Macronutrients in Pregnancy2011

• Carbohydrate• Protein• Lipids

2002 DRI for Carbohydrate

• DRIs for carbohydrate based on brain glucose utilization

• RDA for adults and children = 130 g/day

• Median intake ~:– Men: 200-330 g/day– Women: 180-230 g/day

2002 DRI for Carbohydrate in Pregnancy

• Fetal brain needs a minimum of 33 g/day• EAR for pregnancy (all ages) = 135 g/day• RDA for pregnancy (all ages) = 175 g/day

– CV is 15% based on variations in brain glucose utilization

– RDA = EAR plus twice CV

EAR: Estimated Average Requirement

CV: coefficient of variation (used when insufficient data to determine standard deviation)

2002 DRI for Fiber in Pregnancy

• “There is no evidence to suggest the beneficial effects of fiber in reducing risk of CHD is different from non-pregnant adolescent girls and women.”

• AI = 28 g/day (14 g/1,000 kcal x median kcal intake for group)

• AI for non-pregnant women is 25 g/day

Emerging Issue: Glycemic Index & Pregnancy

Effect of a low-glycemic-index diet during pregnancy on obstetric outcomes

(Moses et al. AJCN 2006)

• 62 women randomized to counseling to promote low GI (LGI) or moderate/high GI (HGI)

• Outcomes for HGI diet:– Higher birthweight (3408 vs 3644)– Higher prevalence LGA (3% vs 33%)

• Conclusion: “Because birth weight and ponderal index may predict chronic disease in later life, a low-GI diet may favorably influence long-term outcomes.”

Dietary fiber intake, dietary glycemic load, and

the risk for gestational diabetes mellitus Zhange et al. Diabetes Care, 2006

• Examined prepregnancy diet in the Nurses Health study (758 pregnancies in 13,110 women over 8 years), adjusted for age, parity, prepregnancy BMI, and other covariates

• Results– Each 10-g/day increment in total fiber intake was associated

with 26% (95% CI 9-49) reduction in risk of GDM – Each 5-g/day increment in cereal or fruit fiber was

associated with a 23% (9-36) or 26% (5-42) reduction, respectively.

– Dietary glycemic load was positively related to GDM risk. Multivariate relative risk for highest versus lowest quintiles was 1.61 (1.02-2.53) (P for trend 0.03).

The dietary glycemic index during pregnancy: influence on infant birth weight, fetal growth, and biomarkers of carbohydrate metabolism

Scholl et al, Am J Epi, 2004) • n=1082, very low income, mostly young,

ethnic minorities in Camden NJ

• women with a dietary glycemic index in the lowest quintile had approximately a twofold increased risk of bearing a growth-restricted infant compared to middle quintile: AOR = 1.75 (1.10, 2.77)

Dietary advice in pregnancy for preventing gestational diabetes mellitus (Cochrane, 2008)

• Three trials, 107 women. • “While a low glycaemic index diet was seen to

be beneficial for some outcomes for both mother and child, results from the review were inconclusive”

• “No conclusions could be drawn from the high-fibre versus control-diet comparison since the trial involved did not report on many of the outcomes we prespecified”

2002 RDA

EAR for Protein in Pregnancy

• EAR = 21 g/day above protein needs at prepregnancy weight

• EAR Per kg– Increased amount on a per kg basis is 0.22

g/protein/kg/day– EAR for non-pregnant = 0.66 g protein/kg

per day– EAR for pregnancy = 0.88 g/kg/day

RDA for Protein for Pregnancy

• 1.1 g/kg/day or 25 g/day additional protein (EAR plus allowance for individual variation)

• RDA for women aged 19-50 is 46 g/day

• RDA is 71g protein per day

Reference woman is 57 kg

RDA to Diet

• RDAs calculated using high quality reference proteins like egg, meat, milk or fish

• However, even with adjustments for lower quality proteins most women in the US who are meeting energy needs with reasonable food choices, will meet protein needs. – Range in US is 75 to 110 g per day for women.

