Genetics and Prenatal Diagnosis in Pediatric Surgery

Serious malformations occur in 1.5% of all births. For half of these children the etiology is unknown; the other half have a documented genetic or teratogenic cause. The importance of prenatal diagnosis lies in its ability to give parents several options. If there are malformations or conditions incompatible with life, the pregnancy can be terminated. If the malformation is correctable at term, surgery can take place after delivery. For some malformations, progressive adverse effects in utero may warrant consideration of early delivery or fetal surgery.

Modern obstetric care includes close monitoring during pregnancy and various prenatal screening-tests, such as alpha-fetoprotein screening and prenatal ultrasonography. Fetal ultrasonography is routinely performed around the 18th gestational week. Occasionally, there are indications for more invasive screening tests, such as chorionic villus sampling, amniocentesis, fetoscopy, fetal sampling, and percutaneous umbilical blood sampling.

Early detection of congenital defects in utero allows for both parental counseling and referral to a perinatal center where further investigation of the condition can be undertaken and monitoring of the high-risk pregnancy can be done. The perinatal center should advise when, where and how delivery will take place. Appropriate centers must have a skilled neonatal intensive care facility and pediatric surgical expertise.

Prenatal Diagnostic Studies and Tests

Chorionic Villus Sampling (CVS)

CVS allows biopsy of fetal cells for chromosomal, enzymatic or DNA analysis in the first trimester (9-12 weeks gestation). Cells are obtained by direct biopsy of chorion, either transcervically or transabdominally, preferably under ultrasound guidance The major disadvantage of this procedure is the associated 3% increased rate of spontaneous abortion. CVS is the preferred prenatal diagnostic test for many high risk conditions (i.e., cystic fibrosis, sickle cell disease, Duchenne’s dystrophy, etc.)

Alpha-Fetoprotein (AFP) Screening

AFP is one of the major proteins in fetal serum. Screening should be offered to women at 16-18 weeks of gestation. AFP in maternal serum is of fetal origin. Increased levels of AFP are found in fetuses with neural tube defects, anencephaly, Turner’s syndrome, omphalocele, sacrococcygeal teratoma, intestinal obstruction and missed abortion. Low AFP levels are observed in intrauterine growth retardation, Trisomy 18, Trisomy 21, and other conditions. However, a normal AFP level does not rule out trisomy. Women with a maternal age exceeding 35 years are at high risk for having babies with Downs Syndrome. Consequently, this group and indeed most pregnant women are now offered assay for both AFP and human chorionic gonadotropin (hCG). Human chorionic gonadotropin levels are frequently elevated in fetuses with Trisomy 21.

Amniocentesis

Amniocentesis involves sampling and analysis of amniotic fluid to detect presence of metabolic disorders and chromosomal defects. Amniocentesis can be safely performed between 12-18 weeks gestation and usually takes 14 days to obtain results. The safety of this procedure is somewhat better than CVS. The risk of miscarriage following amniocentesis is less than 1%.

Fetoscopy and Fetal Sampling

When appropriate, these procedures are performed between 15 and 21 weeks of gestation. Analysis of fetal blood can reveal many conditions including Wiskott-Aldrich syndrome, hemophilia A and B, hemoglobinopathies, alpha 1-antitrypsin deficiency, and chronic granulomatous disease. Conditions in which the genetic defect is not expressed in the amniotic fluid can be discovered by sampling from the skin and liver. Fibroblastic cell culture can be performed to reveal mosaicism. The risk of miscarriage is around 5%.

Percutaneous Umbilical Blood Sampling

Percutaneous aspiration of umbilical cord blood can be safely performed under ultrasound guidance. The blood samples can reveal hematologic abnormalities including isoimmunization. This procedure is usually done between 18 and 20 weeks of gestation. The risk of miscarriage is about 2%. Results of analysis are usually available within 2-3 days.

