objectives communicating risk in pregnancy - ucsf absolute risks of stillbirth if go to sleep on:...

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“Can I do this while I’m pregnant?”

Searching for EvidenceBehind Pregnancy Advice

Robyn Lamar, MD, MPHAssistant Professor,

Obstetrics & Gynecology at UCSF

Disclosures• I have nothing to disclose

Objectives• Consider how we discuss risk related to

lifestyle choices in pregnancy• Evaluate pregnancy related advice concerning:

– seafood– sleep position– caffeine– alcohol

Communicating Risk in Pregnancy

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Laundry list? Public Health Campaign Poster?

Economics-style Risk-Benefit Analysis? Medical Ethics framework?

• Ethical principles:– Autonomy– Beneficence & nonmaleficence– Justice

Ethical Decision Making in Obstetrics andGynecology*

Number 390 • December 2007

A C O G C O M M IT T E E O P IN IO N

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Communicating Risk in Pregnancy:Common pitfalls

1 Falsely dichotomizing a range of risk into “low risk” and “high risk” exposures

2 Letting any risk to the fetus trump considerations related to the wellbeing of the pregnant woman

3 Emphasizing the risks of taking certain actions, but ignoring the risks of avoiding those actions

Lyerly, A. D. et al. Risks, values, and decision making surrounding pregnancy. Obstet Gynecol 109, 979–84 (2007).

Decision-making in pregnancy• Pregnant women deserve care that is both

evidence-based and patient- centered. • We should avoid reinforcing distortions of risk • We can do this by:

– acknowledging the range of values that pregnant women bring to decisions

– Identifying a range of well-considered options and allowing women to make decisions in the context of their own priorities and life circumstances


Case Examples

Can I eat seafood?

Retrieved from: http://www.montereyfish.com/

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Seafood: Official AdviceACOG: “pregnant women . . . should eat at least 8 and up to 12 ounces per week of a variety of fish lower in mercury.”

ACOG Practice Advisory: Seafood Consumption During Pregnancy

Seafood in PregnancySeveral issues to consider:• From nutrition standpoint: high protein, low

fat, high in DHA• From contamination standpoint: mercury

levels, other pollutants• From food safety perspective: contamination

risk if raw/undercooked?

Seafood: History2001 FDA Advisory

• Don’t eat 4 fish high in mercury– Shark– Tilefish– King mackerel– swordfish

• Limit overall fish consumption to 12oz/week

Seafood: Early Evidence1990s: cohort studies published in • Faroe islands• New Zealand Correlated increasing levels of mercury in mother’s hair & decrements in child’s language skills, memory, motor speed, and visuospatial function

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Seafood: Early Evidence

– Unusual consumption patterns (Faroe islands: pilot whale meat/blubber; NZ shark)

– Reanalysis looking at seafood consumption itself (not mercury level) did NOT show link

Seafood: Seychelles Cohort study

Davidson P, Cory-Slechta D, Thurston S, et al. Fish consumption and prenatal methylmercury exposure: Cognitive and behavioral outcomes in the main cohort at 17 years from the Seychelles child development study. NeuroToxicology 2011;32(6):711717.

Seafood: Seychelles Cohort study• High fish diet (12 servings/wk), no

consumption of marine mammals/shark• Predictor variable: maternal hair mercury• Outcome variables: neurocognitive &

behavioral testing done from age 6mo – 17yo• Results: as maternal mercury increases . . .

– 26 of 27 outcomes: no difference or better scores– 1 of 27 outcomes: Higher risk of referral to school

counselorDavidson P, Cory-Slechta D, Thurston S, et al. Fish consumption and prenatal methylmercury exposure: Cognitive and behavioral

outcomes in the main cohort at 17 years from the Seychelles child development study. NeuroToxicology 2011;32(6):711717.

