1. Environmental Factors in WomensReproductive Health: Impact onChild Health and DevelopmentLeslie Rubin MDMorehouse School of MedicineDevelopmental Pediatric SpecialistsInnovative Solutions for Disadvantage and DisabilitySoutheast Pediatric Environmental Health Specialty Unit at Emory University

2. Human health problems on the rise Over the past 30 years, therehas been a significant rise inmany childhood disorders aswell as in hormonal andreproductive disturbances Early life exposure toenvironmental pollutants is aleading suspect. Some chemicals are directlytoxic to an exposed child whileother chemicals induce a chainof events that may culminatein a diagnosed health problemlater in life. 3. Children are More Vulnerable toEnvironmental Factors A developing child's chemical exposures are greater pound-for-pound than those of adults Children have lower levels of some chemical-bindingproteins, allowing more chemical to reach target organs Systems that detoxify and excrete industrial chemicals arenot fully developed An immature, porous blood-brain barrier allows greaterchemical exposures to the developing brain Organs and systems are rapidly developing, and thus areoften more vulnerable to damage from chemical exposureNational Academy of Sciences 1993 4. PediatricEnvironmental Health The childs environmentas a sum of Chemical Physical Biological & Social Factors The environment can impact thechilds growth, development, andwell-being for better or worse 5. BostonNew England PEHSUNew York CityMount Sinai PEHSUWashington DCMid-Atlantic Center for ChildrensHealth & the Environment PEHSUAtlantaSoutheast PEHSUCanadaKansas CityMid-America PEHSUTylerSouthwest Center PEHSUSeattleNorthwest PEHSUSan FranciscoUniversity of California PEHSUDenverRocky Mountain PEHSUChicagoGreat Lakes Centers PEHSUIrvineUniversity of California PEHSUGuadalajara, MexicoPEHSUMexicoAlaskaHawaiiVirginIslandsPuertoRicoEdmonton, CanadaPEHSU 6. Vulnerability of the Fetus However vulnerable a child is toenvironmental factors, the embryo andfetus are much more sensitive todisruptions even at low doses 7. Critical Periods in DevelopmentCentral nervous system (3 wks - 20 yrs)Ear (4-20 wks)Kidneys (4-40 wks)Heart (3-8 wks)Immune system (8-40 wks; competence & memory birth-10 yrs)Limbs(4-8wks)Skeleton (1-12 wks)Lungs (3-40 wks; alveoli birth-10 yrs)Reproductive system (7-40 wks; maturation in puberty)Source: Altshuler, K; Berg, M et al. Children's Health and the Environment, February 2003. 8. Thalidomide Thalidomide first entered the German market in1957 as a sedative, tranquilizer, and antiemetic. It was also proclaimed a "wonder drug" forinsomnia, coughs, colds, and headaches. It was advertised as completely safe foreveryone, including mother and child, evenduring pregnancy, as its developers could notfind a dose high enough to kill a rat. By 1960, thalidomide was marketed in 46countries, with sales nearly matching those ofaspirin! 9. Thalidomide In 1961, reports beganto emerge associatingthe drug with severebirth defects By March of 1962, thedrug was banned inmost countries where itwas previously sold An estimated 10-20,000infants were born withthis condition 10. Thalidomide - Lessons The field of Teratologywas given a start andresearch was directed tofinding what other drugscaused birth defects Regulations becamemore stringent on testingdrugs for safety duringpregnancy 11. Minamata Disease On April 21, 1956, a fiveyear-old girl was examinedat the Chisso Corporation'sfactory hospital inMinamata, Japan, The physicians were puzzledby her symptoms: difficultywalking, difficulty speakingand convulsions. They soon found otherfamily members and manyother children with thecondition 12. Minamata Disease On May 1, the hospital director reported an"epidemic of an unknown disease of thecentral nervous system - marking the officialdiscovery of Minamata disease By the end of the year Minamata disease wasconsidered to be a result poisoning by amethyl mercury that entered the bodythrough consumption of fish and shellfishfrom the Minamata Bay 13. Minamata Disease Chisso Corporation, achemical companylocated in KumamotoJapan, had dumped anestimated 27 tons ofmercury compoundsinto Minamata Bay. As of March 2001,2,265 victims had beenofficially recognized 14. Lessons Learned