Vegan Diet & Protein Intake

Food Gprotein

#servings

Total gprotein

Totalkcal

Grains 3 11 33 880

Vegetables 4 2 8 100

Beans 15 2 cups 30 550

Total 71 1450

Energy and Protein

• If energy needs are not met by diet then protein will be used for energy

• RDA calculations assume adequate energy intake

Protein Supplementation

• In developing countries protein and energy supplements may improve pregnancy outcomes when women are undernourished

• There is little evidence that protein supplementation affects outcome in developed countries

Adverse Effects of Protein Supplementation

• Several human and animal studies of protein supplementation have found adverse effects including retarded fetal growth, increase in prematurity, and increased neonatal deaths.

Energy and protein intake in pregnancy – Cochrane, 2010

• To assess the effects of advice to increase or reduce energy or protein intake, or of actual energy or protein supplementation or restriction, during pregnancy on energy and protein intakes, gestational weight gain, and the outcome of pregnancy.

Dietary Advice:

• 5 trials (1135 women)

• Nutritional advice to increase energy and protein intake was successful in achieving those goals

• No consistent benefit was observed on pregnancy outcomes.

Balanced Energy/Protein Supplementation

• 13 trials (4665 women)

• Modest increases in maternal weight gain & mean birthweight

• Substantial reduction in SGA

• No effect on preterm birth

• Reduced risk of stillbirth and neonatal death

High-protein Supplementation

• 2 trials (529 women)• Small, non-significant increase in

maternal weight gain• Non-significant reduction in mean

birthweight• Significantly increased risk of SGA birth• Non-significantly increased risk of

neonatal death.

Isocaloric Protein Supplementation

• 3 trials, 966 women

• Increased risk of SGA

Energy/protein Restriction with Overweight or High Weight Gain

• Significantly reduced weekly maternal weight gain & mean birthweight

• No effect on pregnancy-induced hypertension or preeclampsia.

Author’s Conclusions

• High-protein/balanced-protein supplementation alone is not beneficial and may be harmful to the fetus.

• Protein/energy restriction of pregnant women who are overweight, or exhibit high weight gain, is unlikely to be beneficial and may be harmful to the fetus.

Lipids

• General lipid recommendations for pregnancy

• Essential fatty acids & LCPUFA

• Trans FA

Lipids: Maternal

• Metabolism changes to:– meet increased maternal needs for energy

and hormone precursors– to insure adequate fetal accretion

• Serum cholesterol rises 25-40%

• Triglycerides rise 200-400%

Lipids: Maternal Recommendations, 2002 DRI

• 30% of kcals from fat is a reasonable goal in pregnancy.– There is no need to try to affect the

physiological rise in blood lipids

Essential and LCPUFA

Important Fatty Acids

LNA -linolenic 18:3n-3

LA Linoleic 18:2n-6

EPA Eicosapentaenoic 20:5n-3

ARA Arachidonic 20:4n-6

DHA Docosahexanoic 22:6n-3

Background: LCPUFA

• Dietary sources of n-3 and n-6 fatty acids are essential.

• Fetal ability to elongate and desaturate fatty acids is limited.

• Conversion of LNA to DHA is highly variable among individual infants.

Innis. J Peds. 2003

Fetal Implications• Human brain is lipid based; ~ 60% of dry

weight• 30% of fetal CNS tissue is LCPUFA with n-3

to n-6 ratio of 2:1• Fetal brain development starts early &

experiences “growth spurt” during last trimester and 1st 6 months of life

• In 3rd trimester, storage of LCPUFA in fetal adipose tissue if adequate maternal sources

• Adequacy of LCPUFA associated with CNS and retinal function.

Arterburn et al, Am J Clin Nutr, 2006

Background: Placental Transfer

• The fetus is totally dependent on maternal intake and placental transfer.

