SGA and IUGR

SGA and IUGR
By Tina Burleson Stewart, MD

What is the difference between SGA and IUGR?
Can these terms be used interchangeably?
SGA - small for gestational age infants
* an infant whose weight is lower than the population norms
* defined as weight below 10th percentile for gestational age or greater than 2 standard deviations below the mean
* cause may be pathologic or nonpathologic

IUGR - intrauterine growth retardation
* defined as failure of normal fetal growth
* caused by multiple adverse effects on fetus
* due to process that inhibits normal growth potential of fetus


So what is the difference between SGA and IUGR?
* These terms are related but not synonomous.
* Not all IUGR infants are small enough to fit the qualifications for SGA.
* Not all SGA infants are small because of a growth-restrictive process, and therefore, do not meet criteria for IUGR.

Incidence
* 3-10% of all pregnancies
* 20% of stillborn infants
* perinatal mortality 4-8 times higher
* half have serious or long-term morbidity

Epidemiology
* more common in low socioeconomic class
* more common in those of African-American race
* leading cause in third world countries is inadequate nutrition of mother
* leading cause in US is uteroplacental insufficieny

Causes of IUGR
* maternal factors
* fetal factors
* placental factors
* environmental factors

Maternal causes of IUGR
* inadequate nutrition of mother
* multiple gestation
* uteroplacental insufficiency
* hypoxia
* drugs

Mother’s Malnutrition
* lack of adequate food supply
* poor weight gain
* chronic illness
* malabsorption

Multiple Gestation
* difficult to provide optimal nutrition for greater than one fetus
* uterine capacity limitations

Uteroplacental Insufficiency
* preeclampsia
* chronic HTN
* renovascular disease
* vasculopathy from diabetes
* drugs

Hypoxia
* maternal hemoglobinopathies - sickle cell
* maternal anemia
* maternal cyanotic heart disease
* mom living at high altitudes

Maternal Drug Use and Toxin Exposure
* cigarettes
* cocaine
* amphetamines
* antimetabolites - MTX
* bromides
* heroin
* hydantoin
* isoretinoin (Accutane)
* methadone
* alcohol
* methyl mercury
* phencyclidine
* phenytoin (Dilantin)
* polychlorinated biphenyls
* propanolol
* steroids - prednisone
* toluene
* trimethadione
* warfarin (Coumadin)

Fetal Causes of IUGR
* genetics
* congenital infection
* inborn errors of metabolism

Chromosome Disorders associated with IUGR

* trisomies 8, 13, 18, 21
* 4p- syndrome
* 5p syndrome
* 13q, 18p, 18q syndromes
* triploidy
* XO - Turner’s syndrome
* XXY, XXXY, XXXXY
* XXXXX

Syndromes associated with low birth weight
* Aarskog-Scott syndrome
* anencephaly
* Bloom syndrome
* Cornelia de Lange syndrome
* Dubowitz syndrome
* Dwarfism (achondrogenesis, achondroplasia)
* Ellis-van Creveld syndrome
* Familial dysautonomia
* Fanconi pancytopenia
* Hallerman-Streiff syndrome
* Meckel-Gruber syndrome
* Microcephaly
* Mobius syndrome
* Multiple congenital anomalads
* Osteogenesis imperfecta
* Potter syndrome
* Prader-Willi syndrome
* Progeria
* Prune-belly syndrome
* Radial aplasia; thrombocytopenia
* Robert syndrome
* Robinow syndrome
* Rubinstein-Taybi syndrome
* Silver syndrome
* Seckel syndrome
* Smith-Lemli-Opitz syndrome
* VATER and VACTERL
* Williams syndrome

Congenital Infections associated with IUGR
* rubella
* cytomegalovirus
* toxoplasmosis
* herpes
* syphilis
* varicella
* hepatitis B
* coxsackie
* Epstein-Barr
* parvovirus
* Chagas disease
* malaria

Metabolic disorders associated with low birth weight
* agenesis of pancreas
* congenital absence of islets of Langerhans
* congenital lipodystrophy
* galactosemia
* generalized gangliosidosis type I
* hypophosphatasia
* I cell disease
* leprechaunism
* maternal and fetal phenylketonuria
* maternal renal insufficiency
* maternal Gaucher disease
* Menke syndrome
* transient neonatal diabetes mellitus

