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The story behind common pregnancy questions

The story behind common pregnancy questions. Angela Hawk MD MFM Fellow 31 May 2014. 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

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The story behind common pregnancy questions

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  1. The story behind common pregnancy questions Angela Hawk MD MFM Fellow 31 May 2014

  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

  3. Black Coffee

  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. Note: some herbals (i.e. guarana) also contain caffeine

  6. January 20, 2008 • The Washington Post: Caffeine Increases Risk of Miscarriage, Study Finds • The New York Times: Study sees caffeine possibly tied to miscarriages • CNN.com: 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

  7. 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

  8. Results • Overall: • 25% (n=264) no caffeine • 60% (n=635) 0-200 mg/day • 15% (n=164) >200mg/day • After controlling for confounders: • 0-200mg no significant risk for SAB (HR=1.42 [0.93-2.15]) • >200mg associated with significant risk for SAB with HR=2.23 (1.34-3.69)

  9. * • 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 • 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

  10. 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

  11. 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 0.7-1.3) • 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

  12. 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

  13. 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

  14. * 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

  15. 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

  16. 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

  17. Blonde Hair

  18. 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.

  19. Human Studies • Some older studies have suggested associations with • Low birth weight (OR 1.36, 95%CI 1.09-1.7) • 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

  20. 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

  21. Human data • Scand J Work Environ Health 2005 (Rylanderet al) • Prospective study from the Swedish Medical Birth Registry • >12,000 infants of hairdressers vs controls (working moms) • Increase in SGA OR 1.19 (1.07-1.33) • 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 vs3513g for controls • Results not very convincing, but even if true, effect is small

  22. 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

  23. 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 WloframLJ et al

  24. 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

  25. Seafood

  26. 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

  27. 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

  28. * Methyl mercury Poisoning • History: • Minamata, Japan: Waste water containing inorganic mercury released into Shiranui Sea between 1932-1966. 18-598 ppm in maternal hair • Iraq: Seed grain incident, 1971. >10-12 ppm • Consequences: • Adults: serious neurologic symptoms & death (parasthesias, ataxia, loss of vision) • Kids exposed in utero: motor/sensory problems, microcephaly, developmental delay

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

  30. 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 0.5-26.7ppm) • Cohort being evaluated @ 16 years of age

  31. 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: 0.17-39.1 ppm)

  32. 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)

  33. * 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

  34. 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 1.16-1.9) • Dose/response curve noted (lower intake=lower scores & higher intake=higher scores) • Results persisted after controlling for 28 confounders

  35. 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

  36. Oken, et al. Study • Prospective cohort study of 341 mother-child pairs in Massachusetts • 2nd 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

  37. 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

  38. 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.”

  39. Q: So, why not just take DHA?

  40. A: Because it probably doesn’t work • Cochrane review, 2006 • 6 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 mospp • No effect on IQ @ 7 y/o • Green J Feb 2010 RCT (Harper) • no difference in PTB among HR women taking 17OHP

  41. 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

  42. …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.

  43. 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.

  44. Sandwiches

  45. Why the debate? Positives: Yummy Negatives: Listeria

  46. 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)

  47. 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

  48. 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

  49. 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%)

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