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Int\tJ\tEndocrinol\n\t2011:269853,\t2011;\tWu\tG\tet\tal:\n\tBiological\tmechanisms\tfor\tnutritional\tregulation\tof\nmaternal\thealth\tand\tfetal\tdevelopment,\t\nPaediatr\tPerinat\tEpidemiol\n\t26:4,\t2012a.\nIn\taddition\tto\tfetal\tgrowth\trestriction,\tany\tadverse\tmaternal\tcondition,\tincluding\tpoor\tnutritional
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(\nBloomfield,\t2011\n).\tIn\tthe\tUnited\tStates\trates\tare\thighest\tamong\tnon-Hispanic\tblack\twomen,\tand\tit\nis\tunclear\tif\tearly\tfetal\tdevelopmental\tprogramming\tis\tplaying\ta\trole.\tPreterm\tdelivery\trates\tare\nhigher\twith\tART,\tamong\tboth\tsingletons\tand\tmultiples,\tpossibly\texplained\n\tin\tpart\tby\tthe\tunderlying\nmedical\tconditions\tthat\talso\tincrease\tinfertility\t(
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medical\tconditions\tthat\talso\tincrease\tinfertility\t(\nACOG,\t2016a\n).\nAlthough\tobesity\tdoes\tnot\tpredict\toptimal\tnutrition,\tit\tis\tsomewhat\tprotective\tfor\tpreterm\tdelivery.\nHowever,\tprepregnant\tunderweight,\tcombined\twith\tlow\tweight\tgain\tduring\tpregnancy,\thas\tan\nadditive\teffect\ton\tpreterm\tdelivery\tand\tLBW\trisk.\tEven\tfor\tthose\twomen\tof\tnormal\tweight,\tlow
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weight\tgain\tdoubles\tthe\n\trisk\tof\tpreterm\tdelivery,\twhile\tweight\tloss\ttriples\tthe\trisk\t(\nBloomfield,\n2011\n).\tShort\tinterconceptual\tperiods\tare\tassociated\twith\tincreased\trates\tof\tpreterm\tbirths.\tIn\ta\nrecent\tstudy,\tthose\twomen\twho\twere\tunderweight,\twith\tan\tinterconceptual\tperiod\tof\tless\tthan\t6
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months,\tand\twho\thad\tinadequate\tweight\tgain\thad\tan\tincreased\trisk\tof\tnearly\t3.5\ttimes,\tresulting\tin\nover\t25%\trate\tof\tpreterm\tdelivery\n\t(\nLengyel\tet\tal,\t2017\n).\nOxidative\tstress,\tmetabolic\tstress,\tand\tinflammation\tmay\tall\tbe\timportant\tfactors\tin\tincreasing\trisk
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0.0598168782889843, 0.07974286377429962, -5.455694918055087e-8, 0.003352103754878044, -0.004504169803112745, 0.00900870282202959, -0.014599545858800411, 0.05831718072295189, -0.041967447847127914, 0.09346004575490952, 0.06028015911579132, 0.012338364496827126, 0.0131705766543746, 0.023157939314842224, 0.11652863025665283, -0.0472940094769001, 0.00977894477546215, 0.06269924342632294, 0.02038019895553589, 0.02240106649696827, 0.06855050474405289, -0.015442142263054848, -0.08009763807058334, 0.01092553324997425, 0.05383019894361496, -0.07204172015190125, -0.03869307041168213, -0.03248116746544838, 0.050258755683898926, -0.029072370380163193, -0.010805623605847359, -0.008897746913135052, 0.01092498004436493, 0.10774600505828857, -0.02327554300427437, -0.015515472739934921, -0.038919053971767426, -0.02428383193910122, 0.03170933574438095, -0.03686940670013428, -0.042742032557725906, 0.020747894421219826, 0.11675278097391129, 0.01663403958082199, 0.020304378122091293, 0.01699010841548443, 0.08940146118402481, 0.02119031921029091, -0.08128038048744202, -0.024634450674057007, 0.10142914205789566, -0.026511026546359062, -0.044926367700099945, -0.029717635363340378, 0.10611408203840256, 0.0049368771724402905, -0.06004510074853897, 0.000994655885733664, 0.0068686832673847675, 0.09919091314077377, 0.0427626371383667, -0.021925516426563263, 0.02379540354013443, 0.10141851007938385, 0.06032320857048035, 0.06716109067201614, -0.04756821319460869 ]