Prenatal Ultrasound

Sonography is the most important method of fetal screening. It is useful to determine gestational age of the fetus, single or multiple births, the amniotic fluid volume, growth in high risk pregnancies, and a significant number of fetal anomalies. Ultrasonography is the best noninvasive method for determining both functional and anatomic abnormalities in the fetus. Evaluation of amniotic fluid volume is most important. When performed in the 4th month of gestation, the finding of normal amounts of amniotic fluid suggests normal swallowing and renal function. A finding of reduced amniotic fluid volume, or no fluid at all, is a sign of impaired renal function, such as obstruction, multicystic kidneys or renal agenesis. Too much amniotic fluid (more than 2000 ml = polyhydramnios) suggests impaired fetal swallowing (neurologic abnormality, anencephali), proximal alimentary tract obstruction, or compression of the esophagus due to diaphragmatic hernia or congenital lung malformation.

Although a single ultrasound study can provide a wealth of information, serial studies over time can provide even more. Functional evaluation of kidney, heart, and lungs is considerably more accurate with repeated exams.

The heart and the great vessels are easily visualized with ultrasonography or fetal echocardiography. The dynamic function can be evaluated. The four chambers and the two great vessels should be visualized and allows the diagnosis of anomalies such as tetralogy of Fallot, tricuspid atresia, hypoplastic left heart, aortic valve stenosis/ atresia and double outlet right ventricle.

Cerebral malformations, encephaloceles, and hydrocephalus are readily identified by prenatal ultrasound. Intraabdominal structures like hepatic neoplasms (hemangioma), neuroblastoma, enteric duplications and atresias of the gut can also be detected. The differentiation of omphalocele and gastroschisis is especially important because the prognosis in omphalocele is so much worse, compared to gastroschisis, because of the serious associated anomalies and chromosomal defects.

Indications for Prenatal Diagnosis

General Risk Factors

Maternal age more than 35 years (increased risk for fetal chromosomal abnormality). Elevated or reduced serum AFP Increased serum hCG.

Specific Risk Factors

Previous still birth or neonatal death. Previous child with a structural defect or chromosomal abnormality. Structural abnormality in any of the parents. Balanced translocation in any of the parents. Inherited disorders (i.e., cystic fibrosis, metabolic disorders, sex-linked disorders) Medical disease in the mother (i.e., diabetes mellitus) Exposure to teratogens (i.e., ionizing radiation, anticonvulsant medicine, alcohol, etc.) Infections (i.e., rubella, toxoplasmosis, cytomegalovirus)

Treatment of the Fetus

Hydrops fetalis can occur secondary to isoimmunization induced hemolysis. Prenatal treatment of this condition may include erythrocyte transfusion in utero. Transplacental treatment can be administered for cardiac arrhythmias (especially supraventricular tachycardia) leading to hydrops. The most common prenatal treatment used for the fetus is steroid (i.e., glucocorticoid ) administration to increase pulmonary surfactant in the lungs of the preterm infants.

Fetal Surgery

The indication for fetal surgery is malformations that interfere with fetal organ development, which if alleviated would allow normal organogenesis. Pioneering work is now carried out in a few centers for highly selected cases; however, these procedures involve significant risks for both the mother and the fetus (i.e., infection, premature labor, etc.).


Although no large series have proven any long term benefits, work continues (and should continue at a few centers with close supervision) on the use of fetal surgery for:

1. vesicoamniotic shunt for severe bilateral hydronephrosis with pulmonary hypoplasia
2. congenital diaphragmatic hernia with prenatal prosthetic patch repair or tracheal plugging
3. lobectomy for congenital cystic adenomatoid malformation
4. thoracoamniotic shunt for fetal chylothorax
5. ventriculoamniotic shunt for severe obstructive hydrocephalus
6. resection of sacrococcygeal teratoma to prevent cardiac failure secondary to arteriovenous fistula
7. correction of critical aortic stenosis to prevent severe left ventricular hypoplasia

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Anemia

Unlike many Chapters of this handbook that deal with a specific surgical condition, this short Chapter touches on a physiologic state that has great importance to the surgeon. Anemia denotes a state in which a patient has less than normal hemoglobin. In this situation, decreased oxygen transport may decrease wound healing, may increase cardiac stress during or after surgical event, and may predispose to a variety of postoperative complications. Fortunately, all these anemia problems are less likely in the pediatric patient, but still one must consider carefully the presence of anemia, its probable cause, whether it should be corrected (how and how quickly), and its chance of seriously affecting surgical outcome.

