Transcript No Slide Title

Prevention of Birth Defects and
Disabilities
TH Tulchinsky MD MPH
Braun School Public Health
8 Jan 2006
NPH Ch 6
Public Health Importance
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Common – 3% of US children
Neonatal and infant mortality – 20% of IMR
Progress made primary, secondary and tertiary Px
Preventable – e.g. Folic acid
Education – KABP among women in age of fertility
Screening – PKY, CH etc
Intervention – FA fortification
Human genome project - new science and methods
Long term care – family and societal burden
Causes of Birth Defects
Physiologic
LBW
HDN
Nutritional
Iodine and iron
deficiency
Folic acid deficiency
Infectious
Rubella syndrome
STIs – Syphilis, GC,
HIV
CMV
Unknown
Cerebral palsy
Toxic
FAS
Smoking, alcohol, drugs
Genetic
PKU
CH
Thalassemia, Sickle Cell
Tay Sachs etc
Injury
Program Approach
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High risk population groups
Multiple causation
Toxic – alcohol, drugs, medications
Nutrition – anemia, HDN
Physiologic - HDN
Infection – syphilis, GC, HIV etc
Genetic screening and counseling
Trauma – accidents and violence
Multiple interventions
Non Genetic Maternal-Fetal Transmission
• Physiologic
– Rhesus hemolytic anemia (Rh syndrome)
– Hemorrhagic disease of newborn (HDN)
• Toxic
– Thalidomide
– Fetal alcohol syndrome
– Crack babies
– Smoking
Maternal-Fetal Infectious Transmission
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GC conjunctivitis
Syphilis
TB
Syphilis
Cytomegalovirus
HIV/AIDS
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Congenital rubella
Mumps
Toxoplasmosis
Vaginitis
Preventing Infectious Disease
Transmission, Mother-Infant
• Prevention of Congenital Rubella Syndrome
– Immunize school girls
– Immunize total population (MMR)
• Prevention of Syphilis, GC, CMV and HIV
– Educate
– Case find
– Treat
– Contacts ?
GC Opthalmia Neonatorum
• Common cause of blindness 19th C
• Crede in Vienna experimented with many
prophylactic preparations
• Silver nitrate
• Eradicated GC neonatorum blindness
• Mandatory eye care for newborns prevents millions
of cases of blindness
NPH Ch 6
Cytomegalovirus (CMV)
• Occurrence 0.2-2.2% of births worldwide
• 10% with congenital CMV symptomatic at birth and
90% have permanent neurologic handicap
• Other 90% will have 10% late CNS deficit mainly
sensory neuronal hearing loss
• Routine screening for asymptomatic CMV at birth
(urine viral culture) in first 3 weeks of life
• PCR Polymerase chain reaction easier and cheaper
• Cost benefit ratio currently in question
• Importance for future developments
Birth Defects due to Genetic Disorders
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PKU - phenylketonuria
CH – congenital hypothyroidism
Tay-Sachs disease
Sickle Cell anemia
Thalassemia
Cystic Fibrosis
Down’s syndrome
Cataracts
Congenital dislocated hips
Eradication of Beta Thalassemia Major in
Cyprus and Sardinia
Virtual eradication achieved in endemic areas; Cyprus, 14% of
the population carriers of Beta Thalassemia, and 1% of (1
in 158 births) had the disease. Now, rare in Cyprus,
Sardinia, Greece, UK.
Long-term program: education, screening, counseling.
Marriage between carriers reduced by community education
program. When marriage occurs, screening and termination
of affected pregnancies reduces Thalassemia Major births.
A model of elimination of a genetic disorder via a combination
of health education, screening and community support e.g.
Tay Sachs among Ashkenazi Jews.
Community Wide Programs for Prevention of
Birth Defects and Genetic Disorders
Iodization of salt prevents IDD brain damage; effective
enforcement and monitoring
Folic acid fortified flour reduces neural tube defects
Rubella immunization before pregnancy prevents
congenital rubella syndrome (CRS)
Px and Rx of STDs prevents congenital syphilis,
gonorrhoea, CMV and HIV infections
Hep B immunization prevents maternal-fetal
transmission
HIV antiretroviral Rx protects newborn, breast fed
baby
Prenatal Prevention
Cessation of smoking, alcohol and drug intake
Pre-pregnancy and pregnancy nutrition counseling to
promote optimal fetal development
Genetic counseling for parents at risk, e.g.
