Morris Cohen, MDConflict of interest statement

• As required:• I do not have a financial interest or

affiliation with any interests concerning any material I will discuss in my presentation.

• I am not going to discuss any non-FDA approved or investigational drugs or medical devices.

Lead & Beyond

Friday April 16th, 2010

Morris Cohen, M.D.Director Neonatal Medicine Children’s Hospital of NJ

Co-Director Regional Perinatal Center at NBIMCMember of Governor’s Council For the Prevention of

Developmental Disabilities

• Persistent toxins found in the air, water, soil and food are also in the bodies of American adults and children

(CDC, 2005; EPA, 2003)

• All US citizens are vulnerable and repeatedly exposed to toxic chemicals including:

• Lead• Mercury• Manganese• Methylmercury• Cotinine

• Solvents• Plasticizers• Bisphenol A• Brominated Flame

Retardants• Pesticides• Chemicals• Dioxin Sattler, B, 2008

Persistent Bioaccumulative Toxicants (PBT’s)

• Most are chemicals that did not exist on earth before the last century

• Man-made chemicals that comprise stores of industrial chemicals, pharmaceuticals, household products, and personal care products

• Aside from pharmaceuticals, little to no toxicity testing required by manufacturers before brought to market

Persistent Bioaccumulative Toxicants (PBT’s)

• Studies show that PBT’s may present a wide range of risks including:– Neurotoxic– Immunotoxic– Carcinogenic– Teratogenic– Endocrine Disruptors– Learning Disabilities– Behavioral Problems– Low Birth weight– Asthma

Environmental Pollutants that place Newborns at Risk

• Lead• Methylmercury• Pesticides • Cotinine• Organic solvents

Lead Exposure: Who’s at Risk?

Nearly one-half million, children primarily those who are poor,

belong to a minority population, or live in older houses and in

poor urban areas, continue to be at risk

Effects of Lead on Body Systems

Central Nervous SystemLead easily crosses blood-brain barrier

Hematologic SystemBinds to RBCs; inhibits enzymes, causing

anemiaRenal System

Damage to the proximal tubules of the kidneyo Aminoaciduria, glycosuria, hyperphosphaturia

Skeletal SystemLead can remain up to 30 years in bone

Effects of Lead on Body Systems

Reproductive System risk of hypertension in pregnant women (Rabinowitz)

risk of miscarriage bone metabolism during pregnancy & lactation

o results in stored lead leaving the bone and re-entering the circulation - blood lead levels may increase by up to 20% even in women with low levels. (Gulson)

Lead readily crosses the placentao The fetus may be at risk from mother’s exposure in childhood fetal blood levels

- Premature birth- Fetal malformation & death- Neurobehavioral deficits

Symptoms of Lead ToxicitySymptoms may be subtle and can go unnoticed until

blood levels reach 40 mcg/dl or higher

• At low levels – Irritability and other non-specific symptoms– neurobehavioral impairment

academic ability IQ scores in children ages 5 & younger• Impaired neurobehavioral development in children at age 7½ years• Deficits in academic & cognitive skills in children & adolescents

• As levels approach 40– Headache, abdominal pain, anemia, vomiting

• Blood levels of 70 to 80 – Encephalopathy: ataxia, convulsions, coma– High incidence of permanent neurologic damage

Health Effects of Lead in Children & Adults CHILDREN Blood

μg/dl ADULTS Blood μg/dl

↓ ALA-Dehydrase <5 ↓ ALA-Dehydrase <5

Neurodevelopmental <10 ↓ GFR <10

Sexual Maturation <10 Blood Pressure <10

Depressed Vitamin D >15 EP (females) >20

Erythrocyte Protoporphyrin >15 Proteinuria >30

↓Nerve Conduction Velocity >30 Peripheral Neuropathy >40

↓Hemoglobin >40 Neurobehavior AbN >40

Colic >60 Thyroid Hormone >40

Reduced Fertility >40

↓ Hemoglobin >50

Occupational Exposure to Lead94% of adults with identified lead-exposure were 94% of adults with identified lead-exposure were exposed via occupational sourcesexposed via occupational sources CDS, 2004