Seafood: Systematic Review of prenatal fish & neurodevelopment

• 8 cohort studies identified– Published between 2000-2014– Predictor variable: maternal seafood consumption– Evaluated offspring from age 3 days – 9 years– Sample sizes ranged from 135 to over 25,000

• Findings– One study showed no association– 7 studies showed improved outcomes as maternal

seafood consumption increasedStarling P, Charlton K, McMahon AT, Lucas C. Fish intake during pregnancy and foetal neurodevelopment--a systematic review of the

evidence. Nutrients 2015;7(3):2001–14.

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Seafood: Current Consumption

None20%

less than 2 oz40%

2 to 4oz20%

4+ oz20%

Seafood consumption in last week among 1000 Pregnant Women

S Ostroff. (2014, June 10). Why We Want Pregnant Women and Children to Eat More Fish. Retrieved from http://blogs.fda.gov/fdavoice/index.php/tag/environmental-protection-agency-and-food-and-drug-administration-advice-about-eating-fish/

The women in the highest consumption category aren’t necessarily even eating 1 serving a week!





Lyerly, A. D. et al. Risks, values, and decision making surrounding pregnancy. Obstet Gynecol 109, 979–84 (2007). Retrieved from: https://www.washingtonpost.com/national/health-science/2012/04/03/gIQABd16sS_graphic.html

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This looks complicated.Should I just take fish oil instead?

Fish Oil: EvidenceRecent Meta-analysis looked at omega-3 supplementation during pregnancy & childhood neurodevelopment• 11 RCTs with 5,272 participants• No difference in cognitive, language, or motor

development– Except for cognitive scores in subgroup of 2-5 year

olds; but driven by 2 studies rated high risk for bias

Gould J, Smithers L, Makrides M. The effect of maternal omega-3 (n-3) LCPUFA supplementation during pregnancy on early childhood cognitive and visual development: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr.

2013;97(3):531–44. doi:10.3945/ajcn.112.045781.

OK, I’ll eat fish. What about sushi?

Raw Seafood: Advice• ACOG says no• NHS says raw fish is fine, if frozen first

– Deep freezing kills parasites (anasakis, tapeworm)– FDA requires freezing fish intended to be eaten raw

• Seafood causes a tiny percent of food poisoning in the US

• Raw shellfish is responsible for the vast majority of seafood-associated “food poisoning” – can be contaminated with vibrio cholera or norovirus

“Seafood Choices: Balancing Benefits and Risks.” IOM report brief, Oct 2006.http://www.nhs.uk/chq/pages/is-it-safe-to-eat-sushi-during-pregnancy.aspx?categoryid=54

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Seafood: Summary• Eat seafood• Not too much, but not too little• Eat some types, but not others• Cook shellfish thoroughly• Enjoy fish if it’s been well frozen

. . . Is it any wonder women give up?

Can I sleep on my back?

Sleep Position: The Official advice

About 1,560,000 results (0.59 seconds)

Feedback

The best sleep position during pregnancy is “SOS” (sleep on side).Even better is to sleep on your left side. Sleeping on your left side willincrease the amount of blood and nutrients that reach the placenta andyour baby. Keep your legs and knees bent, and put a pillow betweenyour legs.

Sleeping Positions During Pregnancyamericanpregnancy.org/pregnancy.../sleeping-positions-during-pregnancy/

Web Images Videos News Shopping Search toolsMore

sleep position while pregnant

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Sleep Position• Theory: simple & compelling

– As uterus enlarges, supine position causes compression of vena cava, decreasing venous return & cardiac output

– Familiar practice for c/s & ACLS in pregnancy, and to ameliorate fetal heart tracing changes

• Evidence: limited

Sleep Position: Stacey et al2011 prospective case-control study in New Zealand• Cases: 155 singletons with 3rd tri stillbirth• Controls: 301 ongoing singleton pregnancies matched

for GA• Results: OR for stillbirth

– Supine vs left: 2.54– Nocturia once or less vs more: 2.28– Daytime napping vs not: 2.04

• Absolute risks of stillbirth if go to sleep on:– Left 1.96/1000– Back or right 3.93/1000

Sleep Position: Stacey et al• Some things to consider about Stacey’s study:

– Recall bias? • Controls were asked about last night’s sleep• Cases interviewed an average of 25 days after delivery

– Reverse causality?• Before pregnancy, cases & controls equally likely to

sleep on their back, left, or right sides• “What would reduce normal progression toward the

preference of a more lateral tilt, [and] reduce the need to go to the bathroom at night?”

