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Presentation on theme: "THE STORY BEHIND COMMON PREGNANCY QUESTIONS Angela Hawk MD MFM Fellow 31 May 2014."— Presentation transcript:


2 Objectives Define some common debates Review the data Discuss the recommendations for management and patient counseling Topics of focus: Coffee consumption Hair dye Fish consumption Risk of Listeria from food sources


4 Caffeine Effects 1,3,7-trimethylxanthine Most commonly used psychoactive substance in the world Readily crosses the placenta Clearance may be prolonged in pregnancy Metabolism may be slower in fetus May decrease intervillous placental blood flow via increased catecholamine

5 ItemCaffeine Content 5 oz cup of coffee40-180mg 5 oz cup of tea20-90mg 12 oz Coke46mg Red Bull energy drink67mg 1 cup coffee ice cream58mg Hershey chocolate Bar10mg 8 oz hot chocolate5 mg 2 tablets of Excedrin130 mg Note: some herbals (i.e. guarana) also contain caffeine

6 StudyAssociation Bech et al (AJE 2005)+ (for >4 cups of coffee/d & fetal death) Cnattingius (NEJM 2000)+ (for >500mg/d) Fernandes (Rep Tox 1998)+ (for >150mg/d BUT NOT controlling for confounders!) Klebanoff M (NEJM 1999)+ (for >500mg/d) Wisborn K (BMJ 2003)+ (for >4cups/d & SB) Parazzini (Hum Reprod 1998)+ (for 2-3cups/d) Fenster (Epi 1991)+ (for >300mg/d) Mills (JAMA 1993)-prospective study from 21days post conception - (for SAB, IUGR, microcephaly) Dlugosz et al (Epid 1996)+ (for >3c/d) Fenster et al (Epid 1997)- Srisuphan et al (AJOG 1986)+ (for moderate-heavy consump)

7 January 20, 2008 The Washington Post: Caffeine Increases Risk of Miscarriage, Study Finds The New York Times: Study sees caffeine possibly tied to miscarriages Caffeine may boost miscarriage risk CBS evening news: Study links caffeine to miscarriage risk MSNBC: Coffee habit may hike miscarriage risk Newsweek: Coffee linked to miscarriages BBC: Coffee raises miscarriage risk

8 AJOG 2008 (Weng et al) “Prospective cohort” study of ~2700 women Designed to study effects of magnets on pregnancy Inclusion criteria positive UPT in the Kaiser Permanente during 2 year period English speaking intent to carry to term <15 wks gestation 39% completed in-person interview (median EGA 71d) magnetic field exposure caffeine/other beverage consumption hot tub use demographics pregnancy symptoms

9 Results Overall: 25% (n=264) no caffeine 60% (n=635) mg/day 15% (n=164) >200mg/day After controlling for confounders: 0-200mg no significant risk for SAB (HR=1.42 [ ]) >200mg associated with significant risk for SAB with HR=2.23 ( )

10 Strengths: Cohort design Large sample size Recruitment at early gestational age for identification of SAB Ascertainment of information on pregnancy related symptoms Controlling for confounding Limitations: Recall & Response Bias 59% of subjects had already miscarried at the time of their interview Poor controlling for nausea (yes/no) Women who decreased consumption (even if still >200) NOT at increased risk Low overall response rate 39% Limited numbers *

11 Savitz study (Epi 2008) Published in same month/year as Weng study Didn’t get much press but well done study Prospective multicenter cohort study of >2000 women Inclusion criteria: >18 years old <12 weeks gestation Interviews conducted similar to previous study Similar to Weng study, some women had miscarried before the interview In contrast to the Weng study, the authors controlled for this

12 Results Median caffeine intake 243mg prepregnancy 210mg at 4wks after LMP 144mg at time of telephone interview Among ALL women, coffee and caffeine consumption were unrelated to overall risk of SAB (OR ) Analysis of women who suffered SAB before the interview (n=74), evidence of a positive association between caffeine and SAB BUT analysis of women who suffered losses after the interview (n=184) showed NO association