Placental Causes of IUGR
* placental insufficency
o very important in the 3rd trimester
* anatomic problems
o infarcts
o aberrant cord insertions
o umbilical vascular thrombosis
o hemangiomas
o premature placental separation
o double vessel cord
* microscopic changes
o villous necrosis
o fibrinosis

Environmental Causes of IUGR
* high altitude - lower environmental oxygen saturation
* toxins

IUGR classification
* SYMMETRIC
* height, weight, head circ proportional
* early pregnancy insult: commonly due to congenital infection, genetic disorder, or extrinsic factors
* normal ponderal index
* low risk of perinatal asphyxia
* low risk of hypoglycemia
* ASYMMETRIC
* head=height, both > weight
* brain growth spared
* later in pregnancy: commonly due to uteroplacental insufficiency, maternal malnutrition, hypoxia, or extrinsic factors
* low ponderal index
* increased risk of asphyxia
* increased risk of hypoglycemia

Ponderal Index
* The ponderal index is used determine those infants whose soft tissue mass is below normal for their stage of skeletal development. Those who have a ponderal index below the 10th % can be classified as SGA.
* Ponderal Index = birth weight x 100 crown-heel length

Diagnosis
Prior to delivery, it is necessary to determine the correct gestational age.
* last menstrual period - most precise
* size of uterus
* time of quickening (detection of fetal movements)
* early ultrasound - the earlier the better accuracy
o biparietal diameter
o abdominal circumference - best sensitivity
o ratio of head to abdominal circumference
o femur length
o placental morphology and amniotic fluid

Diagnosis after delivery (OUR JOB!)
* low birth weight - this parameter alone misses big IUGR infants and overdiagnoses constitutionally small infants
* appearance - thin with loose, peeling skin; scaphoid abdomen; disproportionately large head; may be dysmorphic
* ponderal index
* Ballard/Dubowitz - accurate within 2 weeks of gestation if birth weight >999g, most accurate within 30-42 hrs of age
* birth/weight curves

Complications
* hypoxia
o perinatal asphyxia
o PPHN
* hematologic - polycythemia
* meconium aspiration
* metabolic
o hypoglycemia
o hypocalcemia
o acidosis
* hypothermia
* neurological
o more tremulous
o more easily startled
o less visual fixation
o less activity
o less oriented to visual and auditory stimuli

Management in utero
* serologic testing if desired by parents
* decrease mother’s activity
* stop or decrease risk factors if possible
* closely monitor with biophysical profile or nonstress testing or amniotic fluid measurements
* ultrasound every 10-21 days
* teach mom fetal kick counting
* deliver if reaches 36 weeks

Management after birth
* obtain history of risk factors
* appropriate resuscitation
* prevent heat loss
* watch for hypoglycemia
o check glucoses
o early feeding
o parenteral dextrose
* check hematocrit
* screen for congenital infections
* screen for genetic abnormalities
* check calcium

Outcome

* depends on cause of IUGR/SGA and neonatal course
* symmetric IUGR - poor outcome because early insult
* asymmetric IUGR - better outcome because brain spared
* very bad if brain growth failure starts at < 26 weeks
* school performance influenced by social class
* 25-50% likelihood of neurodevelopmental problems


SGA and IUGR.ppt

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Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz Syndrome (SLOS)
By: Suraj Gathani

Description and Occurrence
* Autosomal recessive disorder
o Cholesterol metabolism effected.
* Common characteristics:
o Multiple malformations at birth.
o Mental retardation later.
* Occurrence:
o 1 in 20,000 people of central European decedents.
o Rare in Africans and Asians.

Clinical Features
* Clinical anomalies:
o Mental retardation (100% affected)
o Small brain at birth (microcephaly) >90%
o Second and third toe fusion (synadactyly) ~98%
o Genital abnormalities in males >50%
o Muscle weakness (hypotonia) ~50%
o Polydactyly
o Abnormalities of heart, lung, kidneys, and liver.

