrome children undergoing to open heart surgeries and Case Western Reserve University ,University Hospital of Cleveland.2003.

35- Marrion Good. KL Efforya . Pain after open-heart surgeries among children and music therapy. Case Western Reserve University Cleveland Ohio, and Cincinnati Medical Center for Dawn Syndrome children after congenital heart defects surgeries.

36- Dablen MK, William. RE. The . Rate of Perceived Exertion Scale. Cincinnati Medical Center for Children with Dawn syndrome and congenital heart defects, Ohio State .2003

37- Ferry.P Karren. White Diet and Irritable Bawel Syndrome among Dawn syndrome after congenital heart defect surgeries. Cincinnati Medical Center for Dawn syndrome Children, department of parent’s instructions.2003.

38- Duller.EK.Chest Physiotherapy after heart surgery. Cincinnati Medical Center after Heart surgeries for Dawn syndrome children.2003.

39- Miller KM. Patient and family informations about medications. Department of Pharmacology. Case Western Reserve University, Faculty of Medicine, Cleveland Ohio.2003..

40 - Utens EM, Versluis - Den Bieman HJ, Verhulst FC, Witsenburg M. Psychological distress and styles of coping in parents of children awaiting elective cardiac surgery. Cardiol Young . 2004 ; 10 : 435- 445.

41- Kong SG, Tay JSH, Yip WCL, Chay SO. Emotional and social effect of congenital heart disease in Singapore. Austr Pediatr J.2004; 56 : 543- 550.

42- Golderg S, Jans M, Washingtone J, Simmons RJ. The impact of maternal perceptions and medical severity on the adjustment of children with congenital heart disease 57-47-Kurtzberg D, Vaughan HJ, Daum D. Pediatric intensive care after congenital heart defect surgery. Arch Pediatr Adolesc Med.2004;18:349-259.

43- Vohr BR, Msall M. Immediate post-operative care for Dawn syndrome child after congenital heart defect surgery.Crit Care Med. 2004; 54 : 765 - 773.

44- Nuutinen M, Koivu M, Rantakallio P. Long –term outcome for children with congenital heart defects. Arctic Med Res 2004;56:459- 568.

45- Perry LW, Neill CA, Ferencz C, et al. Infants with congenital heart disease and post 51–operative complications. Am Dis Child 2004; 43:439-451.

46- Clare MD Home care of infants and children with cardiac disease. Heart Lung 2003;45:871-884.

47- McCabe M, Granger C. Congenital heart defect surgery and Rehabilitation Care for children.. J Child Neurol.2003; 12:87- 99.

1- The Wee FIM (Functional Independence Measure

2- Cincinnati Children's Down syndrome program (Immediate Post-operative Care and Home care after heart surgery)

3- Gastrointestinal symptoms Rating Scale

4- Johnson`s Sensation and Distress of pain Scale.

5- Constipation &Diarrhea Rating Scale

6- The Rate of Perceived Exertion

7- Disability Rating Scale

8- Hamiliton Anxiety Scale for Parents.

9- Bladder7Bawel Training Program

10- Self-Care Program for Down syndrome

11- Zung`s Anxiety Rating Scale for children undergoing heart surgery.

Down syndrome in Egypt

Ezzat Elsobky and Solaf M. Elsayed

Pediatrics Hospital, Ain Shams University

Abstract

        Down syndrome (DS) is the most common and best-known chromosomal disorder and is the single most common genetic cause of mental retardation. Governmental care of this syndrome and other handicapping conditions has increased tremendously in the past few years to the extent that DS phenotype has became a phobia and many parents and/or physicians referred normal babies for karyotype for suspicion of chromosomal anomalies or  for reassurance of their parents. On the other hand, prenatal screening is still inaccessible to most families and almost all cases of Down syndrome are diagnosed postnatally. 