IUGR?Froen JF et al. “No need to worry about sleeping position in pregnancy—quite yet.” BMJ 2011;342;d3404

Sleep Position & IUGR: Theories• So is supine sleep part of the “triple risk” that

increases stillbirth?– 1: maternal risk factors (obesity, smoking, age)– 2: fetal & placenta risk factors (IUGR)– 3: stressor (sleeping position?)

• Or is IUGR actually the real risk factor that leads to both supine sleep & stillbirth?

Stacey T, Thompson JM, Mitchell EA, Ekeroma AJ, Zuccollo JM, McCowan LM. Association between maternal sleep practices and risk of late stillbirth: a case-control study. BMJ. 2011 Jun 14;342:d3403.

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Sleep Position: Owusu et al2013 Cross-sectional study looking at sleep practices & pregnancy outcomes (birthweight preeclampsia, etc) among 234 women in Ghana• Results:

– Supine sleep as a risk for IUFD:• OR adjusted for maternal factors: 8.0 (1.5-43)• OR also adjusted for IUGR: 4.9 (0.8-34)

– Percent of women who slept supine at term:• Low birthweight: 25%• Normal birthweight: 6%

Owusu JT, Anderson FJ, Coleman J, et al. Association of maternal sleep practices with pre-eclampsia, low birth weight, and stillbirthamong Ghanaian women. Int J Gynaecol Obstet 2013;121(3):261–5

Sleep Position: Sydney Stillbirth Study2015 prospective case-control study in Australia• Cases: 103 singletons with 3rd tri stillbirth• Controls: 192 singletons matched for GA• Asked about “usual” sleep position in last month• Results for supine sleep: aOR 6.26 (1.2-34)• Of the 10 stillbirths among back sleepers, none

was classified as “unexplained”• Infection (3), hemorrhage (1), PPROM (1), IUGR (3), maternal

condition (2)Gordon A, Raynes-Greenow C, Bond D, Morris J, Rawlinson W, Jeffery H. Sleep position, fetal growth restriction, and late-pregnancy

stillbirth: the Sydney stillbirth study. Obstet Gynecol 2015;125(2):347–55.

Sleep Position: UpcomingOngoing research study:

MiNESS(Midland and North of England Stillbirth study)

• larger case control-study• powered to detect interaction between

variables (i.e., IUGR & sleeping position)

Sleep Position: SummaryWomen who sleep on their back in the 3rd

trimester have a higher risk of stillbirthBut . . . .• Few women with normal size bellies go to

sleep on their back in the 3rd trimester• If there is an attributable risk from supine

sleeping, the absolute value is very smallGet sleep as you’re able in the 3rd trimester!

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When you were pregnant, did you drink coffee?

A. NeverB. OccasionallyC. 1-2 cups a day on averageD. More than 2 cups a day on

average

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Coffee: The Official Advice• ACOG: “Moderate caffeine consumption (less

than 200 mg per day) does not appear to be a major contributing factor in miscarriage or preterm birth. The relationship of caffeine to growth restriction remains undetermined.”

• Other societies: less than 200-300mg/day

ACOG CommitteeOpinion No. 462: Moderate caffeine consumption during pregnancy.

