Toll FREE (866) 626-6847 www.MotherToBabyCA.org

∗ Formerly known as CTIS (California Teratogen Information Service) Pregnancy Health Information Line

∗ Established over 30 years ago for the State of California. Funded (partially) by Department of Education, grants and donations. Based in Pediatrics, School Of Medicine at UC San Diego

∗ FREE and confidential telephone and e-Mail service providing pregnancy and breastfeeding health information - no insurance or appointment needed! Try new online chat service

∗ MOM & BABY FOLLOW-UP: FREE specialized pediatric exam and neuro-developmental exam (Research)

∗ California affiliate of MotherToBaby/Organization of Teratology Information Specialist (OTIS)

Who is MotherToBaby California

Teratogen Is Any Substance: ∗ a mother is exposed to during pregnancy ∗ That can interfere with the normal development of her

baby; causes a pattern of minor and major malformations

Behavioral Teratogen is any substance: ∗ That causes impaired cognitive, affective, social,

reproductive, and/or sensorimotor behavior effects even in the absence of obvious physical/structural problems

What is a Teratogen ?

MotherToBaby CA provides evidence-based information

∗ Prescription and Non-Prescription Medications ∗ Vaccines, Infections, Diseases and Fever ∗ Alcohol, Tobacco, Illicit Drugs ∗ Chemical or Occupational Exposures

Some commonly asked questions:

When is it safe to have a drink a glass of wine, only after 1st trimester?

We’re planning to get pregnant and I’m breastfeeding. But I WANT to get an Seasonal Flu vaccine?

Do I have to quit taking my antidepressant, or switch to a safer drug?

I’ve just diagnosed with Gestational Diabetes, will my medications cause birth defects

How much does mom share with her baby?

How much alcohol is safe during pregnancy?

GROWTH: prenatal / postnatal growth deficiency PERFORMANCE: (developmental delay):

∗ poor attention span & school performance (avg IQ 63) ∗ irritability, hyperactivity, fine motor dysfunction

FACIES: Microcephaly, short palpebral fissures (eye slits), elongated, smooth philtrum,

thin vermillion (lip) maxillary hypoplasia

FETAL ALCOHOL SYNDROME (FAS)

FAS(D) under-recognized

∗ Difficulty in making the diagnosis, especially in the newborn period or in adolescents and adults

∗ Lack of expertise among general pediatricians, or poor access to expert diagnostic teams

∗ Lack of a clearly defined/distinct neurobehavioral phenotype ∗ Under-ascertainment of alcohol use by pregnant women

Stoler JM et al J Pediatr 135:430-6 (1999) Elliott EJ et al J Paediatr Child Health 42:698-703 (2006) Elgen I et al Acta Pediatrica 96:237-41 (2007)

∗ Looking at the broader spectrum of FAS, ARND, ARBD

Population-based study in Seattle, WA measured rate of FAS at 3.1 per 1000 but full spectrum of FASD measured to be at leasat 9.1 per 1,000 or 3-9 times greater than rates of FAS alone

Sampson et al Teratology; 56:317-26 (1997

Everyone will have QUESTIONS, but why search the internet?

MotherToBabyCA.org has ANSWERS!

Causes of Birth Defects

Birth Defects is a leading cause of infant death in California and the United States

Teratogens 10% Chromosomal Defects 10% (i.e. Downs Syndrome) Single Gene Defects 20% (i.e. Tay-Sachs, Cystic Fibrosis) Unknown Causes 60% Multiple malformations Isolated Congenital Defects There is a 4% baseline risk of birth defects in any pregnancy

DRUGS

Aminopterin/amethopterin ACE inhibitors Carbamezapine Cocaine Diethylstilbestrol Etretinate/Isotretinoin Lithium Phenobarbital Propylthiouracil Prostaglandins Tetracycline Valproic acid Warfarin (coumadin)

HEAVY METALS

Lead, Mercury

RECOGNIZED HUMAN TERATOGENS

MATERNAL CONDITIONS

Alcoholism (alcohol) Diabetes Smoker (cigarettes) Autoimmune Diesase (Lupus)

INTRAUTERINE INFECTIONS

Cytomegalovirus (CMV) Herpes Simplex (HSV) HIV Parvovirus (Fifth’s Disease) Rubella (German Measles) Toxoplasmosis Varicella (Chickenpox)

OTHER

Inhalants (toluene)

∗ Reflective Listening/Build Rapport

∗ Comprehensive Pregnancy Checklist

∗ Conversation/Providing Information/Principles of Teratology Genetic Susceptibility Who’s more sensitive?