        In this paper we present the first and the largest study on DS patients referred to Medical Genetics Center from different regions and discrete all over Egypt aiming to look for possible causal factors for this high birth rate, and to evaluate the trend of parents and clinicians to the new screening programs and prenatal diagnosis. The study was included 1100 patients referred as DS, 1030 cases were confirmed by cytogenetic analysis to be DS. Most of these cases (98.43 %) were diagnosed postnatally and only 1.56 % were detected prenatally mainly through amniocentesis and rarely products of conception (0.01 %). Their ages ranged from one hour to 30 years with mean of 351 days. Males represented 54.13 % while females represented 45.87 % of the studied group. Mean maternal age at conception was 31.8 years for cases with non- disjunction and 24.5 years for cases with translocation. All mothers of cases of translocation DS were under 35 years, in contrast to mothers of non- disjunction cases in which 41.48 % were above 35. Paternal age ranged from 19 to 62 years with mean of 36.5 years in non-disjunction cases and from 24-35 years in translocation cases with mean of 30.6 years. Consanguineous marriage was present in 12 % of cases. Positive family history was present in 6 % of cases. Most of cases were the first or the second in order of birth, and the most common cause of referral was dysmorphic features in live births and advanced maternal age in prenatally referred cases.

       Karyotype revealed that 93.98 % of cases had non-disjunction, while 3.5 % of cases had translocation and 1.84 % had mosaicism. Non- classical karyotype was present in 7 cases (0.68 %). Most of the cases of translocation with (21; 21), which was present in 51.35 % of cases, followed by t (14; 21), which was present in 40.5 % of cases, t (13; 21) in 5.4 %, and t (15; 21) in 2.7 % of cases of translocation. We concluded that, in Egypt 1.6 million births / year and estimated risk of 2285 DS births annually, the concept of preventive genetics should be reinforced with a national policy targeting both health professionals and general publics to offer prenatal genetic screening for all pregnant ladies and prenatal diagnosis for screen  positive cases. This needs an integrated system including proper integrated diagnostic facilities, trained personnel and professional staff.

Introduction

Down syndrome is the most common and best-known chromosomal disorder. Although prenatal screening and diagnosis have expanded dramatically in the past few years, it is not always accessible in developing countries like our country and so we still have a very high birth rate of Down syndrome.  In this paper we present the first and the largest study on Down syndrome patients referred from different regions and discretes all over Egypt in a trial to search for possible causal factors and to study the response of parents and clinicians to the new screening programs and diagnosis.

Materials and methods:

The study was included one thousand and one hundred cases - refereed as DS- from different regions and discretes all over Egypt from January 1996 to October 2003. For all cases routine G- banding cytogenetic analysis was done and extended mosaic study was performed when indicated. Cases confirmed to be DS were then classified into two groups according to the time of diagnosis: prenatal and postnatal diagnosed cases.

Results:

The study was included 1100 cases, 93.64 % (1030 cases) were confirmed to have DS by cytogenetic analysis and 67 cases confirmed to have normal karyotype and 3 cases had abnormal karyotype, table (1).

 

karyotype	Number
Down syndrome	1030
46, XX or 46, XY	67
46, X, I (Xq)/ 45, X	1
46, XX, add (15) (q26)	1
46, XY, add (3)(p25)	1

Table (1): karyotype of the referred cases. 

Cases confirmed to be DS then classified into two groups according to the time of diagnosis: prenatal and postnatal diagnosed cases. Most of them (98.43 %) were diagnosed postnatally and only 1.56 % were detected prenatally ( among 1022 cases of amniocentesis referred for advanced maternal age, previous history of DS or positive prenatal screening test), while 0.01 % were products of conception. The ages of postnatal cases ranged from one hour to 30 years with a mean of 351 days. Diagnosis in the neonatal period was done in 37.7 % of cases, 69.7 % were diagnosed in the first 6 months and 83.9 % were diagnosed in the first year of life.

For all DS cases routine G- banding cytogenetic analysis was done and extended mosaic study was performed when indicated. Table (2) presents the cytogenetic data of the studied group.