Ammunition/Explosives MakerAuto Repair/Auto body WorkBattery Manufacturing and RepairBridge, Tunnel and Elevated Highway ConstructionBuilding or Repairing ShipsCable/Wire Stripping, Splicing or ProductionCeramics Worker (Pottery, Tiles)ConstructionFiring Range WorkGlass Recycling, Stained Glass and GlassJewelry Maker or RepairLead AbatementLead AbatementLead MinerLeaded Glass Factory WorkerManufacturing and Installation of Plumbing Components

Manufacturing of Industrial Machinery and EquipmentMelting Metal (Smelting)Metal Scrap Yards and Other Recycling OperationsMotor Vehicle Parts and AccessoriesOccupations Using FirearmsPaint/Pigment ManufacturingPottery MakingProduction and Use of Chemical PreparationsRadiator RepairRemodeling/Repainting/Renovating Houses or BuildingsRemoving Paint (Sandblasting, Scraping, Sanding, Heat Gun or Torch)Steel MetalworkTearing Down Buildings/Metal StructuresWelding, Burning, Cutting or Torching

Traditional/Folk Remedies or Cosmetics That Have Been Found to Contain Lead:

ASIAN, AFRICAN, AND MIDDLE EASTERN COMMUNITIES:• (as a cosmetic or a treatment for skin infections or umbilical stump)

– alkohl, kajal, kohl, or surma (black powder)

HMONG COMMUNITIES:• (for fever or rash)

– pay-loo-ah (orange/red powder)

LATINO COMMUNITIES:• (for abdominal pain/empacho)

– azarcon (yellow/orange powder)– also known as:alarcon, cora, coral, liga, maria luisa, and rueda greta

(yellow/orange powder)

SOUTH ASIAN (EAST INDIAN) COMMUNITIES:• (bindi dot)• sindoor (red powder)• (dietary supplement)• Ayurvedic herbal medicine products (HMPs)

Environmental Exposure to LeadHobbies & other pursuits

– Bronze Casting– Collecting, Painting, or Playing Games with Lead Figurines– Copper Enameling– Electronics with Lead Solder– Hunting and Target Shooting– Jewelry Making with Lead Solder– Liquor Distillation– Making pottery and Ceramic Ware with Lead Glazes and

Paints– Making Stained Glass and Painting on Stained Glass– Melting Lead for Fishing Sinkers or Bullets or Lead

Figurines– Painting/Stripping Cars, Boats, and Bicycles– Print Making and Other Fine Arts (When Lead White, Flake

White and Chrome Yellow Pigments are Involved)– Remodeling, Repairing, and Renovating Homes

ENVIRONMENTAL LEAD EXPOSURE

• Paint– 70% of homes built prior to 1960 contain lead paint & ~ 25% of US

homes with one or more children under the age of six contain exposed lead

– Deterioration or renovation can release lead into air (inhaled +/or settle in soil, creating hand-to-mouth exposure

• scraping, sanding, or burning of lead-based paint on woodwork, walls• sanding, stripping or burning or lead-based painted furniture

• Pica– 3% of adults with blood levels 25mcg/dl (ABLES, 2003-2004)

• Painted toys• Water

– Drinking water accounts for ~ 10-20% of lead exposure in children– Homes built before 1986 may have lead pipes, fittings and solder

• Contaminated foods and candy

ESSEX COUNTY Lead Levels > 10 ug/dl in Children & Pre-1950 Housing Units

HUNTERDON COUNTY Lead Levels > 10 ug/dl in Children & Pre-1950 Housing Units

Preventive Public Health Strategies

• CDC and AAP recommends– Screening of all Medicaid-eligible children– Targeted screening of children who are not

eligible for Medicaid

Screening: Children• Children should be screened according to state

recommendations• In the absence of recommendations, the CDC

suggests that: – Blood lead levels be determined at one & two years of age– Children 36-72 months should be tested

• if they haven’t previously been screened • if they live in a zip code in which >27% of housing was built

before 1950• If they receive public assistance• If a parent or guardian answers “yes” or “don’t know” to any of

the following 3 questions:– Does your child live in or regularly visit a house that was

built before 1950?– Does your child live in or regularly visit a house built

before 1978 with recent or ongoing renovations or remodeling (within last 6 months)?

