The Role of Omega 3 s in Pregnancy Robert Gibson, Director FOODplus Research Centre Adelaide, Australia Do pregnant and lactating women need omega 3s? And how much? Omega 3 s in Pregnancy systematic reviews Effect of pregnancy fish oil supplementation: Mean duration of gestation was increased by 2.5 days No prevention of preterm birth <37 weeks GA, significantly reduced the risk of early preterm birth (<34 weeks GA) No consistent benefit during pregnancy and/or lactation on child neurodevelopment visual acuity Child Nutrition Research Centre Women s & Children s Health Research Institute; Children s, Youth and Women s Health Service; Flinders Medical Centre; University of Adelaide to Optimize Mother Infant Outcome Designed to assess postnatal depression in women and neurodevelopmental outcome in early childhood Largest trial of n-3 LCPUFA supplementation with 2399 women Australian women consume low (~1mg/d) included more women than systematic review Also assessed pregnancy outcomes Makrides, Gibson, McPhee et al, JAMA 21;34:1675-83 Study Design Randomized controlled trial Women with singleton pregnancy at <2 weeks gestation, general population group 3x5mg capsules of -rich fish oil concentrate providing 8mg of /day group 3x5mg capsules containing a blend of 3 vegetable oils (to match Australian diet) with no Intervene from study entry to birth 1
and pregnancy outcome Gestation Duration (8mg, 1mg EPA) (n=1197) (n=122) Duration of gestation, d 282 281 p=.5 Birth <37 weeks 5.6% 7.3% p=.9 Birth <34 weeks 1.1% 2.3% p=.3 Post-term induction/ post-term pre-labour C- section 18% 14% p<.1 Makrides, Gibson, McPhee et al, JAMA 21;34:1675-83 Birth anthropometrics (n=1197) (n=122) Adjusted effect (95% CI) Birth weight (g) 3475 347 68 (23, 114) Birth weight <25g (%) Birth weight >4g (%) 3.4 5.3.65 (.44,.96) 16.3 12.8 1.27 (1.5, 1.55) Birth weight z-score.28.22 NS SGA for weight (%) 6.1 6.8 NS LGA for weight (%) 17.1 14.4 1.19 (.99, 1.43) Makrides, Gibson, McPhee et al, JAMA 21;34:1675-83 Zhou et al, AJCN 212;95:1378-1384 neonatal outcomes Neonatal hypoglcaemia 7/1197, 5.8% 58/122, 4.9% Oxygen for CLD 2/1184,.17% 4/1179,.34% Neonatal convulsion /1184 5/1177,.42%* Admission to NICU 21/1197, 1.8% 37/122, 3.1%* Brain injury /1184 5/1176,.43%* NEC 1/1184,.8% /1177 Sepsis 3/1184,.25% 2/1177,.17% Perinatal death (stillbirth or death in the first 28 days) *p<.5 3/1197,.25% 12/122, 1.%* Zhou et al, AJCN 212;95:1378-1384 Gestational Diabetes (GDM) and Pre-Eclampsia (PE) GDM based on GTT GDM clinical diagnosis PE based on PIH and proteinuria PE clinical diagnosis (n=1197) PIH=pregnancy induced hypertension (n=122) Adjusted effect (95% CI) 5.8% 5.6% 1.4 (.75, 1.44) 8.1% 8.3%.97 (.74, 1.27) 5.% 4.9% 1.3 (.72, 1.48) 4.3% 4.9%.87 (.6, 1.25) Zhou et al, AJCN 212;95:1378-1384 Kansas Outcomes Study (KUDOS), Carlson et al, 213 Placebo N=154 N=147 P-value GA (d) 272.7 275.6.41 Preterm birth (<37 wks) 8.8% 7.8% NS Early preterm birth (<34 wks) 4.8%.6% P=.25 NICU admission 8.8% 8.4% NS Days in NICU (mean #) 38.4 7.8 P=.34 Randomized to 6 mg /d or placebo at a mean of 14 wks gestation Carlson et al, AJCN 97;88-15 213 2