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Coffee: Research Challenges• American women who drink coffee are:

– Older– More likely to smoke & drink– Less healthy conscious– Lower SES

• “Pregnancy signal” hypothesis: bad nausea is correlated with lower risk of miscarriage, but amy lead to aversion to coffee

Coffee: IUGR EvidenceBech et al: sole RCT regarding coffee intake• Double blind, controlled trial of 1207 women

drinking 3+ cups of coffee/day in 2nd tri• Design: randomized to either decaf or regular

instant coffee at 20wk of pregnancy• Results: (for caffeinated vs decaf groups)

– Dropout rates similar (5 vs 8%)– Mean caffeine intake differed (117mg vs 317mg)– Absolutely no difference in birthweight or GA

Bech BH, Obel C, Henriksen TB, Olsen J. Effect of reducing caffeine intake on birth weight and length of gestation: randomisedcontrolled trial. BMJ 2007

Coffee: IUGR EvidenceSystematic review & meta-analysis 2014• Risk of low birthweight:

Caffeine consumption RR• Low (50-149mg) 1.13 (1.06, 1.21)• Moderate (150-349mg) 1.38 (1.18, 1.62)• High (≥350mg) 1.60 (1.24, 2.08)

• Absolute birthweight difference in grams was small• Low (50-149mg) -9 (-35, 16)• Moderate (150-349mg) -33 (-63, -4)• High (≥350mg) -69 (-102, -35)

• The better the study design (larger; cohort; European?) the smaller the effect (RR ~1.1 vs 1.2-1.3)

Chen L-W, Wu Y, Neelakantan N, Chong M, Pan A, van Dam R. Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose–response meta-analysis. BMC Med 2014;12(1):174

Coffee: SAB evidenceBrent et al. systematic review of studies since 2000• Human data: 17 studies

– Most showed no increased risk for <300mg/day– Those that did often had incomplete control of

confounders (ex: 11/17 did not control for nausea)• Animal data: no increased risk of SAB until levels

well above usual human consumption (i.e., more than 10 cups/day), and even then risk was small

Brent R, Christian M, Diener R. Evaluation of the reproductive and developmental risks of caffeine. Birth Defects Research Part B: Developmental and Reproductive Toxicology 2011;92(2):152–87.

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Caffeine: Unique EvidenceDanish National Birth Cohort study • periconception use of Letigen (ephedrine + 600mg caffeine)

• Result:– Maternal age adjusted HR for SAB = 1.1 (0.8, 1.6)

Klebanoff MA, Levine RJ, DerSimonian R, Clemens JD, Wilkins DG. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. New England Journal of Medicine [Internet] 1999;341(22):1639–44.

Can I drink coffee?• Yes, enjoy your coffee . . . If you’re able

Can I drink a glass of wine? When you were pregnant, did you drink alcohol?

A. NeverB. I had 1 drink a few times during the

pregnancyC. I had 1 drink a few times a monthD. I had 1 drink a few times a weekE. More than that

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Alcohol: Official Advice• ACOG: “no safe level of alcohol use during

pregnancy.”• NICE: none in the 1st trimester, and no more than

1-2 units, 1-2 times a week after that• SOGC: “Abstinence is the prudent choice,” but

“there is insufficient evidence regarding . . . harm at low levels of alcohol consumption.”

• Australia: in 2009 reverted to abstinence messaging after 8 years of saying small amounts were ok

Alcohol: Teratogenicity• FAS is common & likely underdiagnosed:

Study of 1st graders with active ascertainment:– FAS 6-9 per 1000– Partial FAS 11-17 per 1000– FASC 24-48 per 1000

• Drinking among US women age 18-44 is common:In last month . . . Used alcohol: Binged:

– Non-pregnant: 52% 15%– Pregnant: 7.6% 1.4%May PA et al. Prevalence and characteristics of fetal alcohol spectrum disorders. Pediatrics. 2014 Nov;134(5):855-66.