The placenta does notprovide full protection Mercury can cause braindamage in the unbornfetus Other heavy metals andtoxins can do the same Toxic chemicals need tobe regulated We need to monitor theconsumption of fishduring pregnancy 15. FDA Guidelines forChildren and Pregnant Women No more than 12-oz oflow mercury fish, (e.g.Cod & Canned Tuna) shouldbe consumed weekly. High" mercury fish, (e.g.Sea Bass & Bluefish) shouldbe kept to only three 6-ozservings per month. "Highest" mercury fish, (e.g.Marlin & Swordfish) shouldbe completely avoided 16. Congenital Rubella Between 1963 and 1965 a rubellaepidemic swept the nation. Children were mildly affected,but It caused 30,000 miscarriages and 20,000 pregnant women whocontracted the disease gave birthto infants with congenitalanomalies andneurodevelopmental disorders 17. Lessons Learned Infections in pregnantwomen (even supposedlymild ones) can have majorconsequences on theirunborn fetus Other similar conditionswere recognized - ToRCH Immunizations againstchildhood illnesses not onlyprevents complications inthe children but preventspotential effects on thefetus during pregnancy 18. Fetal Alcohol Syndrome In 1973 Jones and Smith published a report onthe first reported association between maternalalcoholism and aberrant morphogenesis in theoffspring the main features are pre and/or postnatal growth retardation, characteristic facial abnormalities, and central nervous system dysfunction, including mentalretardation Studies by the CDC report prevalence rates of FASalone from 0.2 to 1.5 cases per 1,000 birthsacross various populationsSmith, et al (1973) Lancet i, 12671271. 19. FAS Lessons Learned Alcohol and other drugstaken by the motherduring pregnancy canhave a deleteriouseffect on the growthand development of thefetus and child Warning labels onbottles of alcohol andeducation of public 20. Smoking During Pregnancy The embryos ofmothers who smokedtook 62 hours to reachthe eight-cell stage,compared to 58 hoursin non-smokers Increasing risk of lowbirth weight,prematurity and otherconsequences onembryogenesisFreour et al University of Nantes Presented at ESHRE meeting in Turkey 2012 21. Long-Term Consequences ofFetal and Neonatal Nicotine Exposure Studies suggest that nicotine may be a keychemical responsible for many long-term effectsassociated with maternal cigarette smoking onthe offspring, such as hypertension type 2 diabetes, obesity respiratory dysfunction neurobehavioral defects impaired fertilityBruin et al Toxicological Sciences 116: 364-374 2010 22. Tobacco Lessons Learned The effects of thetoxin not only have adirect effect on thesmoker and on thegrowth of the fetus but can have longterm healthimplications for therest of that childs life And for that childsoffspring as well 23. Diethylstilbestrol (DES):The Promise Diethylstilbestrol (DES) is a synthetic estrogenthat was developed to supplement a woman'snatural estrogen production. First prescribed in 1938 for women whoexperienced miscarriages or premature deliveries DES was originally considered effective and safefor both the pregnant woman and the fetus 24. Diethylstilbestrol (DES):Alarms! In 1971, the FDA issued a Drug Bulletin advisingphysicians to stop prescribing DES to pregnantwomen because it was linked to a rare vaginalcancer in female offspring. An estimated 5-10 million people in the USAwere exposed to DES during 1938-1971 25. Diethylstilbestrol (DES):What we Know Now Women prescribed DES while pregnant are at amodestly increased risk for breast cancer. Women exposed to DES in utero, are at anincreased risk for: clear cell adenocarcinoma (CCA) of the vagina andcervix, reproductive tract structural differences pregnancy complications, and infertility. Men exposed to DES in utero are at an increasedrisk for non-cancerous epididymal cysts. 26. Lessons Learned We cannot assume anydrug or chemical iscompletely safe even ifwe do not see immediateconsequences The effect may onlymanifest later in life or inthe next generation Therefore we need toadopt the precautionaryprinciple 27. Chemicals in our Environment EPA lists >80,000 chemicals in the USA 3,000-4,000 are high volume >1millionpounds per year 700 new chemicals introduced into the USAper year The Toxic Substances Control Act (TSCA)authorizes EPA to test