– Does your child have a sibling or playmate who has or did have lead poisoning?

Lead Exposure in Pregnancy

• Research has shown that blood lead levels in pregnant women well below the CDC’s “level of concern” of 10mcg/dl can cause:– Miscarriage– Premature birth– LBW– Subsequent developmental delays in their children– Hypertension in pregnant women

• During pregnancy & lactation increased bone metabolism results in stored lead leaving the bone and re-entering the circulation

• Blood lead levels may increase by 20% or greater during pregnancy, even in women with low levels

Major Health Effects of Lead Exposure in Children

If not detected early, children with high levels of lead can suffer from:– Damage to the brain and nervous system– Behavior and learning problems– Slowed growth– Hearing problems– Headaches

Lead and the Developing Fetus• Strong correlation between maternal and umbilical cord blood

lead levels– At time of delivery, infant’s blood lead levels were, on average,

19% higher that those of their mothers (Shannon and Colleagues)

• Maternal Bone Lead Levels is inversely correlated with MDI at 24 months (Gomaa et et Pediatrics 2002;110-118)

• The effect of lead on the fetus’s CNS is greater during gestation and in the first 36 months of life than it is later in life because of very rapid growth and the incomplete blood-brain barrier– Destructive to the developing CNS– Interferes with synaptic mechanisms for neurotransmitter release– In animal studies, lead-related losses in developmental areas such

as visual-motor integration and increased errors in tasks of perseverance have pointed to the hippocampus as the area of injury Goyer, 1996

Screening: Pregnant Women

• No national organizations currently recommend screening pregnant women for elevated lead levels

US Preventive Services Task Force, 2006

• New York & Minnesota– Recommend that pregnant women receive

initial screening questionnaire• If “yes” or “don’t know” to any of the 7

screening questions, a blood test for lead should be performed

Minnesota Questionnaire to determine if a pregnant woman is at risk for current high-dose exposure to lead.

(Adapted from a risk assessment questionnaire for children developed by the CDC)

• Do you or others in your household have an occupation that involves lead exposure? (See Section A.)

• Sometimes pregnant women have the urge to eat things that are not food, such as clay, soil, plaster or paint chips. Do you ever eat paint chips?

• Do you live in an old house with ongoing renovations that generate a lot of dust (e.g., sanding and scraping)?

• To your knowledge, has your home been tested for lead in the water, and if so, were you told that the level was high? (Note: a level over 15 parts per billion (ppb) or micrograms per liter (ug/L) is considered high.)

• Do you use any traditional folk remedies or cosmetics that are not sold in a regular drug store or are homemade, which may contain lead? (Sec. B.)

• Do you or others in your household have any hobbies or activities likely to cause lead exposure? (See Section C.)

• Do you use non-commercially prepared pottery or leaded crystal?

•Testing is not recommended for women who are not at risk. •If the woman answers “yes” to any of the questions or if she has moved to Minnesota from a major metropolitan area or another country within the last 12 months, she is at risk for current high-dose lead exposure and should have a blood lead test.

Methods to Reduce Lead Exposure in Pregnant Women

• Discuss with your employer ways to reduce possible lead exposure

• Damp mop and damp dust rather than sweep and dry dust• Avoid drinking acidic liquids from imported ceramic cups and

mugs, or from leaded crystal• Avoid traditional folk remedies which might contain lead• Avoid cosmetics which might contain lead• Avoid lead related crafts to avoid exposure to lead• Wash hands thoroughly before meal preparations• Run water from the faucet for at least a minute until it runs cold

before collecting for drinking and cooking• Don’t be in the home when renovations that may involve lead-

based paint are taking place• Don’t clean up after renovations involving lead-based paint• Don’t strip paint from antique furniture such as cribs and

rocking chairs• Don’t store food in open imported cans

Nutritional Information for Pregnant and Lactating Women

• Eat frequent and regular meals - environmental lead is more easily absorbed on an empty stomach

• Iron or calcium deficits promote lead absorption – A diet rich in iron and calcium reduces the absorption of lead– Calcium supplements made from bone should be avoided as

they may contain lead

• Breastfeeding is generally safe even if a woman has an elevated blood lead level. – if a mother with an elevated blood lead level is

breastfeeding, the infant’s blood lead level should be carefully and frequently monitored

Feeding & Caring for the Baby

• Breast milk is usually best for babies, even if the blood lead level is elevated.