Smith-Lemli-Opitz Syndrome
* Distinctive facial features:
o High, broad forehead
o Narrow temples
o Upward pointing nostrils
o Drooping eyelids and a broad nasal bridge
* Behavioral characteristics:
o Repeated self injury
o Prolonged temper tantrums & violent outbursts
o Hyperactivity

Molecular Defects
* Caused from mutation in the DHCR7 gene
o Located at 11q12-13
o Encodes for sterol-Δ7-reductase
* Defects in sterol-Δ7-reductase
o Build up of 7-dehydrocholesterol
o Deficiency of cholesterol
* Importance of cholesterol
o Important component in cell membrane and myelin sheaths
o Precursor for steroid hormones such as progesterone
o Precursor for bile salts

Cholesterol Metabolism
Diagnosis and Treatment
* Diagnosis:
o Detection of an elevated level of 7-dehydrocholesterol in plasma
* Treatment:
o Individuals with SLOS need support and care
o Congenital abnormalities can be corrected with surgery.
o Dietary cholesterol supplementation is beneficial.

Reference

Smith-Lemli-Opitz Syndrome.ppt

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Management Considerations for Patients on Anticoagulants

Management Considerations for Patients on Anticoagulants

Dental Management of Patients on Anticoagulant and Antiplatelet Drugs
By:Donald A. Falace, DMD
Professor and Division Chief
Oral Diagnosis and Oral Medicine
University of Kentucky College of Dentistry


Normal Hemostasis

Following injury to a blood vessel:
* Vascular retraction (vasoconstriction) to slow blood loss

2. Adherence of platelets to the vessel wall (endothelium) and then to each other to form a platelet plug

3. Initiation of the coagulation cascade resulting in the formation and deposition of fibrin to form a clot

Coagulation Cascade
* Extrinsic pathway: Factor VII is activated by tissue factor (phospholipid) that is released by injured perivascular or vascular tissues; very rapid reaction
* Intrinsic pathway: Factor XII is activated by exposure to collagen from vessel wall (endothelium) or blood cell membrane; slower reaction

* Anticoagulants:
o Inhibit the production of clotting factors
* Antiplatelet Agents:
o Interfere with the functioning of platelets, thus inhibiting platelet aggregation

Anticoagulants
Coumarin Derivitives (dicoumarol, warfarin: Coumadin, Panwarfin)
Coumadin antagonizes the production of vitamin K
Vitamin K is necessary for the synthesis of four of the coagulation factors (VII, IX, X and prothrombin)

Pharmacologic Properties (warfarin: Coumadin)
* Taken orally
* Metabolized in the liver
* Half-life: 1.5-2.5 days
* Duration of action: 2-5 days (it takes several days for dosage changes to take effect)
* Increased anticoagulant effect when combined with:
o Antibiotics
o Aspirin
o NSAIDs
o Antifungals
o Tramadol
o Tricyclic antidepressants
o Certain herbals (gingko, ginsing, ginger, garlic)

Co-morbid Conditions That Can Contribute to Increased Bleeding
* Liver disease
* Kidney disease
* Tumor
* Bone marrow failure
* Chemotherapy
* Autoimmune diseases

Conditions for which Coumadin is prescribed to prevent unwanted blood clotting
* Prophylaxis/Treatment of:
o Venous thrombosis (DVT)
o Pulmonary embolism
o Atrial fibrillation
o Myocardial infarction
o Mechanical prosthetic heart valves
o Recurrent systemic embolism

Laboratory Tests to Monitor the Activity of Coumadin
* Prothrombin Time (PT): time for fibrin formation via the extrinsic pathway-factor VII
o Test performed by taking a sample of the Pt’s blood and adding a reagent (thromboplastin) and calculating the time required to form a clot; expressed in seconds
* PT Ratio: Pt’s PT/Normal PT
* Normal PT ration = 1
* Problem: There is variation among thromboplastin reagents, therefore the results from lab to lab are not comparable

Same patient- Same blood
5 different laboratories - 5 different PT Ratios!
Solution: International Normalized Ratio (INR)
o A mathematical “correction” that corrects for the differences in the sensitivity of thromboplastin reagents
o Each thromboplastin is assigned an ISI number which is a sensitivity index
o This correction makes INR values comparable from lab to lab
o Normal INR = 1 (an INR of 2 means that their INR is 2 times higher than normal)

Same Patient-Same Blood
Reported by INR

Recommended Therapeutic Range for Oral Anticoagulant Therapy
(American College of Chest Physicians: Chest 1998; 114(suppl): 439-769s)

INR: 2.0-3.0
Prophylaxis or treatment of venous thrombosis
Treatment of pulmonary embolus
Prevention of systemic embolism
Tissue heart valves
Acute MI
Atrial fibrillation