but\tthere\tare\tno\npreconceptual\tstudies.\tSupplementation\twith\tLCPUFAs,\tprotein,\tand\tvitamins\tE\tand\tC\tare\tnot\neffective\t(\nACOG,\t2012\n).\tAlthough\tno\tideal\tdiet\thas\tbeen\tidentified,\tone\tcontaining\tfruits,\tvegetables,\nwhole\tgrains,\tand\tfish\thas\tbeen\tobserved\tto\tbe\tassociated\twith\tlower\trisk\tof\tpreterm\tdelivery.\nProbiotics\tmight\tbe\thelpful\t(
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-0.012276053428649902, 0.06333472579717636, -0.03855930641293526, 0.08052366971969604, 0.06961844116449356, -0.062218233942985535, -0.015740953385829926, 0.0427747406065464, -0.018484588712453842, -0.04684807360172272, 0.019074762240052223, 0.11550632119178772, -0.008355027064681053, -0.04599383473396301, -0.0023969165049493313, 0.02150443196296692, 0.044224634766578674, 0.04065529629588127, -0.05494432896375656, 0.06132083386182785, 0.05050622671842575, 0.0458548404276371, 0.09262191504240036, -0.0399189330637455 ]
Probiotics\tmight\tbe\thelpful\t(\nEnglund-Ögge\tet\tal,\t2014\n)\tand\tsmoking\tcessation\tis\thelpful\t(\nACOG,\n2012\n).\tParticular\ttoxins\tmay\tincrease\tthe\trisk\tof\tprematurity.\tOne\tstudy\tfound\tnearly\tdouble\tthe\trisk\nof\tpreterm\tdelivery\tif\twomen\tconsumed\tmore\tthan\tfour\tservings\tof\tdiet\tsoda\tper\tday\t(\nBloomfield,\n2011\n),\talthough\tthat\tfinding\thas\tbeen\tdisputed\t(
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Bloomfield,\n2011\n),\talthough\tthat\tfinding\thas\tbeen\tdisputed\t(\nLa\tVecchia,\t2013\n).\tLicorice\t(\nGlycyrrhiza\tglabra\n\troot)\nblocks\tthe\tenzyme\tthat\tinactivates\tcortisol,\tand\tthe\teffect\ton\tpreterm\tdelivery\trisk\tis\tdose-related.\nSimilar\tresults\tare\tseen\twhen\tthe\tmother\tis\texposed\tto\tpsychological\tstress\t(see\t\nClinical\tInsight:\nStress\tduring\tPregnancy
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Clinical\tInsight:\nStress\tduring\tPregnancy\n).\tThe\trole\tof\tpaternal\tnutrition\tin\tpreterm\tdelivery\trisk\tis\tunexplored\n(\nBloomfield,\t2011\n).\nThe\teffect\tof\tpoor\tmaternal\tnutrition\tor\texposure\tto\ttoxins\tmay\tfollow\tthe\tinfant\tfor\tdecades.\tA\nvery\tpreterm,\tgrowth-restricted\tbaby\tmay\tsuffer\tpermanent\tbrain\tdamage.\t\nNeural\ttube\tdefects\n(NTDs)
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Neural\ttube\tdefects\n(NTDs)\n\tmay\tcause\tlifelong\tproblems\twith\tmobility\tand\tbodily\tfunctions.\tFetal\talcohol\tsyndrome\n(FAS)\tis\ta\tmajor\tcause\tof\tintellectual\tdevelopmental\tdisability.\tHowever,\teven\tthose\tbabies\twho\tare\nborn\twith\tno\tapparent\tdefects\tmay\tsuffer\tincreased\trisk\tof\tchronic\tdiseases\tbecause\tof\ta\tless-than-\noptimal\tprenatal\tenvironment.\tSee
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optimal\tprenatal\tenvironment.\tSee\t\nFig.\t14.3\n\tfor\ta\tsummary\tof\tthe\teffects\tof\tmaternal\tmalnutrition.