• The placenta selectively transports LCPUFA

• Concentrations of DHA and ARA are 300 to 400 fold higher in fetal vs maternal plasma phospholipids

Innis. J Peds. 2003

Maternal LCPUFA status maters to the Infant

• Women with higher plasma ARA and DHA during pregnancy have infants with higher ARA and DHA

• Higher n-6 and n-3 status at birth results in higher ARA and DHA for several weeks.

Dunstan et al. Pediatr Res, 2007. Fish oil supplementation in pregnancy on breastmilk FA

composition over the course of lactation

• RCT, n=98, Fish oil (2.2.g DHA, 1.1 g EPA) vs olive oil from 20 wk to term

• Breastmilk had higher DHA & EPA at 3 d and 6 weeks

• Infants had higher DHA/EPA at 1 yr• Positive correlations between breastmilk

DHA/EPA and infant developmental scores

Maternal LCPUFA Status matters to the Pregnancy

• Eicosanoids derived from LCPUFA (prostaglandins, thromboxanes, prostacylcins, leukotrienes) play vital roles in pregnancy

• The ideal ratio of n-3 to n-6 remains unknown

• Dietary sources of EFA - both n-3 and n-6 are important

Hypertensive Disorders of Pregnancy and n-3 Fatty Acids

• Possible biological pathway: – Vasoconstriction and epithelial damage of

HDP is associated with imbalance of TXA2

(vasoconstrictor) and PGI2 (vasodilator)

• If increased dietary intake of n-3:– EPA competes with Arachadonic Acid for

enzymes so may have lower production of TXA2 and higher production of PGI3 (vasodilator)

HDP and n-3 Fatty Acids

• Epidemiological Studies:– several studies have found that women with HDP

have lower levels of n-3– lower incidence of HDP in fish eating populations

• RCT– “Compelling evidence for a beneficial effect of n-3

fatty acids on preeclampsia from recent prospective, double-blind studies is lacking (Jensen, Am J Clin Nutr, 2006)

Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-

eclampsia or intrauterine growth restriction,(Cochran Collaboration, 2006)

• Six trials, involving 2783 women• Results for pregnancies randomized to supplements:

– Mean gestation 2.6 days longer– Lower risk of birth <34 weeks (RR=0.69, 0.49-0.99)

– Birthweight slightly greater (47 g)– no overall differences between the groups in the proportion

of LBW or SGA babies – No clear difference RR of pre-eclampsia between the two

groups• Conclusion: “There is not enough evidence to support

the routine use of marine oil, or other prostaglandin precursor, supplements during pregnancy to reduce the risk of pre-eclampsia, preterm birth, low birthweight or small-for-gestational age.”

N-3 and Prolonged Gestation

• Faroe Islands: – high birthweights– longer gestations– diet high in marine oils

• Theory: n-3 interference with uterine prostaglandin production

N-3 and Prolonged Gestation

• Supplementation study: – increased gestational length by 4 days

– prolonged bleeding times & increased blood loss at delivery

N-3 intake and Depression by Country (Hibbeln, AJCN, 2006)

• In model with 20 countries, correlation between postpartum depression rates and energy from n-3 FA was r=-0.78, p<0.001)

N-3 intake and Depression by Country (Hibbeln, AJCN, 2006)

% of energy from dietary n-3 LCFA

Postpartum Depression (%)

Brazil 0.052 24

Germany 0.084 25

Ireland 0.090 14

USA 0.103 12

Sweden 0.139 9

Canada 0.146 13

Japan 0.374 2

Iceland 0.435 5

N-3 and Maternal Depression (Jensen, AJCN, 2006)

• “Recent observational trials and open-label trials of n-3 FA supplementation appears promising.”

• “At present, however, there is a paucity of data from controlled studies supporting the efficacy of n-3 FA in the prevention or treatment of depression during pregnancy or the postpartum period.”