 

Karyotype	No. of cases	Percentage
47,XY,+21	522	93.98
47,XX,+21	442
46,XY,der (13;21) (q10;q10),+21	2	3.5
46,XY,der (14;21) (q10;q10),+21	8
46,XX,der (14;21) (q10;q10),+21	7
46,XY,der (15;21) (q10;q10),+21	1
46,XY,der (21;21) (q10;q10),+21	13
46,XX,der (21;21) (q10;q10),+21	6
47,XX,+21 or 47,XY,+21/ 46,XX or 46,XY	22	1.84
Non-Classical Down syndrome	7	0.68
Total	1030	100

Table (2): Cytogenetic data of the DS cases

Translocation was present in 3.5 % of cases. All types of Robertsonian translocation were detected except t (21;22). Most of the cases had t (21; 21), which was present in 51.35 % of cases, followed by t (14; 21), which was present in 40.5 % of cases, t (13; 21) in 5.4 %, and t (15; 21) in 2.7 % of cases of translocation.

Non-classical karyotypes were present in 7 patients (0.68%), and included:

Non-classical karyotypes with sex chromosome abnormality:

Down syndrome and Turner syndrome:

46,X, +21 [5] / 46,XX [70]

46,XX der (21; 21)(q10; q10), +21[11] / 45,X [9]           

Down syndrome and Klienfelter syndrome:

-    47,XXY, der (21; 21)(q10; q10), +21

Non-classical karyotypes with marker  chromosome:

48,XY, + 21, + mar

47, XX, +21 [13] / 47, XX, +mar [6] / 46, XX [6]

47,XY, +21, t (4; 21) (q31.1; q22)

46,XY, der (21; 21)(q10; q10), +21 [16] / 46,XY [49]

      Males represented 54.13 % while females represented 45.87 % of the studied group. Table (3) shows the sex ratio in relation to cytogenetic data.

	Male (%)	Female (%)	Ratio
Non- disjunction	54.2	45.8	1.18
Translocation	63.9	36.1	1.7
Mosaic	45.5	54.5	0.8

Table (3): Sex ratio of the studied group

    Maternal and paternal ages in relation to the cytogenetic data was are represented in tables 4, 5 and 6.

	Mean (years)	Range (years)
Non - disjunction	31.8	16- 46
Translocation	24.5	18- 30
Mosaic	30	20.5- 39

 

Table (4): Mean maternal age in the studied group.

Age range (years)	Non-disjunction (%)	Translocation (%)
< 20	3.57	8.3
20-24	14.28	50
25-29	20.24	25
30-34	21.13	16.6
35 - 39	26.49	0
40 - 45	13.99	0
>45	1	0

Table (5): Maternal age range in non-disjunction and translocation cases.

	Mean (years)	Range (years)
Trisomy 21	36.93	19-62
Translocation	30.6	24-35

 

Table (6): Paternal age of the studied group

Family history of previously affected sib was positive in 3.18 % of cases and in close relative in 2.82% of cases. Family history of mentally retarded sib or close family member was found in 3.6% of cases. Most of the cases were first or second order of birth. Table 7 and 8 show referral causes in postnatally and prenatally referred cases.

 

Indication:	Percentage
Dysmorphic features	72.05
Mental retardation	12.15
Delayed physical milestones	7.9
Hypotonia	1.3
Congenital heart disease	1.65
Failure to thrive	2
Other reasons	2.95
Total	100

Table (7): Reasons of referral for cytogenetic study of postnatal cases.

Other causes of referral included prolonged neonatal jaundice, persistent fever, recurrent infections, obesity, hypothyroidism, dry skin, and delayed puberty.

 

Indication:	Percentage
Advanced maternal age	57.9
Positive triple test	31.58
Abnormal U/S	5.26
Previous DS	5.26
Total	100

Table (8): Reasons of referral for cytogenetic study of prenatal cases:

Discussion:

Down syndrome (DS) is perhaps the oldest condition associated with mental retardation and the most common genetic cause of developmental disability. It was the first chromosomal aberration described in man and the most frequent autosomal anomaly. The first clinical description of the disease appears to be Seguin’s, in 1846, under the name of furfuraceous idiocy (1). The English physician, John Langdon Haydon Down, wrote in 1866 the clinical description of the condition that was subsequently given his name. The term (mongol), (mongloid), and (mongolism) were widely adopted and used by professionals until about 30 years ago, when representatives of the Mongolian People Republic informally complained to the World Health Organization. Nowadays, DS is the preferred name (2).