13 Pollack AZ, et al (Fert Ster 2009) Prospective cohort study aiming to assess caffeine consumption during sensitive windows of development 68 women pre-conception Daily diaries of exposures Caffeine exposure peri-ovulation and peri-implantation NO association between caffeine intake and miscarriage NO association between caffeine and likelihood of becoming pregnant

14 Birth weight & Length of Gestation Bech et al 2007 (BMJ) Randomized double-blind controlled trial (!) 1200 women <20 weeks gestation Minimum intake of 3 cups/day No h/o previous PTB, LBW, other comorbidities Randomized to caffeinated vs decaf coffee at 20w GA (182 mg) No difference in: Primary outcomes: birth weight or length of gestation Secondary outcomes: AC, PI, placenta weight, PTB, SGA, 5 min Apgar <7 In a subset of women who smoked, those randomized to caffeine 263 g less than non-smokers

15 Additive effect of Tobacco + Caffeine? Other studies have suggested a link between smoking and caffeine in relation to birth weight Klebanoff Am J Epi 2002, Cook BMJ 1996, Grosso Am J Epi 2006 May be mediated by cytochrome P450 system Smokers metabolize caffeine faster than non-smokers Paraxanthine (caffeine metabolite) concentration may be related to fetal growth *

16 Cochrane Database Report 2012 “Conflicting results call for properly designed double blind RCTs to establish the possibility of confidently advising women about avoiding caffeine during pregnancy” “Insufficient evidence to evaluate the effect of caffeine on fetal, neonatal and maternal outcomes” RCTs: Difficult to do Need to be started early or even before pregnancy to evaluate all primary outcomes

17 Final Thoughts… Based on the BEST data, caffeine likely contributes little, if at all, SAB PTB In women who smoke, caffeine may play a role in lower birth weight May be prudent, in the face of uncertainty, to limit intake to <300mg/day


19 Animal Studies Some animal studies have suggested teratogenicity but these were conducted at doses that were also toxic to the mother Marks TA, et al.

20 Human Studies Some older studies have suggested associations with Low birth weight (OR 1.36, 95%CI ) SAB Neurodevelopmental outcomes Limited by retrospective nature & lack of controlling for confounding variables Newer studies have not supported these findings Improved research techniques Changes in composition of hair dye

21 Human data Epidemiology 1997 (Kersemaekers WM et al) Historical cohort study in Netherlands 9,000 hairdressers & 9,000 controls No significant difference in SAB LBW prematurity major structural malformations developmental milestones of offspring

22 Human data Scand J Work Environ Health 2005 (Rylander et al) Prospective study from the Swedish Medical Birth Registry >12,000 infants of hairdressers vs controls (working moms) Increase in SGA OR 1.19 ( ) No increase in PTB or malformations Some controlling (smoking, age, parity) but not comprehensive (not maternal BMI, education) Difference in mean birth weight: 3459g for hairdressers vs 3513g for controls Results not very convincing, but even if true, effect is small

23 Human data Obstetrics & Gynecology 2009 (Gallicchio et al) Questionnaire study of 350 cosmetologists and 397 controls Adjustment for confounders (age, race, education, smoking, EtOH), NO significant associations between occupation and pregnancy or child health outcomes Significant differences between groups noted in education, household income, cigarette smoking status, and insurance status Illustrates the importance of controlling for these factors

24 Actual exposure Amount of dye absorbed through the scalp minimal (< 1% of the applied dose) Highlights alone do not even touch the scalp & dye is not absorbed through hair alone  expected to pose no risk Wlofram LJ et al

25 Conclusions Hair treatment in pregnancy unlikely to be of concern Minimal absorption of dye products from routine use For cosmetologists, data does not support substantial risk but any risk may be minimized by: Proper working conditions Well ventilated area Gloves


27 Why the debate? Positives: -contain high- quality protein -are low in saturated fat -are high in omega-3 fatty acids Negatives: Nearly all fish contain traces of mercury which may effect neurodevelopment of the fetus