Definition

Generally, anemia is defined as hemoglobin less than 10 grams/deciliter. The normal value for adults and older children is 12-16 grams/deciliter. However, this value may be higher in the newborn and will characteristically fall below this normal range during the first 1-2 months of life.

Physiologic Anemia

Babies rapidly lower their hemoglobin in the neonatal period. Values often fall to the 9-10 g/dl level with corresponding hematocrits of 25-30%. This change is normal and reflects a slow initiation of hematopoesis by the neonatal bone marrow. If surgery is necessary during this period, the surgical and anesthesiological staff must decide whether the transfusion of blood outweighs risks of transfusion and delay of hematopoesis onset.

Iron Deficiency

Iron supplies are transferred to a neonate late in intrauterine life. These supplies may be low in preterm children, just as the supply of other nutrients, vitamins, minerals are low in early children. If there is no compelling reason to correct the anemia quickly, the infant is given iron orally. This is absorbed in the duodenum and proximal jejunum and nicely corrects the problem. Parental iron or transfusion are the alternatives if this deficiency must be corrected quickly.

Hereditary Spherocytosis

This is an autosomal dominant disease process that prevents red cells from assuming their characteristic biconcave shape. The elliptical red blood cells do not move easily through the capillary bed or the pulp of the spleen. Red cells thus entrapped are more rapidly destroyed, resulting in splenomegaly, jaundice, and anemia. The presence of a family history consistent with this disease and the observation of spherocytes and reticulocytes on a peripheral blood smear confirm the diagnosis. Further confirmation involves demonstration of increased cellular fragility in the osmotic fragility test. These children are highly prone to the development of gallstones and concomitant biliary tract disease. Thus, they need full evaluation of those structures if they are coming to splenectomy to control the spherocytosis.

Sickle Cell Anemia

This is the most common inherited disorder of the African American population. Up to 10% of this population is affected. This disease is an autosomal recessive trait and requires the homozygous state for expression of the full-blown disease. Most of these patients have anemia, leukocytosis, jaundice, and perhaps splenomegaly early. By teenage years, the spleen usually shrinks from progressive infarction and fibrosis. However, these children by then often also have biliary stones and biliary tract disease.

In severe forms of this disease, children have painful crises that involve bone pain, severe right and left upper abdominal pain, strokes, and pulmonary infarctions. Many of these children develop osteomyelitis and leg ulcers.

A peripheral smear demonstrates sickle shaped red blood cells, especially when crisis is occurring. However, today most of these children are quickly diagnosed at the time of birth through mandated state screening programs. Hemoglobin electrophoresis confirms the presence of hemoglobin S and indicates the zygosity. Prenatal diagnosis is possible through amniocentesis and DNA analysis.

Although surgeons are not generally asked to manage children with this disease, they are frequently asked to consult for abdominal pain. When surgery is necessary for appendicitis, biliary problems, etc., it is important that the surgeon know how to manage these children to optimize outcome. Preoperative suppressive transfusions, exchange transfusions, meticulous hydration and prevention of hypoxia all are important aspects of preoperative, intraoperative, and postoperative care.

Other Anemias

Diverse other anemic states more rarely come to the attention of pediatric surgeons. Generally, the request is to assist with a complication of the anemia, most often splenomegaly or biliary complications such as cholelithiasis. Care should be used to correct the anemia to the degree possible before operation. If this is not possible, the surgeon must try to optimize care to prevent postoperative complications associated with low red blood volume and decreased oxygen transport.