In this paper we studied all cases referred as DS from January, 1996 to December, 2003. It was noticed that the number of DS cytogenetically confirmed cases is steadily increasing every year with an abrupt increase after 1999. The same is true for the number of falsely clinically suspected cases which started to increase after 1999, figure⁽¹⁾.

This may be attributed to the parallel increase in the governmental care and awareness of the handicapped children and those with special educational needs to the extent that DS phenotype became a phobia and many parents and physicians over react by referring normal babies for karyotyping to exclude DS.

On the other hand, this was not true for prenatal diagnosed cases, in which the number of cases was the same all through these years (only 1.56%). The same occurred in the first trimester screening and the triple test and is further confirmed by the very small percentage of prenatally diagnosed cases, reflecting an individual referral from special private sector.

Diagnosis in the neonatal period was done in 37.7 % of cases, 69.7 % were diagnosed in the first 6 months and 83.9 % were diagnosed in the first year of life. Early recognition of different kinds of chromosomal abnormalities in DS is important for proper genetic counseling. Against what is expected, most of the adult referred cases of DS in our study were not mosaics; instead, the cause of referral was premarital genetic counseling for his or her brother or sister or another member in the family.

Despite the expansion of prenatal screening programs, including both first and second trimester screening, we still have 98.3% of cases diagnosed postnatally, which reflects clearly the gap between the increased awareness of mental retardation and the preventive screening concept. In our study advanced maternal age was the most common reason for referral for prenatal diagnosis. In NDSCR, the reasons for prenatal referral have changed. In the early days of the NDSCR, maternal age was the major reason. But now most of the cases referred because of high risk maternal serum screening or specific ultrasound scans for nuchal fold or other ultrasound signs ⁽³⁾.

Prenatal detection rate of 1.7% versus 50% in developed countries makes it essential to reinforce the concept of preventive genetics in our population and to initiate a national policy targeting both health professionals and general publics to offer prenatal genetic screening for all pregnant ladies and prenatal diagnosis for screen positive cases. This needs an integrated system including diagnostic facilities, trained personnel and professional staff.

Many risk factors are suggested to cause DS. The only well established risk factor is advanced maternal age and so age –specific rates have been documented⁽⁴⁾. In our study, nearly 60% of mothers of non-disjunction cases were below 35 years. This is consistent with Astete et al., 1991 and Palka et al., 1990. In the latter study, the highest number of DS births was in the group of mothers between ages 25 and 29 years, this is in contrast to our finding in which the highest number of births was found in the group between 35-39 years. These findings are clearly related to the higher number of pregnancies in each age group^(5,6).

One study was found out that women who had a reduced ovarian complement (congenital absence or removal of an ovary) were at increased risk of having an infant with Down syndrome. This may suggest that the increased risk of Down syndrome with increased maternal age may be related to the physiological status of the ovaries or the eggs at this age⁽⁷⁾. Other potential explanations include delayed fertilization and changing hormone levels ⁽⁸⁾.

It was suggested that non-specific aging of ova predispose to meiotic defect. It was proposed that oocytes with greater number of chiasmata and the least predisposition to non-disjunction are formed earlier in embryogenesis and ovulated in early adult life. This causes increased rate of spontaneous abortion of aneuploid embryos and fetuses with advancing maternal age. Another hypothesis is the oocyte selection model, which states that a small number of aneuploid cells preexist in the germline that have arisen by mitotic non-disjunction during ovarian embryogenesis. Selection against the utilization of these aneuploid oocytes is exerted during each successive round of oocyte activation. Therefore, with time, older mothers gradually acquire a pool enriched with aneuploid oocytes⁽⁹⁾. More recently it was proposed that age-dependent susceptibility to chromosome 21 non-disjunction result from age-dependent loss of spindle forming ability(2). 