Michael Crawford, Director, Institute for Brain Chemistry and Human

Nutrition, London• http://www.seafoodandhealth.org/index.

php?section=20&id=277“…the brain case of this little one-year-old fellow is nearly the same size as the mother’s. What that tells you is that the priority of human development is the brain; it’s not the body. Look at the size of the child’s hand compared to the mother’s. We know all about this, and I’m not going to dwell on it, but the priority is unquestionably, in homo sapiens, the brain. Physiological requirement is the brain, nutritional requirement priority is the brain, and the brain is made of lipids, so we’ve got to get these lipids to make our brains.’

Key Points of Crawford’s Presentation

• Humans evolved and thrived near waterwith access to DHA• EU report that cost of “brain disorders” has

overtaken all other costs of ill health and there are predictions that mental health will be in the top three burdens of ill health for the world by 2020

• We need to restore the food chain to give better balance of n-3 to n-6

• We need to invest in the ocean

Research Review, J Am Diet Assoc. 2009;109:1566-1575

• “Numerous studies, such as RCTs, cohort studies and ecological studies, have found a positive association between low n-3 levels and a higher incidence of maternal depression.”

Infant visual function/neural development (Jensen, 2006)

• Observational studies find both positive associations and no association.

• Small intervention studies: possible associations with attention & distractibility and visual functioning.

Essential Fatty Acids in Mothers and

Their Neonates (Hornstra, AJCN, 2000)

• Maternal essential fatty acid status declines during pregnancy (absolute plasma levels in-crease, but non-essential increase more).

• Pregnancy may cause maternal DHA depletion/mobilization from maternal stores. (Implications for close pregnancy spacing)

• Essential PUFA status of newborns is restricted by that of the mother and may not be optimal.

• Maternal PUFA supplementation affects neonatal PUFA status.

• Maternal linoleate intake during pregnancy is negatively related to neonatal head circumference.

• In preterm infants positive relationship between DHA in umbilical artery and birth weight. Length, and OFC.

Hornstra - Implications

• Humans evolved with limited ability to elongate and desaturate EFA?

• Limitations require special consideration during increased requirements of fetal development, lactation, and neonatal development.

2010 Review • Data derived from observational studies have found that

omega-3 fatty acid consumption during pregnancy either in the diet or via supplements is associated with improved neurodevelopmental outcomes in the child.

• At present, there is not enough data to recommend omega-3 fatty acid supplementation for the sole purpose of prolonging gestation or reducing the risk of preterm birth.

• Epidemiologic data have shown that low seafood intake during pregnancy correlates with higher levels of depressive symptoms during pregnancy. However, randomized, controlled trials have failed to demonstrate a clear benefit to omega-3 fatty acid supplementation during pregnancy and postpartum to prevent depressive symptoms.

Coletta, et cl. Omega-3 Fatty Acids and Pregnancy, Rev Obstet Gynecol. 2010 Fall; 3(4): 163–171.

2004 EPA and FDA Advice for:

• Women Who Might Become Pregnant

• Women Who are Pregnant

• Nursing Mothers

• Young Children

BALANCING CHOICES:SUPPORTING CONSUMER SEAFOODCONSUMPTION DECISIONS, IOM, 2006

BALANCING CHOICES:SUPPORTING CONSUMER SEAFOODCONSUMPTION DECISIONS, IOM, 2006

By following these three recommendations for selecting and eating fish or shellfish, women and young children will receive the benefits of eating fish and shellfish and be confident that they have

reduced their exposure to the harmful effects of mercury: • Do not eat Shark, Swordfish, King Mackerel, or Tilefish because

they contain high levels of mercury. • Eat up to 12 ounces (2 average meals) a week of a variety of

fish and shellfish that are lower in mercury. – Five of the most commonly eaten fish that are low in mercury are

shrimp, canned light tuna, salmon, pollock, and catfish. – Another commonly eaten fish, albacore ("white") tuna has more

mercury than canned light tuna. So, when choosing your two meals of fish and shellfish, you may eat up to 6 ounces (one average meal) of albacore tuna per week.