consanguineous marriages
Avoid unnecessary medication
Iron, folic acid and multivitamin supplements (and
iodine if salt not fortified)
Risk assessment and referral to high risk care
program e.g. ultra sound and amniocentesis
Toxic Causes
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Heavy metals
Thalidomide
Anti-epileptics
Crack babies
Fetal alcohol syndrome (FAS)
Smoking
Genetic Disorders
• Transmission from one parent (dominant)
– Huntington’s chorea
• Transmission from both parents (recessive)
– Thalassemia
– Sickle cell
Cerebral Palsy (CP)
Group of neurological disorders occurring in about
1/400 births, causing motor disabilities
Associated with mental retardation, seizure disorders,
motor spasticity or sensory problems.
Rel to low birth weight (<2,500 grams), especially
very LBW (<1,500 grams)
Intracranial hemorrhage, Rh incompatibility, intrauterine and birth trauma, maternal exposure to
heavy metals such as mercury, and other
unidentified factors (?HDN)
Some 20% due to intrauterine fetal hypoxia
Cystic Fibrosis (CF)
• Commonest lethal genetic disease in the US white
population, in 1/2,000 live births (1/3000 in
Canadian study)
• Recessive gene present in 5% of the white
population and 2% of blacks in the US
• Causes production of abnormally thick mucus in
the lungs, intestines and other glands,
• Chronic obstructive lung disease, repeated
infections, and destruction of lung tissue.
• Frequent hospitalization and death, even with best
of care, by age 30 (median age of death is 24)
Cystic Fibrosis Prevention
• Prenatal screening with chorionic villus sampling
or amniocentesis.
• Screening pregnancies with a previous CF birth can
prevent a second CF child, but general population
screening is not yet available.
• Early diagnosis, support and education of parents
can improve the duration and quality of life of CF
person.
• Treatment complex, costly, multidisciplinary
approach. Gene therapy techniques is becoming
available to improve case management
Physiologic
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Rh
Hemorrhagic Disease of Newborn
Smoking
LBW
Nutritional
Smoking
Nicotine reduces placental blood flow
Complications- premature delivery
Pregnant smokers eat more but babies weigh less
LBW causes 300,000 deaths in US annually
Nicotine found in breast milk
Smoking associated with SIDS
Smokers 3-4x risk
Secondary exposure 2x risk
Hemmorhagic Disease of Newborn (HDN)
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Physiologic deficiency of prothrombin
Common – early and late (at 1-2, and 2-12 weeks)
High risk in LBW and breast fed babies
Vitamin K since 1950s
Controversies in Europe in 1990s
Reconfirmed as routine prophylaxis e.g. NY State
Vital in routine infant care - mandatory
American Academy of Pediatrics,
Committee of Nutrition.
Pediatrics. 1961
American Academy of Pediatrics,
Committee of Nutrition.
Pediatrics. 2003
Israel Experience HDN
• Vitamin K widely used and increasing , but far from
universal practice in the 1970s
• In 1977, HDN deaths in Israel were 131/100,000 live
births; declined to 31/100,000 live births in 1984
and 3/100,000 in 1988
• In 1984, vitamin K made mandatory for newborn
care by the Ministry of Health
• Subsequent large decline in deaths from intracranial and intra-ventricular hemorrhage, may be
partly due to routine use of vitamin K
Israel Ministry of Health
New York State HDN Review
• We reviewed vital statistics in New York State
finding infant deaths and hospitalizations attributed
to neonatal hemorrhagic conditions
• Case record reviews showed absence of recorded
giving vitamin K in 65% of deaths; others given
after bleeding began
• Vitamin K not included in standing orders in any of
22 hospitals contacted
• Review led to vitamin K being made a mandatory
newborn care procedure in NY State Public Health
Code
Tulchinsky TH, et al.
Am J Public Health, 1993;83:1166-1168
Primary HDN
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Often fatal condition
Diffuse hemorrhage in otherwise healthy infant
During the first week of life
Particularly in low birth weight babies
Results of low levels of prothrombin and other
vitamin K dependent clotting factors, (Factors II,
VII, IX and X) caused by vitamin K deficiency
• An exaggerated of physiologic deficiency of clotting
factors normal in the first few days of life
• Incidence between 2.5 to 17.0 per thousand
newborns not given vitamin K prophylactically
Late HDN
• Between 2-12 weeks of life,
• Primarily in breast-fed babies without, or
inadequate, or late vitamin K
• Immaturity of liver affects production of
clotting factors
• Late HDN rates of 4.4-7.2/100,000 live births
• Increasing reports in developing countries e.g.