28 The FDA says (2004)… Avoid shark, swordfish, king mackerel, or tilefish due to high levels of mercury Eat up to 12 oz/340 g (2 average meals) a week of a variety of fish & shellfish Choose fish low in mercury: shrimp, canned light tuna (NOT albacore/white tuna), salmon, pollock, catfish Check local advisories about the safety of fish caught by family & friends Based on a recommended mercury exposure of 1 PPM

29 Methyl mercury Poisoning History: Minamata, Japan: Waste water containing inorganic mercury released into Shiranui Sea between ppm in maternal hair Iraq: Seed grain incident, >10-12 ppm Consequences: Adults: serious neurologic symptoms & death (parasthesias, ataxia, loss of vision) Kids exposed in utero: motor/sensory problems, microcephaly, developmental delay *

30 Dueling Cohorts Two studies showing conflicting results published in same journal in 2006 Republic of Seychelles VS. Faroe Islands Davidson et al Debes F et al. Bottom line: Fish/Mercury are OK Bottom line: Fish/Mercury are BAD

31 Republic of Seychelles Diet contains 10x more fish than average US population Cohort of 700+ kids up to 11y/o Findings: Some early beneficial effects (preschool language) At 11 y/o, NO pattern (positive OR negative) noted with mercury exposure Average 6.8ppm in maternal hair (range ppm) Cohort being 16 years of age

32 Faroe Islands Nordic fishing community with high consumption of pilot whale Cohort of 1022 kids up to 14y/o Findings: Increased exposure correlated with poorer performance on several measures Exposure was correlated with improved performance on one attention test Average 4.21 ppm in maternal hair (range: ppm)

33 What about US population? None of the aforementioned studies/cohorts are applicable to US population They eat A LOT more fish than we do Among US women of childbearing age median levels of mercury in hair are 0.19 ppm overall Children in these cohorts continued to be exposed to higher levels of mercury post-natally Several epidemiologic studies exist in populations more similar to the US population (ALSPAC, Oken)

34 ALSPAC study Avon Longitudinal Study of Parents and Children Longitudinal, cohort study of 12,000 pregnant women Validated food frequency questionnaires (erythrocyte DHA, umbilical cord mercury concentration) Multivariable logistic regression modeling to control for confounders (education, smoking, SES, etc) Compared developmental, behavioral, and cognitive outcomes of children from ages 6mos-8yrs based on maternal fish consumption None Some (1-340g/wk) >340g/week Hibbeln, Lancet 2007 *

35 ALSPAC results Low maternal seafood intake associated with suboptimal outcomes in: fine motor skills communication social development scores Maternal seafood consumption of <340g/week was ass’d with increased risk of lowest quartile for verbal IQ: OR 1.48 (CI ) Dose/response curve noted (lower intake=lower scores & higher intake=higher scores) Results persisted after controlling for 28 confounders

36 ALSPAC conclusions More than 340g was not detrimental More fish = higher developmental scores Less fish = lower developmental scores Risks from loss of nutrients were greater than the risks of harm from exposure to trace contaminants

37 Oken, et al. Study Prospective cohort study of 341 mother-child pairs in Massachusetts 2 nd trimester fish intake assessed with validated questionnaires Assessment of erythrocyte mercury levels Outcome: childhood (3y/o) neurodevelopment testing Multivariable linear regression controlled for confounders Oken, Am J Epid 2008

38 Oken, et al Results Maternal fish intake directly correlated with erythrocyte total mercury Maternal fish intake of >2 servings/week was directly associated with higher neurodevelopment scores within this group, higher mercury levels were associated with lower scores No benefit with fish consumption at or below 2 servings per week

39 Oken study conclusions More fish=higher scores Higher mercury dulled this effect “Maternal consumption of fish lower in mercury and reduced environmental mercury contamination would allow for stronger benefits of fish intake.”