Time of Exposure When was it taken?

Dose-Response Relationship How much was taken?

Bioavailabilty of Agents How much gets to the fetus matters?

Mechanism/Pathogenesis How does it affect the development

Range of Outcomes How severe are the effects?

How does MTBCa “work” with Pregnant and Breastfeeding moms?

Proposition 65 WARNING

∗Caffeine Does not appear to increase the risk for birth defects.

Conflicting data on whether high daily doses of caffeine cause an increased risk of miscarriage or a decrease in birth weight

Studies suggest adverse effects above 200-300 mg/d (equivalent to about 2-3 cups of coffee or 4-6 cans of cola); dose above which toxicity may occur.

ACOG: Moderate caffeine consumption (less than 200 mg per day) does not appear to be a major contributing factor in miscarriage or preterm birth.

Caffeine

Category A: Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and no evidence of a risk in later trimesters), and possibility of fetal harm appears remote. Category B: Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).

Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Category D: There is positive evidence of human fetal risk, bit the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Category X: Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the dug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

FDA Pregnancy Drug Labeling

Statins - 1st trimester exposure

∗Classified as pregnancy category X; Contraindicated primarily due to the fact that cholesterol is essential for normal fetal development

∗ Increasingly used in women of reproductive age, so inadvertent exposure in unplanned pregnancy occurs

∗ Initial concerns in humans raised by review of FDA Adverse Event Reports; 214 cases of 1st-trimester statin exposure reported between 1987 and 2001; 70 were evaluable

∗Review of 31 infants with defects suggested excess of CNS defects (holoprosencephaly), limb reduction defects, and possible VACTERL association Edison & Muenke, Am J Med Genetics, 2004

Statins - 1st trimester exposure (cont)

∗ Canadian database study (1997 – 2003); Group A (64 infants): mothers had filled a prescription for statin before or during the 1st trimester, Group B (14 infants) mother filled a prescription for fibrates or nicotinic acid, and Group C (67 infants) mothers filled statin Rx > 1 year before pregnancy. No increase or specific pattern of malformations was seen. Ofori et al, British J Clin Pharm 2007

∗ Pharmacovigilance data from Merck; 225 prospective reports with outcome. 3.8% rate of major malformations and no specific pattern or similarities to the FDA case series. Pollack et al, Birth Defects Research (Part A) 2008

∗ Case series of 22 malformed infants with prenatal statin exposure from National Birth Defects Prevention Study and Slone Epidemiology Birth Defects Study 1997 - 2006. No VACTERL, holoprosencephaly or limb reduction defects reported. Peterson et al, Am J of Med Genet Part A, 2008

Testosterone

Courtesy of T. Ernesto Figueroa

Testosterone

∗ Endogenous testosterone: important for sexual maturation at all stages of development throughout life

∗ FDA-approved in 1939. Synthetically, prepared from cholesterol.

∗ Testosterone is contraindicated during pregnancy because of probable adverse effects on the fetus (FDA pregnancy risk category X). Women of childbearing potential who are receiving testosterone treatments should utilize adequate contraception.

∗ OCP; Infertility treatment - ovarian stimulation; studies have shown testosterone concentration being significantly elevated in pregnant women

∗ Testosterone in male embryos important for differentiation of the genitalia

∗ Masculinization of the external genitalia of a female fetus has been associated with excessive endogenous testosterone

Mental Health Illnesses: Depression, Bipolar Disorder, Anxiety, etc.