India
Intracranial Hemorrhage in Late HDN
• Infants (n = 42) present with late HDN, 1998-2001
• Most (76%) in the age group of 1-3 months.
• All term babies on exclusive breast-feeding and none
received vitamin K at birth
• 71% patients presented with intracranial hemorrhage,
commonest site - intracerebral and multiple ICH.
External bleeding in 1/3 of patients only; 3 died
• Late HDN important in developing countries where
vitamin K prophylaxis is not routinely practiced.
• Isolated intracranial hemorrhage is a common mode of
presentation.
Pooni PA, Singh D, Singh H, Jain BK
Indian Pediatr. 2003 Mar;40(3):243-8.
Micro Nutrient Deficiency (MND)
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Iron deficiency and anemia
Iodine deficiency – cretinism
Low birth weight
Vitamin B deficiency - beriberi
Folic acid deficiency
– NTDs reduced by 70%
– Down’s
– Congenital heart conditions
Neural Tube Defects (NTDs)
Defects of neural tube - brain, spinal cord.
Range of abnormalities, from anencephaly, a
markedly defective development of the brain to
spina bifida, defective closure of spinal column.
NTDs vary in degree of severity but many require
extensive surgical and medical care.
NTDs occur in 2/1,000 births in North America, but
incidence is declining due to screening in
pregnancy and primary prevention through folic
acid pre-pregnancy and in early pregnancy.
Preventing NTDs
• Screening for NTDs since early 1970s with
amniocentesis, later in blood tests for alpha fetoproteins (AFP) and ultra sound
• In 1980s, UK MSC showed that folic acid before
pregnancy greatly reduces the chance of NTDs.
• Pre-pregnancy compliance with recommended folic
acid supplement in US was + 30%
• Fortification of flour with FA adopted by US FDA,
Canada, Chile for primary prevention of NTDs with
supplements for planned pregnancies to assure 100%
RDA intake
• FA supplementation but not fortification in Europe
Preventive Measures for CP
• Reduce low birth weight by improving maternal
nutrition, smoking cessation during pregnancy
• Improve prenatal care and labor/delivery
• Vitamin K at birth
• Reduce birth trauma
• Professionally trained midwives reduces risk of CP
• Prevention is limited by lack of identification of
many causative factors
Mental Retardation
Mild retardation (IQ of 50-70): perinatal and post-natal
factors, including LBW or asphyxia at birth
Severe retardation (IQ < 50) in 3-5 per 1,000 newborns
Prevention requires well-organized prenatal, perinatal and
postnatal care.
Prenatal factors associated with CP and seizures
More than 1/3 are due to chromosomal abnormalities e.g.
Phenylketonuria, Down’s
Others - congenital rubella, congenital hypothyroidism
Mental Retardation
Pregnancies > 35 (role of folic and iron deficiency?)
Congenital rubella and hypothyroidism
Downs syndrome
Maternal infections toxoplasmosis, cytomegaloviruses
Late pregnancy > age 35
Pregnancy complications: toxemia, urinary tract
infections and anemia increase risk of retardation
Prenatal diagnosis, amniocentesis in pregnant women
over age 35 and termination of affected pregnancies.
Newborn Screening for Congenital
Disorders and Followup Management
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Tay Sachs
Sickle cell disease
Thalassemia
Phenylketonuria (PKU)
Congenital hypothyroidism (CH)
Other metabolic disorders
Mandatory Screening, US Establishing
Principles
1. Universal newborn screening is an essential public health
responsibility critical to improve health outcomes
• Development should adressed by what is in the best
interest of the affected newborn, also unaffected newborns,
families, health professionals, and the public
• 3. NS is more than testing. It is a coordinated and
comprehensive system consisting of education, screening,
follow-up, diagnosis, treatment and management, and
program evaluation.
• 4. The medical home and the public and private
components of the screening programs should be in close
communication to ensure confirmation of test results and
the appropriate follow-up and care of identified newborns.