• Check local advisories about the safety of fish caught by family and friends in your local lakes, rivers, and coastal areas. If no advice is available, eat up to 6 ounces (one average meal) per week of fish you catch from local waters, but don't consume any other fish during that week

FDA Draft Report Urges Consumption of Fish, Despite Mercury Contamination (Washington Post 12/12/08 )

• “The report argued that nutrients in fish, including omega-3 fatty acids, selenium and other minerals could boost a child's IQ by three points.”

• “The greatest benefits, the FDA report said, would come from eating more than 12 ounces of fish a week, which is the current limit advised for pregnant women, women of childbearing age, nursing mothers and young children.”

• "This is an astonishing, irresponsible document," said Richard Wiles, the environmental group's executive director. "It's a commentary on how low FDA has sunk as an agency. It was once a fierce protector of America's health, and now it's nothing more than a patsy for polluters."

• “But Gavin Gibbons, a spokesman for the National Fisheries Institute, applauded the FDA's efforts. "This is a science-based approach," he said. "And you start to see a picture emerge that shows the clear benefits of eating seafood outweigh the risks of a trace amount of mercury in fish."

Washington State Fish Advisory for Mercury for

Women of Childbearing Age and Children Under Six • Do not eat any shark, swordfish, tilefish, king mackerel or

either fresh caught or frozen tuna steaks. • Limit the amount of canned tuna you eat, based on your

bodyweight. General guidelines are: – Women of childbearing age should limit the amount of

canned tuna they eat to about one can per week (six ounces).

– Children under six should eat less than one half a can of tuna (three ounces) per week. Specific weekly limits for children under six range from one ounce for a twenty pound child, to three ounces for a child weighing about sixty pounds.

– Choose chunk light tuna over albacore white to further reduce your exposure to mercury.

– Find out about fish advisories.

http://www.doh.wa.gov/fish/FishAdvMercury.htm

• For freshwater bass:– Woman of childbearing age and children under six

should limit their consumption of freshwater bass (largemouth and smallmouth) to no more than 2 meals/month.  Additional information can be obtained from the "Statewide Bass Advisory"  report and the "Freshwater Largemouth and Smallmouth Bass Consumption Advisory Due to Mercury Contamination" fact sheet

• Health problems caused by mercury are:– Babies whose mothers ate fish contaminated with

mercury during pregnancy, are at greater risk for changes to their nervous systems.  These changes can affect their ability to learn.

Health problems, cont.

• In adults, several neurological signs and symptoms are among the common features of chronic high-dose exposures to methylmercury in adults. These can include peripheral neuropathy (tingling in the hands and feet), tremor, problems walking, dizziness, visual and hearing difficulties, and memory impairment (NRC 2000, ATSDR 1999). These symptoms are generally not associated with the level of exposure to methylmercury through the consumption of fish in the U.S. Mercury has been shown to accumulate in the heart. Recent findings investigating chronic low-dose exposures have been associated with changes in blood-pressure and abnormal heart function (Salonen et al. 1995, Sorensen et al 1999) as well as increased risk of heart-attack (Guallar et al. 2002).

What about other contaminants?

• Mercury in fish is a big concern, but fish might also contain other contaminants. Some kinds of pesticides and chemicals called "PCBs" also get into fish. PCBs and pesticides are mostly found in the skin and fatty part of fish, so if you cut and cook fish in ways that remove the skin and fat, you can lower the amount of pesticides and PCBs in your food.

Recent Recommendations for Fish Intake in Pregnancy

• Consumer Reports, July 2006: – “Given the uncertainties about the safety of even

chunk-light tuna, we think it’s prudent for pregnant women to avoid canned tuna entirely.”

– Women of childbearing age who aren’t pregnant: “Mercury can linger in the body after you stop eating fish, so we advise these women to eat no more than about 3 chunk-light cans per week or one can of solid-light or white tuna.”