Selective Serotonin Re-uptake Inhibitors (SSRIs)

Conflicting data on risk for major congenital anomalies

A small absolute risk, (if any), for major anomalies, mostly cardiovascular, especially with paroxetine cannot be excluded

The untreated underlying condition carries a risk for preterm delivery

Neonates of mothers treated with SSRIs should be closely followed up after delivery

Risks/benefits for mother/child: optimum for both

Mental Health co-morbidities (modifiable)

Smoking

Overweight or obesity

Poor nutrition, lack of exercise

Substance abuse; Other drug use/alcohol use

Poor uptake/access to adequate prenatal care

Failure to take folic acid supplements prior to becoming pregnant and throughout pregnancy

SUBSTANCE (or Rx drugs of) ABUSE

∗ Alcohol

∗ Cigarettes (nicotine)

∗ Marijuana

∗ Cocaine

∗ Methamphetamine

∗ Ecstasy/MDMA

∗ Heroin

∗ Oxycodone (Oxycontin)

∗ Propoxyphene (Darvon)

∗ Hydrocodone (Vicodin)

∗ Pentobarbital (Nembutal)

∗ Diazepam (Valium)

∗ Alprazolam (Xanax)

∗ Dextroamphetamine (Dexedrine)

∗ Methylphenidate (Ritalin)

How to get drunk without drinking

Features of Fetal Alcohol Syndrome (FAS)

Risky Drinking

BINGE 5 or more alcohol drinks on 1 day; could be most harmful to the baby

MODERATE 2-4 alcohol drinks every day in the 1st trimester; 11 % risk of FAS

CHRONIC 4-8 alcohol drinks every day and/or throughout pregnancy; 44 – 50% risk of FAS

Fetal Alcohol Syndrome (FAS) causes more birth defects in the U.S. than any other known teratogen;

#1 cause of PREVENTABLE mental retardation in the U.S.

1 in 30 women who know they are pregnant report “risky drinking”

Variation of Palmar Creases

∗ Simian Crease ∗ Single transverse palmar crease ∗ 50 % of people with Down Syndrome ∗ Found in 10% of the general population

∗ Hockey-Stick palmar crease ∗ Typically seen in people with Fetal Alcohol Syndrome. ∗ Found in 10% of the general population

∗ Specific pattern of malformation established ∗ Animal models have added substantial new information to our

understanding of this disorder ∗ Risk factors identified

Maternal age >30 years Lower socioeconomic group Ethnic group Previous child with FAS Maternal under-nutrition Genetic background

∗ A number of neurobehavioral abnormalities elucidated

Alcohol and Pregnancy: What Have We Learned in 37 Years?

∗ Reduced IQ (average in low 70s); Developmental delays ∗ Problems with attention (sustained attention and shifting of attention);

Increased reactivity and activity ∗ Executive functioning deficits (e.g. Impaired planning, concept formation) ∗ Learning and memory deficits, including problems with habituation, spatial

memory ∗ Poor fine and gross motor skills; Sensory integration problems; Hearing

abnormalities; ∗ Perseverative (may repeat errors, have difficulty changing from doing things

one way to another) ∗ Feeding deficits; Poor state regulation ∗ Immature social behaviors

Fetal Alcohol Syndrome Neurobehavioral Abnormalities

∗ Prospective observational follow-up; NOT A CLINICAL TRIAL! ∗ Information collected Name of Exposure/agent Exposure Dose and when taken in pregnancy Potential Confounders

∗ Relatively low lost to follow-up (LTFU) ∗ Evaluation of a Range of Outcomes Pattern of major and minor malformation (Home Visit) Adverse Pregnancy Outcome (i.e. Growth Deficiency, Miscarriages) Neurodevelopmental evaluation (California residents)

MotherToBaby California Mom-Baby Follow-up Program

MotherToBaby California Working Conceptual Model

Prospective ascertainment of pregnant women

Telephone Call * eMail * Online Chat MotherToBaby CALIFORNIA

Provide Information/Counseling

Callback Discuss Mother/Baby Follow-up

Program Enrollment

MotherToBaby California

MotherToBaby/

OTIS Pregnancy Studies

∗ OTIS: Organization of Teratology Information Specialists ∗ A non-profit organization made up of individual members

working or involved with a Teratogen Service in North America. ∗ Provide accurate evidence-based, clinical information to

patients and health care professionals about exposures during pregnancy and lactation.

∗ For questions call 866-626-6847

Who is MotherToBaby/OTIS?