It was evident from our study that the mothers of translocation cases were younger than those of the non-disjunction cases. This is in agreement with the original finding from NDSCR which reported reduced maternal age in robertsonian translocation compared with the UK birth population ⁽¹⁰⁾.

In the case of mosaic DS the data was controversial. Richard, 1974 analyzed maternal age at the time of mosaic DS births and estimated that in 20% of cases, the extra chromosome arose through a mitotic non-disjunction in an euploid embryo soon after fertilization ⁽¹¹⁾. On the other hand, Pangalos et al., 1994, found that a meiotic error led to trisomy 21 in 10 out of 17 cases of mosaic DS. The mean maternal age was 31.4 years. A mitotic error was the most likely mechanism in the remaining cases, which had lower mean maternal age (27.4 years). This mitotic origin might support offering the same recurrence risk and genetic counseling as  full trisomy 21 ⁽¹²⁾.

Other maternal factors include higher socioeconomic status, which is due in part to maternal age ⁽¹³⁾. Mothers of Down syndrome children had more significant illnesses before conception, particularly psychological illness, and more medication ingestion in the year before conception. These remained statistically significant when adjusted for each other and for maternal age. Unfortunately, specific medications were not identified in this study ⁽¹⁴⁾. Families with histories of Alzheimer's disease are more likely to have Down syndrome offspring ⁽¹⁵). However, statistical power may have been lacking in most of them , and non of these factors were present in our study ⁽¹⁶⁾.

In our study only 7.1% of fathers were above 49 years. In spite of the fact that advanced paternal age (>49 years) has been associated with increased risk of DS births in a few studies ⁽¹⁷⁾, the risk has diminished with the appropriate adjustment for maternal age. Other studies documented that paternal age is not considered as a risk factor for conception of a child with DS ⁽¹⁸⁾.

Parental consanguinity was present in 12 % of cases which is much lower than the reported rate in general Egyptian population  (32-35%) ⁽¹⁹⁾.  It could be suggested that consanguinity has a little association with the incidence of DS and that the process of non-disjunction during oogenesis and spermatogenesis is rather a consequence of other causes particularly increased maternal age ⁽²⁰⁾.

On the other hand, Alfi et al., 1980 observed an increased frequency of consanguineous parents among their DS patients. They postulated the existence of a gene that could influence mitotic non-disjunction in the zygot, followed by the loss of monosomic cells and the formation of a complete trisomic or mosaic embryo ⁽²¹⁾. Authors suggested that the results of Alfi et al., based only on 20 cases could be influenced by some bias in selection, and were not confirmed by others who done their studies on much larger samples. Moreover, it is known that most of the free trisomies originate during the first meiotic division of the gamete, and this implies that the proportion of trisomic 21 produced by the action of such a gene , if it exists, would be very low ⁽²²⁾. 

It was documented that there is a significant excess of males among both the newborn children with DS and fetuses with DS aborted after prenatal diagnosis. Sex ratio in our study was as reported in other studies in all types of DS. In trisomy 21, about 54% are male fetuses or babies against the normal birth sex ratio of 51% male (3). However, in mosaics DS, the male to female ratio is 0.8 to 1 (10). This finding has subsequently been confirmed elsewhere , but remains unexplained ⁽²³⁾.

In our study, family history of previously affected pregnancy or in close relative was present in 6% of cases; all of them were in non-disjunction cases, which is a much higher figure than that obtained in NDSCR (1%). A number of recognized reasons were suggested as a cause of recurrence (3):

One parent may be mosaic trisomy 21. While this is rare it is a known cause for recurrence in young patients.

There may be some other rearrangements (not involving chromosome 21 translocations) present, which lead to imbalance during gametogenesis which is unproven yet.

There may be other genetic predisposing conditions leading to non-disjunction. This might be in the germ cells or in somatic cells. The occurrence of regular trisomy in a wider pedigree could support this theory.