Hibbeln et al. Maternal seafood consumption in pregnancy & neurodevelopmental outcomes in childhood. Lancet 2007

• Maternal seafood consumption of less than 340 g per week in pregnancy did not protect children from adverse outcomes; rather, we recorded beneficial effects on child development with maternal seafood intakes of more than 340 g per week, suggesting that advice to limit seafood consumption could actually be detrimental. These results show that risks from the loss of nutrients were greater than the risks of harm from exposure to trace contaminants in 340 g seafood eaten weekly.

Docosahexaenoic acid supplementation in pregnancy and lactation

(Carlson, AM J Clin Nutr, 2009)

• large differences in maternal DHA status within and among cultures– US pregnant and lactating women are among the

lowest consumers of DHA in the developed world– US Black women average 68 mg/d of DHA (far below

recommended levels)

• may result in functional differences in development with critical windows– modest decreases in brain DHA cause effects on

dopaminergic and serotonergic systems that are not reversible after weaning in the rat

Carlson, cont.

• The variability in RBC arachidonic acid and DHA suggest variable:– maternal biosynthesis– maternal to fetal transfer– status of nutrients required for DHA

synthesis– genetic differences in the ability to

synthesize DHA

To Supplement?, Carlson, 2009

– “There is considerable (although not universal) support from experimental studies for the idea that DHA is a conditionally essential nutrient for the developing infant”

– “Experimental studies of the quality and quantity needed to show that DHA supplementation is important for either infant or child or mother are still few and more work is needed.”

Effect of DHA Supplementation During Pregnancy on Maternal Depression and Neurodevelopment of Young

Children, JAMA, 2010. Makrides et al. • RCT; 2399 women • Docosahexaenoic acid–rich fish oil capsules

(providing 800 mg/d of DHA) or matched vegetable oil capsules without DHA from study entry to birth

• “The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood.”

Possible Adverse Effects

• Animal models: Excess omega-3 fatty acid consumption by mothers during pregnancy and lactation caused shorter life span and abnormal Auditory Brainstem Responses in old adult offspring.(Church, 2010)

Essential Fatty Acids Requirements in Pregnancy

• FAO recommends 4.5% of daily energy as EFA (essential fatty acids) in pregnancy and 6% in lactation– If kcals are inadequate energy based

recommendations may be misleading

2002 DRI for n-6 Fatty Acids in Pregnancy

• AI = 13 g/day linoleic acid

• Based on median linoleic acid intake of pregnant women in US where deficiency is “basically non-existent.”

• AI for non-pregnant women = 12 g/day

2002 DRI for N-3 Fatty Acids in Pregnancy

• Demand driven by:– fetus– placental tissue– secretion during lactation

• AI = 1.3 g/day of -linolenic acid – Based on median -linolenic acid intake of

pregnant women in US where deficiency is “basically non-existent.”

– non-pregnant AI=1.1 g/day -linolenic acid

– DHA and EPA can contribute toward total n-3

Trans Fatty Acids

• Side product of catalytic hydrogenation of vegetable oils and biohydrogenation in the rumen of animals

• Animal studies show discrimination against transport of trans FA across the placenta, but some are transported.

• Trans FA inhibit elongation of EFA• Trans FA in plasma of human preterm

infants was found to be inversely associated with LCPUFA

Emerging Issues

• trans unsaturated fats may increase the risk of ovulatory infertility (Chavarro, AJCN, 2007)

• birth length (BL) and head circumference (HC) were significantly and negatively related to the C18:1trans concentration in phospholipids isolated from umbilical plasma (HC), umbilical arterial walls (HC and BL), or umbilical venous walls (BL). (Hornstra, Atherosclerosis Supplements, 2006)

Trans Fatty Acids

• Infant formula has few trans FA, breastmilk content reflects maternal diet.

• What to recommend?

Trans Fatty Acid & Policy

“These considerations support strategies to effectively remove TFA from industrial sources from the diet of pregnant and lactating women, and young children, while improving dietary intakes of the n − 3 fatty acids. .”

Innis, Atherosclerosis Supplements, 2006

Macronutrient Status

• Important throughout the reproductive years:– Periconceptual period– Pregnancy– Lactation– Inter-pregnancy interval