40 Q: So, why not just take DHA?

41 A: Because it probably doesn’t work Cochrane review, trials, 2800 women “There is not enough evidence to support the routine use of marine oil supplements during pregnancy to reduce the risk of pre-eclampsia, preterm birth, low birth weight or small-for-gestational age” Br J Nut 2008 review Supplementation in “high risk” pregnancies Decreased the frequency of PTB <34w but NO CHANGE in PTB <37w, mean birth weight, SGA/IUGR, PIH/PreE, CD, infant hospital stay, NICU admission Pediatrics 2008 RCT Supplementation from 18w GA to 3 mos pp No effect on 7 y/o Green J Feb 2010 RCT (Harper) no difference in PTB among HR women taking 17OHP

42 Bottom Line Fish intake (>2-3 servings per week) is probably good for fetal neurodevelopment Current FDA recommendations may be too conservative and result in women not receiving many of the beneficial effects of fish intake Limit intake of high mercury fish Not enough evidence for routine supplementation with DHA

43 …and while we’re on fish…. Infection by seafood-related pathogens not well studied in pregnancy Generally limited to GI tract The sushi debate: Larger percentage of foodborne illnesses in countries with higher seafood consumption or where seafood traditionally eaten raw 20% foodborne illnesses in Australia related to seafood vs 70% in Japan Most common transmission associated with raw mollusk shellfish – Vibrio parahaemolyticus (V vulnificus, V cholerae) “1/100 chance of infection with a single serving of raw shellfish from approved harvesting site in US” Butt et al, Lancet Inf Dis 2004.

44 Sushi – cont’d Anisakiasis – nematode most commonly associated with consumption of seafood 1000 cases yearly in japan, 50 cases reported to date in US Prevented by adequate cooking (60°C) or freezing (-10° C) of fish Other less common parasites: trematodes, protazoa Methods to decrease contamination Fecal coliform counts Depuration Specialized harvesting (ie younger fish) Eating at “reputable” establishments Butt et al, Lancet Inf Dis 2004.


46 Why the debate? Positives: Yummy Negatives: Listeria

47 Listeriosis—What is it? Listeria monocytogenes (gram + intracellular rod) Symptoms: fever, muscle aches, GI upset Caused by eating contaminated food Disease most severe in people with weakened immune systems (e.g. pregnancy) Occurs 2-14 days after maternal infection Association with: miscarriage/stillbirth PTB neonatal infection (death, sepsis, meningitis) Treated with high dose PCNs or Bactrim x 2-4w (full (discussion of management outside the scope of this talk)

48 How do I prevent it? CDC/FDA recs Do not eat hot dogs, lunch meats, or deli meats unless they are reheated until steaming hot Wash hands/utensils after handling above foods Avoid soft cheeses (feta, Brie, etc) if made with unpasteurized milk Avoid refrigerated pates or meat spreads (canned or shelf stable meat spreads may be eaten) Wash raw vegetables Consume perishable and ready-to-eat foods ASAP Keep fridge at 40°F & freezer at 0° F

49 How great is the risk? Occurs in about 0.7/100,000 people In US: about 2500 people annually become seriously ill from Listeria about 500 of them die Pregnant women are about 20x more likely than other healthy adults to get listeria progesterone mediated down-regulation of cell mediated immunity  more susceptible to intracellular pathogens About 1/3 of cases happen during pregnancy Fetal infection d/t tropism for feto-placental unit

50 Listeriosis Study Group (1986) 1700 cases (total) 450 deaths (total) 27% cases occurred in pregnancy 22% of perinatal cases resulted in SB or NND Do the math=500 perinatal cases; 100 deaths Incidence of perinatal listeriosis was 7.8/100,000 live births (0.0078%)

51 CDC 2007 estimates Total 800 cases 200 in pregnant women Lower incidence than in 1986, same ratios (ie about ¼ of the cases seen were seen during pregnancy) Incidence of listeriosis in the newborn estimated to be 8.6/100,000 (also similar to 1986)

52 Things that are more common than pregnancy complications from listeria…

53 Getting in a car accident on your way to buy deli meet/hot dogs/etc. 1 / 242 (lifetime odds) 2008 traffic fatalities = 39,800 National Safety Council,