Updated Systematic Review Variable Cochrane review 26 Updated Cochrane review (unpublished) Mean Difference in Gestation Length (d) 2.5 (95% CI 1. to 4.1) 1621 women, 3 trials 2. (95% CI 1.1 to 3.) 4289 women, 5 trials What about the brain? Does play a role in: - Post natal depression? - Cognitive development in infancy? Relative Risk of Preterm Birth (<37 w) Relative Risk of Early Preterm Birth (< 34 w).92 (95% CI.79 to 1.7) 1916 women, 5 trials.69 (95% CI.49 to.99) 86 women, 2 trials.92 (95% CI.8 to 1.4) 5586 women, 8 trials.6 (95% CI.44 to.81) 356 women, 4 trials No effect in Mexico study (4mg ) and Risk of postnatal depression Variable All women EPDS>12, % 6 wk 6 mo New medical diagnosis during study, % Subgroup, hi-risk women EPDS>12, % 6 wk 6 mo n=1197 9.67 9.61 9.74 n=122 11.19 1.88 11.5 Adj. RR (95% CI).85 (.7,1.2).87 (.68,1.1).83 (.66,1.5) 3.39 4.12.8 (.62,1.2) N=298 2.9 21.2 2.8 N=287 24.2 22.1 26.2.87 (.68,1.12).96 (.71, 1.3).81 (.6, 1.8) Summary There is consistent evidence that n-3 LCPUFA given in the 2 nd half of pregnancy will extend the mean gestation The dose > 6mg/d for women consuming Western diets While there is no evidence that n-3 LCPUFA, in the range of levels tested, causes direct harm, the fact that normal gestation is extended could be a problem Note: Effect size much smaller than suggested by cohort studies What about the infant? 3
and Development in and to Improve Neurodevelopmental Outcome 657 infants born <33 weeks gestation >95% follow-up Test dose: 9mg/day largely to lactating women Intervention to 4 w PMA JAMA 29;31:175-82 to Optimise Mother Infant Outcome 2399 pregnant women from 2 weeks gestation >95% follow-up Test dose: 8mg/day to pregnant women Intervention to delivery JAMA 21;34:1675-83 Cognitive (and Motor) Development assessed using the Bayley Scales of Infant Development at 18 months Provide standardized developmental quotient (DQ) scores Mean DQ from Bayley mental/cognitive scales 11 Preterm 11 Term Percentage with DQ < 85 (mild cognitive delay) 4 Preterm 4 Term 1 9 std- hi- 1 9 3 2 1 P=.5 std- hi- 3 2 1 P=.1 8 8 Percentage with DQ < 7 (major cognitive delay) 15 12 Preterm Term Who are the susceptible children? Preterm infants with the lowest gestational age or lowest birth weight 9 6 P=.2 std- hi- The sickest infants 3 4
Bayley mental DQ by birth weight strata Percentage of Infants <125g with Mild and Significant Mental Delay 1 P=.3 P=.67 4 P=.1 95 3 9 hi- std- 2 P=.16 hi- std- 85 131 141 166 175 1 21 46 9 18 8 <125g >=125g MDI <85 MDI <7 Makrides, Gibson, et al, JAMA 29;31:175-82 Makrides, Gibson, et al, JAMA 29;31:175-82 Summary: the tail of preterm infants Significant interaction effect by the pre-specified randomisation strata (birth weight <125g or 125g) Differences between the groups were evident in infants born <125g but not those born weighing 125g Consistent with hypothesis that infants born at earliest gestations are the most vulnerable to insufficiency Growth : No Effect of on Growth At 3 and % years -1531 children (92.2%) No difference in: BMI z-score and % body fat mass overweight or obese Body weight height z-scores waist and hip circumferences Total and % lean mass Respiratory 5
: Percentage of infants requiring oxygen at 36 weeks 5 Allergy 4 P=.4 3 2 P=.7 hi- std- 1 All <125g >125g Manley B et al. Pediatrics 211;128;e71 : Allergy at 1 year 76 families with high hereditary risk Assessed for IgE mediated allergies at 1 year Palmer et al, BMJ, 212;344:e184 Summary There is consistent evidence that n-3 LCPUFA given in the last trimester either in utero or ex utero results in a range of clinical benefits to the child Dose for preterm infants ~ 6mg/kg/d Dose for term infants not clear There is no evidence that n-3 LCPUFA, in the range of levels tested, causes harm The effect had disappeared by age 3 The CNRC/FoodPlus Team 6