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Immediate Postoperative Care

The postoperative care of surgical neonates and children begins upon completion of wound closure. The level of postoperative care administered is dependent upon the procedure performed but some general guidelines are provided below. Specific guidelines for postoperative management of many pediatric surgical conditions are provided throughout this handbook.

Wound and Dressing Care

Prior to the removal of the sterile surgical drapes, the skin surrounding the surgical wound is cleansed with warm saline-soaked sponges or lap pads to remove any debris, blood, or prep solutions surrounding the wound. The area is gently padded dry and a sterile towel or dressing is placed over the wound to prevent contamination at the time of drape removal. The type of dressing applied to surgical wounds is selected according to surgeon preference, the type of wound created, and the method of closure. For clean procedures, a dry, sterile dressing (i.e., gauze, steristrips, Opsite®, Tegrederm®) is suitable. Antibiotic ointments and other wound applicants are generally not necessary. To minimize the stress and pain of later dressing removal, dressings are secured in position with the minimal amount of tape or occlusive barrier that achieves coverage of the wound.

Extubation and Transfer

Intraoperative monitoring devices should be left in place until after extubation. A physician member of the surgical team should be present at the time of extubation and assist in the transfer of the pediatric surgical patient to the postanesthesia care unit or appropriate intensive care unit. If respiratory rate or inspiratory tidal volumes are inadequate, the child should be observed in the OR until breathing has improved. Special attention to body temperature and measures to prevent hypothermia after drape removal should be instituted including infrared heating lights, wrapping with warm blankets, and increasing the ambient room temperature.

Postoperative Orders

The postoperative orders are individualized for each patient. In general, outpatient procedures will require only simple postoperative care and specific wound care instructions for the parents. Arrangements for office follow-up visits are discussed. A general outline for writing postoperative orders in postsurgical pediatric patients is provided below.

Admission Order

Specific information regarding the type of bed and/or location within the hospital to which the patient goes after recovery is listed. Arrangements for intensive care unit beds are made preoperatively. If observation status or discharge from the recovery unit is desired, specific instructions regarding wounds, medications, and anticipated clinical course/problems are provided to the parents or primary caregiver.
Attending Physician and Consultants

List the attending physician and all consultants who will participate in the care of the patient. In addition, one specifies which physician(s) and/or service(s) will be the primary providers of postoperative care and orders. The nursing staff must be clearly informed regarding who is contacted for questions about care and for any problems that arise.
Diagnosis

List the primary diagnosis and/or the procedure that has been performed.
Allergies

List any known drug allergies or other sensitivities (i.e., latex, tape, antibiotics, pain medications, etc.)

Admission Weight

The patient’s preoperative weight is specified. This is the weight that is used to calculate medication dosages, fluids, nutritional requirements, etc.

Vital Signs

Provide instructions for the frequency at which vital signs are monitored and recorded. Parameters for changes in vital signs that require notification of the surgical team are clearly specified.

Monitoring Equipment

List any special monitoring devices that are appropriate for postoperative care including pulse oximetry, apnea and/or cardiac monitors, etc.

Ventilator Settings and Respiratory Care

For patients requiring postoperative ventilatory support, specific instructions regarding ventilator mode, tidal volume, peak inspiratory pressure, inspired oxygen concentration, etc. are provided. If other respiratory interventions (i.e., nebulizers, chest physiotherapy, frequent suctioning) are required, specific written orders are made.

Intravenous Fluids

Maintenance and replacement fluid orders are provided.

Diet

Special diets (i.e., clear liquids, general diet) or oral restriction (i.e., NPO) are specified, including orders for initiation of enteral tube feedings when applicable.

Activity

Level of activity and/or restriction (i.e., bedrest, ambulation, etc.) is specified. Physical therapy may be helpful to some hospitalized patients and is initiated when appropriate.