• If baby formula is used, take care when preparing it. – Use cold tap water – not hot- to make infant formula. – Let the cold water run for at least a minute, to flush any lead

picked up from the pipes. – Purchase bottled water if the home’s drinking water exceeds the

Environmental Protection Agency’s action level of 15 ppb.• Feed the baby foods that get ahead of lead.

– Iron fortified formula and cereals can lower you’re the family’s lead risk.

• Attached the pacifier to the baby’s shirt to prevent it falling on the floor

• Wash the pacifier often– This will help remove any lead dust

• Take the baby for regular health care visits and follow the health provider’s lead test advice

Mercury

• Metal present in the environment– Elemental (pure) form

• Thermometers, dental fillings (amalgam), some batteries

– Methylmercury• Fish is the main source

– Highest levels in large fish that eat smaller fish

• FDA and EPA advise pregnant women to avoid eating swordfish, shark tilefish, and limit consumption of albacore tuna to < 6 oz per week

Major Health Effects of Methylmercury Poisoning

• Fetuses, infants, children– Impaired neurological development

• Impacts cognitive thinking, memory, attention, language, and fine motor and visual spatial skills

• All ages– Impairment of peripheral vision– Disturbances in sensations (“pins & needles”)– Lack of coordination of movements– Impairment of hearing, speech, walking– Muscle weakness

Cotinine

• Nicotine metabolite

• Accumulates in the blood and urine following tobacco smoke inhalation

• Children with greater exposure to environmental tobacco smoke were significantly more likely to have more severe asthma, an increased number of respiratory illnesses, and lower lung function

Organic Solvents

• Chemicals that dissolve other substances– Paint thinners, varnish removers, lacquers, inks and paints

• Associated with toxicity to the nervous system, reproductive damage, liver and kidney damage, respiratory impairment and cancer

• A 1999 Canadian study found that women exposed to solvents on the job during their first trimester were 13 times more likely than unexposed women to have a baby with a major birth defect, like spina bifida, clubfoot, heart defects, deafness

(Khattak, et al, 1999)

Organic Solvents

Pregnant women who work with solvents, including women who do arts and crafts at home, should minimize their exposure– Making sure workplace is well ventilated– Wear appropriate protective clothing

• Gloves, mask

– Never eat or drink in work area

Pesticides• There is little proof that exposure to pest-

control products at levels commonly used at home pose a risk to the fetus – However all insecticides are to some extent poisonous

• Some studies suggest that high levels of exposure to pesticide may contribute to miscarriage, preterm delivery and birth defects

(AAP Committee on Environmental Health, 2003)

Cohort Studies to Assess the Prenatal Consequences to Environmental Pollutants

NCS National Children’s Study (USA) 100,000Avon Longitudinal Study of Parents and Children (UK) 15,000Danish National Birth Cohort 100,000INMA INfanfancia y Medio Ambieente Environment and Childhood (Spain)

3,100

Tohoku Study of Childhood Development (Japan)

1,000

Hokkaido Cohort Study. (Japan) 20,000CHEER The Child Health Environmental Research Study. (Korea)

MOCEH (Korea) Mothers & Children’s Environmental Health Study. (Korea)

1,500

Children have Special Vulnerabilities• Children have special vulnerabilities to these

environmental risks– biological– behavioral – socio-economic

• There is a growing concern about the potential health effects of these contaminants on the immature systems of developing fetuses and young children and the potential for long-term consequences even into adulthood.

• Environmental standards are not always protective of children’s health