Recommended Therapeutic Range for Oral Anticoagulant Therapy
(American College of Chest Physicians: Chest 1998; 114(suppl): 439-769s)
* INR: 2.5-3.5
o Mechanical prosthetic valves (high risk)
o Acute MI (to prevent recurrent MI)
o Certain patients with thrombosis and the antiphospholipid antibody syndrome (antibodies that interfere with the assembly of phospholipid complexes and thus inhibit coagulation)


Dental Management Guidelines
* There are no uniformly accepted guidelines for managing anticoagulated patients during dental treatment
* Previous AMA/ADA recommendation was that it was safe to perform surgery on a patient if the PT was 1.5-2.5x normal. This, however, is equivalent to an INR of 2.6-5.0 depending on the sensitivity of the various thromboplastins; an average PT of 1.6 = INR of 3!

* This clinical problem is not amenable to a “cookbook” approach
* Each patient must be considered individually and you must take into consideration the risk-benefit of stopping vs continuing anticoagulation (they are on anticoagulants because they are at risk for thromboembolism)
* Your decision depends upon:
o Medical condition/stability
o Degree of anticoagulation
o Magnitude of planned surgery
o Scientific evidence
* If questionable, decision should be a shared with physician

What does the scientific literature tell us?

* Updated a previous study (Wahl,MJ: Dental surgery in anticoagulated patients. Arch Int Med. 1998;158:1610-1616) and added more cases (26 studies)
* A review of more than 2400 cases of dentoalveolar surgery on more than 950 patients undergoing multiple extractions, full mouth exts, alveoloplasties whose anticoagulant was continued (many with INR > than therapeutic levels)
o 12 cases (0.5%) experienced bleeding that was uncontrollable by local measures alone
o Of these 12, 7 had an INR> than therapeutic levels & 3 were on antibiotics
o 3 required vitamin K administration to stop the bleeding

* Reviewed case reports of 493 patients whose anticoagulant had been discontinued prior to dental extractions and other dental procedures
* 5 pts (1%) suffered significant adverse outcomes
o 4 patients had fatal embolisms
o 1 patient had a non-fatal embolism

Devani,P: Dental extractions in patients on warfarin: Is alteration of anticoagulant regime necessary?
Brit JOMFS 1998;36;107-111

* Compared 2 groups of extraction patients undergoing an average of 2 extractions (range of 1-9 teeth)
o 32 pts with anticoagulant discontinued prior to surg with INR 1.5-2.1, and
o 33 pts with anticoagulant continued with INR of 2.3-3.4. Local measures only for hemostasis (atraumatic technique, sutures, gauze, etc)
* None in either group had significant post-op bleeding; 1 pt in each group required additional local measures to control delayed oozing
* Compared blood loss of 3 groups of dentoalveolar surgery pts
o 12 pts who continued anticoagulant with INR 1.2-2.9
o 13 pts who discontinued anticoagulant 3-4 days with INR 1.1-3.0
o 10 pts who were never on anticoagulant (INR not tested)
* No significant difference in blood loss among groups and no serious postoperative bleeding requiring intervention

* Conducted a systematic review and synthesis of the English language literature from 1966-2001 examining the perioperative management and outcomes of patients receiving long term oral anticoagulant therapy; included a comprehensive review of 26 case reports and studies examining bleeding and thromboembolism after dental procedures (minor ext, fmx, alveolectomies)
* Conclusion: Most patients undergoing dental procedures can undergo the procedure without alteration of the OAC regimen. The current literature suggests that the perioperative stroke rate for patients who have OAC withheld may be substantially greater than would be normally predicted

Conclusions
* It would thus appear that most patients who are on anticoagulant therapy (Coumadin) can undergo minor dentoalveolar surgery without discontinuance of anticoagulant using local/topical measures if:
o INR is within the therapeutic range (<3.5)
o No assoc aggravating conditions (e.g. antibiotics, liver or kidney disease)
o Planned surgery is “minor” (extractions, alveoloplasty, biopsy)
* If anticoagulant needs to be adjusted (INR>3.5), this is the responsibility of the physician

Antiplatelet Agents Normal Platelet Function

Platelets adhere to the area of injured endothelium (mediated by von Willebrand factor)
Platelets adhere to each other and form a scaffolding for fibrin deposition (von Willebrand
factor is a carrier protein for factor VIII)