Medications

All medications including doses, routes of administration, and frequencies of administration are recorded clearly and accurately. Analgesic and antiemetic medications are ordered when appropriate. Doses are calculated on a per weight basis.

Wound Care

Special instructions for dressing care or surgical wounds are provided when applicable.

Drains

Drain care orders include specific requests for suction, stripping, frequency of emptying, and quantification of output. Nasogastric tubes are placed to suction or gravity drainage according to attending surgeon preference. Foley catheters are placed to gravity drainage.

Special Studies

Any radiographic exams or follow-up studies are specified, and the radiology department and/or attending radiologist should be notified of all requests. Chest radiographs are obtained in the recovery room or intensive care unit for all patients who remain intubated or who had intraoperative placement of central venous lines or catheters.

Laboratory Tests

Routine laboratory testing is often not necessary in pediatric surgical patients, especially those who have procedures in the surgicenter and are discharged shortly after surgery. Specific laboratory studies are obtained if the results are expected to alter clinical management of the patient. Laboratory tests are often indicated in children who undergo extensive and complicated procedures.

Pain Management

Achieving adequate pain relief is important in children, although children often do not or cannot complain specifically of pain. Pain may adversely affect recovery of infants since painful stimuli may result in decreased arterial saturation and increased pulmonary vascular resistance. Effective pain control allows earlier ambulation and faster recovery in older children.

Local anesthetics administered in the operating room can provide prolonged pain control. Local wound infiltration or regional nerve blocks with bupivicaine (Sensorcaine®) provide pain control for 4-6 hours following an operation. The maximum dose is 3 mg/kg given as a 0.25–0.75% solution.

For larger operations, intravenous narcotics provide excellent pain control. Liberal use of patient controlled analgesia devices and epidural catheters improve postoperative pain control after many abdominal or thoracic operations.

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Preoperative Care

Consultation

Prior to surgery for any patient, surgical consultation occurs. This provides a meeting and introduction between child and surgeon and proceeds to a complete history and physical examination. Since many children meet a surgeon for the first time on referral, the results of a prior history and physical examination are often available. If that is the case the previous findings are reviewed, verified, and further information is sought that may elucidate the diagnosis.

The meeting may be brief but creates the foundation for further interaction between surgeon and child. It is certainly an opportunity for the surgeon to create a friendship, or at least trust, between a frightened child and the person who will ultimately perform surgery. This meeting also is the chance to create communication and trust with anxious parents. Consequently, child and parents must be given adequate opportunity to present their understanding of the diagnosis, raise questions concerning surgery and in-hospital care, and discuss worrisome questions such as pain control, postoperative management, ultimate outcome and long-term results.

If a crowded clinic schedule precludes adequate time to cover all aspects of anticipated surgery, it is quite appropriate to schedule further visits or simply to arrange time for phone conferences with all concerned. Frequently, the surgeon can include other significant family members (grandparents, aunts, and uncles, siblings) by arranging for evening phone conversations.

Since many presurgical patients have already undergone diagnostic testing, it is important to review these tests and share the surgeon’s interpretation with the child and family. Sometimes this entails consultation with other specialists at the children’s hospital (radiologist, pathologists, and pediatric subspecialists). The results of these consultations will generally not be available at the time of the surgical consultation, but the results or discussion can easily be shared with child and family members via phone, e-mail, or fax. Communication at present is one of the easier, but most important, aspects of patient care.

Physical Examination

Abnormal findings on physical examination are often reported to a surgeon prior to the patient encounter. This does not preclude another examination at the time of the consultation visit. Additional findings may be demonstrated, and certainly one wishes to confirm the previously reported findings. Such simple matters as hernias or hydroceles are often confused and need the careful reexamination of the pediatric
surgeon to clarify. In addition, associated findings, well known to the pediatric surgeon, may not be common knowledge to the referring pediatrician or family practitioner. Therefore, a good physical examination is always advisable prior to surgical intervention.