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Vaccines and Medications in Pregnancy Surveillance Systems (VAMPSS)

∗ New Network To Track Drugs and Vaccines in Pregnancy

∗ American Academy of Allergy, Asthma and Immunology Organization of Teratology Information Specialist (OTIS) Slone Epidemiology Center

∗ Federal Fund Agency for Healthcare Research and Quality (AHRQ) Biomedical Advanced Research and Developmental Authority (BARDA)

∗ Advisory Committee Center for Disease Control (CDC) Obstetrics and Pediatric Groups

Risk Perception

Promote a Healthier Pregnancy and Babies!

As one inhales through the hose, air is pulled through the charcoal and into the bowl holding the tobacco; Smoke is passed through a water basin (often glass based) before inhalation.

2005 WHO report states that smoking using a waterpipe poses a serious potential health hazard and is not a safe alternative to cigarette smoking.

Smoke from a waterpipe contains high levels of toxic chemicals, including high levels of carbon monoxide, metals and cancer-causing chemicals

Hookah is single or multi-stemmed instrument for smoking flavored tobacco called Mu‘assel; Also know as a waterpipe, arghile, or qalyān

∗ e-cigarettes work basically the same way; Battery-operated heating element ∗ A nicotine cartridge, other liquids, flavorings; Levels of dangerous chemicals they give off are a fraction of what you'd get from a real cigarette ∗ Not regulated by the FDA contents can vary.

Smoking & Lactation

Alcohol (ethanol) and Lactation

Alcohol (ethanol) and Lactation

∗ Maternal alcohol (ethanol) ingestion during lactation: (1) complex and (2) depend on the pattern of maternal drinking.

∗ Breastmilk alcohol levels closely parallel blood alcohol levels. Highest levels in milk - 30 to 60 minutes after drinking; food delays the time of peak milk alcohol levels.

∗ Nursing after 1 or 2 drinks (including beer) can decrease the infant's milk intake by 20 to 23% and cause infant agitation and poor sleep patterns. Long-term effects of daily alcohol use on the infant are unclear

∗ Decreases milk production with 5 drinks or more; decreases milk letdown; disrupts nursing until maternal alcohol levels decrease.

∗ Beer may increase serum prolactin levels during nursing because of polysaccharides from barley and hops.

∗ Women with a family history of alcoholism have a blunted prolactin response following breast stimulation and tend to breastfeed more frequently to compensate.

Alcohol (ethanol) and Lactation

Some study show infant growth and motor function negatively affected by 1 drink or more daily, but other studies have not confirmed these findings.

Heavy maternal use may cause excessive sedation, fluid retention, and hormone imbalances in breastfed infants.

Casual use of alcohol (such as 1 glass of wine or beer per day) is unlikely to cause either short- or long-term problems in the nursing infant, especially if the mother waits 2 to 2.5 hours per drink before nursing, and does not appear to affect breastfeeding duration.

Daily heavy use of alcohol (more than 2 drinks daily) may affect infants negatively and appears to decrease the length of time that mothers breastfeed their infants.

Nursing or pumping within 1 hour before ingesting alcohol may slightly reduce the subsequent amounts of alcohol in breastmilk.

∗ We care about moms and their babies ∗ More than 100,000 women trust and call MotherToBaby affiliates every

year to get answers ∗ Moms might have questions about over-the-counter medications she

might have taken or would like to take ∗ Moms might have been sick or have a chronic illness and want to know

how her condition or medication might affect her baby ∗ Moms might have had some alcohol to drink early in pregnancy and

have questions

Why call MotherToBaby California

∗ Reduce calls to clinics ∗ Support physician care plan ∗ Clarify misconceptions, allay fears and reduce anxiety ∗ Discuss appropriate prenatal testing and specialist

referrals ∗ Promote Healthy Behavioral Choices ∗ Preserve wanted pregnancies

MotherToBaby Ca ~ Benefits for the Public and Health Professionals

Fact sheets

Fact Sheet (downloadable)

Another Healthy Baby

planning a pregnancy . pregnant . breastfeeding

MotherToBabyCA.org Toll FREE 866.626.6847