Transcript 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
• Risk of Listeria from food sources
BLACK COFFEE
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
Item
Caffeine Content
5 oz cup of coffee
40-180mg
5 oz cup of tea
20-90mg
12 oz Coke
46mg
Red Bull energy drink
67mg
1 cup coffee ice cream
58mg
Hershey chocolate Bar
10mg
8 oz hot chocolate
5 mg
2 tablets of Excedrin
130 mg
Note: some herbals (i.e. guarana) also contain caffeine
Study
Association
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)
January 20, 2008
• The Washington Post: Caffeine Increases Risk of Miscarriage,
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•
•
•
•
•
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
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
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 (1.343.69)
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
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
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
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
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
*
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
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
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
BLONDE HAIR
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.
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
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
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 (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 vs 3513g for controls
• Results not very convincing, but even if true, effect is small
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
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
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
SEAFOOD
Why the debate?
Positives:
-contain highquality
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
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
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
*
Dueling Cohorts
• Two studies showing conflicting results published in same
journal in 2006
Republic of Seychelles
Islands
Bottom line:
Fish/Mercury are OK
Davidson et al
VS.
Faroe
Bottom line:
Fish/Mercury are BAD
Debes F et al.
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
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)
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)
*
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
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
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
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
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
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.”
Q: So, why not just take DHA?
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 mos pp
• No effect on IQ @ 7 y/o
• Green J Feb 2010 RCT (Harper)
• no difference in PTB among HR women taking 17OHP
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
…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.
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.
SANDWICHES
Why the debate?
Positives:
Yummy
Negatives:
Listeria
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
(discussion of management outside the scope
talk)
x 2-4w (full
of this
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
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
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%)
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)
Things that are more
common than
pregnancy
complications from
listeria…
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, www.nsc.org
Death by Falling down stairs
1 / 1,300 (lifetime odds)
National Safety Council, www.nsc.org
Serious injury by falling out of bed
1 / 5,508 (lifetime odds)
National Safety Council, www.nsc.org
Things that are less
common than
listeriosis related
pregnancy
complications…
Shark Attack
1 / 11,500,000
University of Florida
International Shark Attack File
Being Struck by Lightening in a given year
1 / 775,000
National Weather Service
“Lightening safety”
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
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
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
References
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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) 55-62.
Bech, Obel, Henricksen, and Olsen. Effect of reducing caffeine intake on birth weight and length of gestation; randomised controlled trial.
BMJ 2007: doi10.1136, 1-6.
Pollack et al. Caffeine consumption and miscarriage: a prospective cohort study. Fert&Sterility 2010; 93, 304-306.
Jahanfar S and Jaafar S. Effects of restricted caffeine intake by mother on fetal, neonatal, and pregnancy outcome. Cochrane collaboration,
Issue 2, 2012.
Hibbeln et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an
observational cohort study. Lancet 2007: 369, 578-585.
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: 1171-81.
Davidson et al. Methylmercury and neurodevelpment: longitudinal analysis of the Seychelles child development cohort. Neurotoxicol Teratol
2006;28:529-35
Debes F et al. Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years. Neurotoxicol Teratol 2006;28:53647.
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 2004.
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 2004. 294-300
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: 1503-9.
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: 17-158.
Lamont et al. Listeriousis in human pregnancy: a systematic review. J Perinat Med 2011; 39, 227-236.
Ogunmodede, F et al. Listeriosis prevention knowledge among pregnant women in the US. Infectious Dis Ob Gyn 2005: 13: 11-15.
Cates et al. Pregnant Women and Listeriousis: preferred educational messages and delivery mechanisms. Journal Nutr Educ Behav 2004;
36: 121-127.
Questions??