Diagnostic Studies and Laboratory Investigations

The need for diagnostic studies varies from none to extensive. In the case of a child with a reducible inguinal hernia, a good, but simple, physical examination constitutes the best diagnostic study. Further tests, radiographs, blood examinations, etc. are invasive, bothersome, expensive and unwarranted unless there are other findings or complaints. However, the child who presents with severe, recurrent abdominal pain without any physical findings may need extensive studies to demonstrate the causative pathology (or lack thereof). Suffice to say, diagnostic studies are chosen and done that are needed to completely and safely make a diagnosis and sufficient to advise a child and family concerning the need for surgical intervention.

It is clear that a healthy child on a standard diet requires nothing as far as preoperative testing if the surgical problem is simple, can be done under outpatient general anesthetic without hospital stay. For example, a two-year-old child with uncomplicated bilateral inguinal hernias, eating until a few hours before surgery, whose cheeks and lips betray no sign of anemia can and should undergo operative repair without diagnostic testing. Careful questioning of the family history adequately excludes inherited diseases and bleeding dyscrasias. Examination of the child provides all the further information needed to make a correct decision concerning the need for further tests. In contrast, a two-year-old child with previous diagnosis of biliary atresia with unsuccessful Kasai procedure and progressive biliary cirrhosis clearly needs a very complicated and extensive diagnostic evaluation to allow a determination as to whether he can undergo hepatic transplantation.

In summary, the diagnostic regimen is designed to be sufficiently brief or thorough to correctly and adequately identify the surgical problem(s) and formulate the best and safest surgical plan.

Pain Management

One of the greatest concerns for child or parents when approaching a surgical event is the problem of postoperative pain control. Most children are not particularly concerned about the technical details of the surgery they will undergo, but they are greatly fearful of the pain that they endure in the postoperative period. Knowledge that this can be controlled in a variety of ways provides some comfort. Knowledge that they will also be in the company of their parents during this period of time is also vitally important.

Consequently, the consultation visit or phone conferences include a thorough discussion of postoperative pain management. Commonly used methods of pain control include intraoperative local anesthetic administration, intravenous narcotics, patient controlled analgesia, caudal blocks, epidural blocks and continuous epidural anesthesia. Although these can all be discussed before the surgical event, it is generally best to provide at least one to two hours in the preanesthetic room so this can be discussed a second time with the anesthesia staff. This is the time of the final decision concerning the exact pain control methods to be used. Since this is often tailored to fit the anesthesia used during the operative event, the anesthesiologist is included in this decision.


Blood Donation

Due to the tremendous information on the hazards of blood transfusion, most parents want to discuss possible transfusion thoroughly. Since transfusion is a rare event, discussion can be limited to acknowledgement that transfusion is most unlikely, and so much so that blood is not routinely prepared for the operation anticipated. In the event that transfusion is a possibility, discussion centers on the use of banked blood versus donor directed blood. This is both a controversial and emotional subject so it is sometimes necessary to involve the director of the blood bank service to fully elucidate the questions posed. Parents must fully understand that blood samples will be necessary from child and donors prior to the surgical date. Furthermore, they need to fully understand that all donor directed blood is subjected to the same testing required for all other blood donations. Finally, parents need to understand that type match does not necessarily predict cross match and that fulfillment of all these requirements requires adequate time before the surgery date.

Presurgical Visitation and Teaching

Most children’s hospitals provide a presurgical visitation and teaching program. These programs allow children to visit all portions of the operative suite prior to surgery. They become familiar with the holding area, the operating room, and the postanesthesia recovery area. They have an opportunity to try on “scrubs”, gowns, masks and caps. The nurses from the various areas answer questions, reassure the children of their parent’s nearness and participation in the entire process, and particularly address concerns about postoperative pain. In our particular hospital, the children conclude the visit by making a mural that is taped to the entry hall wall. As the children pass to the operating rooms, they can look for their previous artwork. We hope it lessens their anxiety and certainly endorse the use of these programs if available.

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