Uses for Antiplatelet Drugs
* Prevention of heart disease
* During heart attack
* Unstable angina
* Following heart attack
* During or following angioplasty and stenting
* Prevention of stroke or TIA
* Atrial fibrillation (low risk patient)
* Peripheral vascular disease

Antiplatelet Drugs
* Aspirin (irreversible effect for life of the platelet ~ 7-10 days)
* NSAIDs (reversible effect; limited to duration of drug)
o Cox-1 (renal blood flow, fluid/electrolyte transport, stomach mucosal integrity, vasomotor tone, platelet aggregation)
o Cox-2 (inflammation)
* Clopidogrel (Plavix)
* Ticlopidine (Ticlid)
* Dipyridamole (Persantine)

Action of Antiplatelet Drugs
*The life of a platelet is about 7-10 days
Laboratory Tests to Monitor the Effects of Antiplatelet Drugs
* Ivy Bleeding time: measures the length of time a patient bleeds after a standardized incision.
o low reproducibility
o questionable sensitivity
o poor correlation to clinical bleeding tendency
o normal: 1-6 or 7 minutes
o conventionally, a bleeding time >20 minutes has been considered likely to result in clinically significant bleeding
* Platelet Function Analyzer (PFA-100)
o currently the most widely used autoanalyzer
o not yet available in all laboratories
o measures the time it takes to form a platelet plug across the aperature of a capillary tube
o normals: 60-120 seconds
o guidelines not currently available for application of PFA-100 results to clinical bleeding probability
Antiplatelet Drugs and Postoperative Bleeding?

* Very limited literature on this topic
* Most of the studies deal with aspirin
* Little information available on the other antiplatelet drugs
* Most of the recommendations are based upon clinical experience, case reports and expert opinion

Aspirin and Bleeding
* In all studies, aspirin was continued
* All three studies found no significant difference in perioperative or postoperative blood loss between patients taking aspirin and controls
* Medline review and analysis of all articles from 1966-2002 on surgery and bleeding complications due to aspirin
* No clinically relevant bleeding complications were reported for cardiovascular, vascular, or orthopedic surgery, or epidural anesthesia; there was an increase in clinically non-relevant bleeding induced by aspirin
* Conclusion: There is no scientific evidence to support the withdrawal of aspirin in patients prior to surgery
Current Practice in Great Britain
* The general consensus of opinion from this survey suggests that most vascular surgeons do not stop antiplatelet drugs preoperatively
Expert Opinion Canada
* Conclusion: Aspirin should not be withdrawn in most cases
o If pt is on aspirin, clopidogrel or ticlopidine and intraoperative bleeding is feared, a short-acting NSAID can be temporarily substituted

Summary: Antiplatelet Agents
* Clinical experience, expert opinion, anecdotal reports and available studies suggest that for most patients undergoing dentoalveolar surgery, it is not necessary to discontinue the use of aspirin or other antiplatelet agents if used alone. The use of these agents is not usually associated with significant (serious) operative or postoperative bleeding.
* If two agents are used together (e.g. aspirin and clopidogrel), the risk for bleeding is likely increased, and depending upon the extent of the surgery, should be discussed with the physician

Local Measures to Control Postoperative Bleeding
* Careful, atraumatic surgical technique
* Use of absobable hemostatic agent in socket (e.g. Gelfoam,Avitene,Surgicel)
* Careful suturing; primary closure over sockets not essential
* Post-operative pressure pack (damp gauze for 30-60 minutes); especially important for flap compression
* May use antifibrinolytic agents: tranexamic acid [Cyklokapron Oral] or epsilon amino caproic acid [Amicar] as a mouthwash or to soak pressure gauzes

Antifibrinolytic Mouthrinses
* Epsilon amino caproic acid (Amicar)
o Syrup (1.25 gm/5cc) , 5-10 mL QID X 7 days
o Use either as mouthwash or as a soak for the pressure gauze
* Tranexamic acid (Cyklokapron)
o Used topically as 10 mL of a 4.8% -5% weight/volume solution as a mouthwash for 2 minutes, QID, for 7 days
o Unfortunately, the 4.8% elixir is not FDA approved for use in the USA market

Additional Postoperative Measures

Management Considerations for Patients on Anticoagulants.ppt

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