Selection of Screening Conditions
• Meet the following minimum criteria:
• It can be identified at a phase (24-48 hours
after birth) and not ordinarily be clinically
detected;
• A test available with appropriate sensitivity
and specificity
• Demonstrated benefits of early detection,
timely intervention and efficacious treatment
of the condition
• Centralized health information data collection
longitudinal assessment of disease
Choosing Conditions
• Conditions chosen for evaluation included for one or
more of several reasons:
• Included in private, state, or national newborn
screening programs;
• Coincidentally revealed by some technologies used in
newborn screening;
• Identified by members of the expert group as worthy
of consideration
• Identified by disease-specific advocacy organizations;
• Included in the differential diagnosis of a screening
result for another condition.
Program Approach to Birth Defects
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Education
Pre-pregnancy counseling
Screening and management
Nutrition, food fortification
Genetic counseling
Gov’t, UNICEF, voluntary organizations (March of
Dimes)
Pre Pregnancy and Prenatal Prevention
• Stop smoking, alcohol and drug intake to prevent
fetal damage
• STD, HIV testing
• Nutrition counseling
• Folic acid and iron
• Genetic counseling re consanguineous marriages
• Tay Sachs screening
• Thalassemia and Sickle Cell screening
Pre Pregnancy and Prenatal Prevention
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Avoid unnecessary medication
Physical fitness
Dental health
General counseling
Iron, folic acid, iodine, multivitamins
Pregnancy risk assessment
Referral for high risk care
Prenatal care protocol starting in T1
Priorities
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Educate women, care givers
Birth Defect Registry
Review all infant and maternal deaths
Mandatory Vitamin K and eye care for all newborns
Folic acid, iron and vitamins B in flour
Iron, folic and vits B supplements during pregnancy
Smoking, alcohol cessation before, during pregnancy
Rubella eradication MMR x2 (boys and girls)
Rh management
Priorities II
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Prenatal care and risk screening
Treat STIs
Screen newborns for PKU, CH, etc.
Educate and screen for thalassemia, sickle cell
anemia
• Hepatitis B part of routine immunization
• LBW prevention – nutrition, supplements, IDA,
infections
• Treat maternal HIV
Birth Defects/Disorders for Primary, Secondary
and Tertiary Prevention, a Program Approach
• Multiple causation e.g. low birth weight, mental retardation
and developmental disability (MRDD)
• Toxic e.g. thalidomide, fetal alcohol syndrome, crack babies
• Nutritional e.g. folic acid and NTDs, iodine and iron
deficiency
• Physiologic e.g. vitamin K deficiency hemorrhagic disease,
Rh hemolytic anemia
• Infection e.g. rubella syndrome, congenital syphilis,
cytomegalovirus, HIV, gonococccal conjunctivitis
• Genetic e.g. phenylketonuria, thalassemia, sickle cell disease,
congenital hypothyroidism, cystic fibrosis, Down syndrome,
autism, fragile X syndrome, and many others
Summary and Conclusion
• Prevention of birth defects, disabilities, congenital
disorders involves wide range of public health and
individual care measures
• Human Genome Project will increase potential
• MNDs prevention cost effective
• Genetic, toxic, infectious and nutritional factors all
important for health of newborns
• Strategic planning
• Education – public and professional
• Governmental, NGO and individual responsibility
Objective Healthy Children
References
• Tulchinsky TH, Varavikova EA. The New Public Health.
Academic Press, San Diego, 2000, chapter 6
• American Academy of Pediatrics. Serving the family from
birth to the medical home. A report form the Newborn
Screening Task Force, Washington DC, May 1999.
Pediatrics. 2000;106:S391-3.
• Bailey DB, Skinner D, Waren SF. Newborn screening for
developmental disabilities: reframing presumptive benefits.
Am J Public Health. 2005;95:1889-93.
• http://mchb.hrsa.gov/screening/summary.htm
•CDC. Economic costs of birth defects and cerebral palsy---United States, 1992.
MMWR 1995;44:694--9.
•CDC. Spina bifida and anencephaly before and after folic acid mandate--United States, 1995--1996 and 1999--2000. MMWR 2004;53:362--5.
•Centers for Disease Control. Improved National Prevalence Estimates for 18
Selected Major Birth Defects, United States, 1999—2001. MMWR Weekly
2006; 54:pps.
•Waitzman NJ, Romano PS, Scheffler RM. Estimates of the economic costs of
birth defects. Inquiry 1994;31:188-205.
•Centers for Disease Control. Improved National Prevalence Estimates for 18
Selected Major Birth Defects --- United States, 1999—2001. MMWR.
2006;54(51&52);1301-05.