Birth order showed a higher number of first and second borns. This is consistent with the study of jyothy et al., 2000 and Hay and Barbano, 1972. The latter suggested that the first-born infant is at higher risk independent on the maternal age^(24,25). On the other hand, Stoll et al., 1990, reported firstborns to be at lower risk of DS ⁽²⁶⁾.

Lejeune et al., 1959 was supported with the discovery of the chromosomal basis of DS ⁽²⁷⁾ . Shortly thereafter, Polani et al., 1960, discovered translocation DS in the daughter of a 21-year-old mother who was selected for study because the investigators had reasoned that some individuals may be affected through a separate, maternal-independent chromosomal mechanism ⁽²⁸⁾. The following year, Clark et al., 1961 reported mosaic DS, in a 2 year-old girl with physical stigmata of DS but near –normal intelligence ⁽²⁹⁾. It is well known that non-disjunction contributes to most cases of DS, followed by robertsonian translocation and mosaicism. Table 9 and 10 present a comparison of the cytogenetic data between our study and different published large international studies.

	No. of cases studied	Non- disjunction (%)	Translocation (%)	Mosa-ic  (%)	Non- classical (%)
Mutton et al., 1996 (10)	5737	95	4	1
Kovaleva et al., 1999 (30)	1778	90.7	5.7	3.6
Jyothy et al., 2000 (25)	1001	87.92	7.69	4.39
World Wide	17,738	92.9	4.3	2.2	0.5
Our study	1030	93.98	3.5	1.84	0.68

Table (9): Cytogenetic data published in several large studies of DS patients:

	Palliam and Huether, 1986	Our study
t (13;21)	0	5.4
t (14;21)	45.7	40.5
t (15;21)	2.9	2.7
t (21;21)	40	51.35
t (21;22)	2.9	0

Table (10): percentage of translocation cases in our study and that of Palliam and Huether, 1986 ⁽³¹⁾.

It is evident from the previous tables that we have more case of non- classical karyotype and t (21; 21) in our population. The origin of denovo t (21; 21) DS are usually different from the other reciprocal translocation. For the majority of such chromosomes are not centric fusion or whole arm exchange chromosomes, rather they are isochromosomes (iso 21q) resulting from fusion of sister chromatides ^(32,33). Whether isochromosomes arise during oogenesis is not established, and it is argued that isochromosomes arise post conception in somatic tissues of trisomic conceptus ^{(34) .} The relation of this theory to our findings could not be explained and needs further research.

We concluded that, in Egypt with 1.6 million births / year and estimated risk of 2285 DS births annually, the concept of preventive genetics should be reinforced with a national policy targeting both health professionals and general publics to offer prenatal genetic screening for all pregnant ladies and prenatal diagnosis for screen positive cases. This needs an integrated system including proper  diagnostic facilities, trained personnel and professional staff.

References:

1- DeGrouchy J and Turleau C. Clinical atlas of human chromosomes. Wiley medical publication. John Wiley and sons. New York, Toronto. 2^nd ed. 1983. pp70.

2- Tomlie JL. Down syndrome and other autosomal trisomies. In: Emery and Rimoin’s principles and practice of medical genetics. Rimion DL, Conner JM, Pyeritz RE. 3^rd ed. 1996; ch 47: pp 925-971.

3- NDSCR: National Down Syndrome Cytogenetic Register. Wolfson Institute of Preventive Medicine. Barts and the London School of Medicine and Dentistry. Charterhouse Square. London 6BQ.

4- Hechet Hecht CA, Hook EB. Rates of Down syndrome at live birth by one-year maternal age intervals in studies with apparent close to complete ascertainment in populations of European origin: A proposed revised rate schedule for use in genetic and prenatal screening. Am J Med Genet 1996; 62:376-385.

5- Astete C, Youlton R, Castillo S, Be C, Daher V. Clinical and cytogenetic analysis of 257 cases of Down’s syndrome. Rev. Chil Pediatr 1991; 62:99-102.

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