54 Death by Falling down stairs 1 / 1,300 (lifetime odds) National Safety Council,

55 Serious injury by falling out of bed 1 / 5,508 (lifetime odds) National Safety Council,

56 Things that are less common than listeriosis related pregnancy complications…

57 Shark Attack 1 / 11,500,000 University of Florida International Shark Attack File

58 Being Struck by Lightening in a given year 1 / 775,000 National Weather Service “Lightening safety”

59 Patient Awareness Infectious Disease in Ob/Gyn 2005 National survey of 400 pregnant women regarding knowledge of listeriosis & its prevention Only 18% had some knowledge of listeriosis 18% reported avoiding deli meats & ready to eat foods 86% reported avoiding unpasteurized dairy products Of those that reported familiarity with listeria 50% learned from their doc/provider 60% saw it in a book or magazine 23% heard about it from friends/family Ogunmodede et al

60 Patient Awareness 2004 Study (Cates et al; J Nutr Educ Behav) Focus groups with pregnant women Few women aware of Listeria Recommended educational materials targeted to pregnant women including risks & prevention Reported that they would prefer to learn about this from their health provider Focus groups with physicians Information about how to prevent Listeriosis was not part of the usual prenatal care

61 Bottom Line Risk of listeria from contaminated food sources is real but rare Patients are generally undereducated about the risk Patients often received information from sources other than health care providers but would prefer to receive information from providers

62 References ACOG Educational Pamphlet “Nutrition During Pregnancy” Weng X, Odouli R, Li D. Maternal caffine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. AJOG 2008: 198: 279e1-279e8. Savitz et al. Caffeine and Miscarriage risk. Epidemiology 2008: 19 (1) Bech, Obel, Henricksen, and Olsen. Effect of reducing caffeine intake on birth weight and length of gestation; randomised controlled trial. BMJ 2007: doi , 1-6. Pollack et al. Caffeine consumption and miscarriage: a prospective cohort study. Fert&Sterility 2010; 93, Jahanfar S and Jaafar S. Effects of restricted caffeine intake by mother on fetal, neonatal, and pregnancy outcome. Cochrane collaboration, Issue 2, Hibbeln et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet 2007: 369, Oken et al. Maternal fish intake during pregnancy, blood mercury levels, and child cognition at age 3 years in a US Cohort. Am J Epidemiology 2008: 167: Davidson et al. Methylmercury and neurodevelpment: longitudinal analysis of the Seychelles child development cohort. Neurotoxicol Teratol 2006;28: Debes F et al. Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years. Neurotoxicol Teratol 2006;28: Butt A, Aldridge K, Sanders C. Infections related to the ingestion of seafood part 1: viral and bacterial infections. The Lancet Infectious Diseases (4). April Butt A, Aldridge K, Sanders C. Infections related to the ingestion of seafood part 2: parasitic infections and food safety.. The Lancet Infectious Diseases (4). April DiNardo JC et al. Teratological assessment of five oxidative hair dyes in the rat. Toxicol Appl Pharmacol 1985 Burnett C et al. Teratology & percutaneous toxicity studies on hair dyes. J Toxicol Environ Health 1976 Marks TA, et al. Teratogenic evaluation of 2-nitro-p-phenylenediamine, 4-nitro-o-phenylenediamine, and 2,5-toluenediamine sulfate in the mouse. Teratology 1981) Jackson, Iwamoto, Swerdlow. Pregnancy-associated listeriosis. Epidemiolog Infect 2010; 138: DiNardo JC et al. Teratological assessment of five oxidative hair dyes in the rat. Toxicol Appl Pharmacol 1985 Wolfram LJ et al. Percutaneous penetration of hair dyes. Arch Dermatol Res 1985 Janakiraman, V. Listeriosis in Pregnancy: Diagnosis, Treatment, and Preventin. Reviews in Obstetrics and Gynecology 2008: 1: Lamont et al. Listeriousis in human pregnancy: a systematic review. J Perinat Med 2011; 39, Ogunmodede, F et al. Listeriosis prevention knowledge among pregnant women in the US. Infectious Dis Ob Gyn 2005: 13: Cates et al. Pregnant Women and Listeriousis: preferred educational messages and delivery mechanisms. Journal Nutr Educ Behav 2004; 36:

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