MMWR. Alcohol Use and Binge Drinking Among Women of Childbearing Age — United States, 2006–2010

Alcohol: the dilemma• Challenging to research

– American women who drink in pregnancy are much more likely to smoke & use drugs

• Unclear how drinking amount, pattern, nutrition, and genetics interact to produce FAS in some cases but not others

Despite this, data regarding impact of light to moderate drinking on the fetus is largely reassuring

Alcohol: Recent EvidenceIn September 2012, BJOG published 5 articles from the same prospective cohort study examining alcohol & neurodevelopmental outcomes in young children

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Alcohol: Cohort StudyThe Lifestyle During Pregnancy Study (LDPS): prospective cohort study, sampled from the larger Danish National Birth Cohort (>100,000)• Of note: some alcohol consumption during pregnancy was

considered acceptable to Danish women at that time• Design: recruited 1617 women, sampled to represent 20

different drinking patterns– Phone interview at 12 & 30wk to ascertain weekly alcohol

intake, and any binge (5+) drinking– Controlled for smoking, diet, SES, maternal IQ, medical &

obstetric history– Assess cognitive, behavioral, emotional & social functions in

children at age 5Kesmodel US et al. Lifestyle during pregnancy: neurodevelopmental effects at 5 years of age. The design and implementation of a

prospective follow-up study. Scand J Public Health 2010;38(2):208–19Kesmodel U, Kesmodel PS. Drinking during pregnancy: attitudes and knowledge among pregnant Danish women, 1998

Alcohol: LDPS ResultsAll results are based on assessment

of children at age 5

LDPS Results: IntelligenceOutcome measure: IQ assessed with the Wechsler Primary and Preschool Scales of Intelligence• By average number of drinks per week:

– 1-4, or 5-8 drinks: no difference by any analysis• Mean IQ of 106 or 104, versus 105 in nondrinkers• No higher risk of low IQ (OR 0.9-1.1)

– 9+ drinks: • Mean IQ of 99 (not statistically significant from 105)• Higher risk of low IQ (OR 4.6)

• By binge drinking: – no differences except that binge drinking at GA 1-2wk

reduced risk of low IQ (OR 0.5)Eriksen H, Mortensen, Kilburn, et al. The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5-year-old

children. BJOG 2012;119(10):1191–200.Kesmodel, Eriksen H, Underbjerg, et al. The effect of alcohol binge drinking in early pregnancy on general intelligence in children. BJOG

2012;119(10):1222–31.

LDPS Results: AttentionAttention was measured using the recently developedTest of Everyday Attention for Children at Five Average attention score = 0, higher is better• By average number of drinks per week:

– 1-4, or 5-8 drinks: no difference by any analysis• Mean score difference: (+0.03 and +0.03)• No higher risk of low score (OR 1.17, and 1.37)

– 9+ drinks: • Mean score difference of -0.45 (-1.08, 0.18)• Higher risk of low score, OR 3.2 (1.08, 9.53)

• By binge drinking: – no differences on any measures

Eriksen H, Mortensen, Kilburn, et al. The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5-year-oldchildren. BJOG 2012;119(10):1191–200.

Kesmodel, Eriksen H, Underbjerg, et al. The effect of alcohol binge drinking in early pregnancy on general intelligence in children. BJOG 2012;119(10):1222–31.

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LDPS: Executive FunctionExecutive function assessed using the Behaviour Rating Inventory of Executive Function, an 86-item questionnaire, completed by both a parent & a teacher• No association with any drinking pattern

So can I have a glass of wine? • Public health messaging is a nightmare

– Australia reversed its more lenient stance on alcohol not in the face of new evidence of harm, but due to worries the advice was too confusing

• We’re not all Vikings– variations in genetics and nutrition might leave some

populations more vulnerable to alcohol's harms than others

• Perhaps research is most helpful in reassuring women who inadvertently drank before recognizing pregnancy?






Conclusions

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My Two Cents• Focusing too much on pregnancy taboos:

– Creates an unfounded aura of hazard & mystique around pregnancy

– Distorts perception of risk– Distracts from more important health behaviors– Implies a level of control women may not have

over outcome of their pregnancy

OK, maybe more than 2 cents:• Those laundry lists are likely unavoidable,

given limited visit time• When patients ask what to do when pregnant,

I purposely just focus on healthy living• When they press me on specific issues, I say:

– You can’t make your risk of anything zero– Some risks can be lessened by changing behavior– Changing behavior has its own risks

objectives communicating risk in pregnancy - ucsf absolute risks of stillbirth if go to sleep on:...

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