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FIG.\t14.3\nMajor\tnegative\teffects\tof\tmaternal\tmalnutrition\t(both\tunder-\tand\tovernutrition)\ton\tmother\tand\tinfant.\nEpigenetic\teffects\nCompromises\tin\tstructural\tor\tcognitive\tpotential\tmay\tnot\tbe\tevident\twhen\tan\tinfant\tis\tborn\tbut\tmay\nmanifest\tlater\tin\tlife.\tA\tchild\twith\tIUGR,\toften\tresulting\tfrom\tmaternal\thypertension\tor\tsevere
[ 0.006784065626561642, -0.023742755874991417, 0.08248810470104218, 0.01519093755632639, -0.06759414821863174, 0.04422933980822563, 0.08920518308877945, -0.027089638635516167, -0.004292619880288839, 0.08380363136529922, 0.12348474562168121, -0.08355791866779327, 0.0315997339785099, 0.030813738703727722, 0.02992972917854786, 0.02859235554933548, -0.032795120030641556, 0.03099009580910206, -0.0576467365026474, -0.04239250347018242, 0.002640356309711933, 0.05045023933053017, 0.04753057658672333, -0.016837071627378464, 0.018329547718167305, 0.0006052718381397426, -0.05497926101088524, -0.037748388946056366, 0.03771228715777397, -0.07505703717470169, -0.10519241541624069, 0.08003342151641846, -0.06754036247730255, 0.00757464487105608, 0.015886424109339714, 0.02277703583240509, -0.06266073137521744, -0.005554012954235077, 0.07605715841054916, 0.04087772220373154, -0.01750536449253559, -0.06757216900587082, -0.053239066153764725, 0.007685868535190821, 0.03999697044491768, 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0.026109758764505386, -0.0469813346862793, 0.01084475964307785, -0.01390227023512125, -0.0043973857536911964, -0.014310944825410843, 0.007468904368579388, 0.038055144250392914, 0.00930226780474186, 0.06743275374174118, 0.008818583562970161, -0.009564789943397045, -0.10448296368122101, -0.042759113013744354, -0.00939198024570942, 0.033587340265512466, 0.11872544139623642, -0.07248373329639435, 0.018353290855884552, -0.08176175504922867, 0.030062122270464897, -0.16108983755111694, 0.05426608398556709, 0.0008373938617296517, 0.07106884568929672, 0.009899403899908066, -0.0009985408978536725, 0.03212299942970276, 0.06013351306319237, 0.055273622274398804, -0.05426656827330589, -0.03916751220822334, 0.046566564589738846, 0.030270859599113464, 0.0018741352250799537, 0.038407281041145325, -0.025940818712115288, -0.12019214034080505, -0.0012284539407119155, 0.006741466000676155, -0.0221095010638237, 0.0914653092622757, 0.009854121133685112, 0.036023013293743134, -0.02691127546131611, 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0.03701849281787872, -0.018965402618050575, 0.06597135215997696, 0.10725405067205429, -4.57819027133155e-8, 0.01752859726548195, -0.02375103160738945, -0.010102382861077785, 0.00028283425490371883, 0.025472942739725113, -0.00809682160615921, 0.06484448909759521, 0.02998095192015171, -0.038238879293203354, -0.004583039321005344, 0.024224501103162766, 0.12584729492664337, -0.047260016202926636, -0.042699724435806274, 0.08082057535648346, 0.02135232277214527, -0.0030397078953683376, 0.07850705087184906, -0.015222616493701935, -0.03238051384687424, -0.0039004485588520765, 0.0737052634358406, -0.016628306359052658, -0.005181219428777695, -0.0625530555844307, 0.0009722562390379608, -0.02004544623196125, 0.018360428512096405, 0.04428499564528465, 0.017742983996868134, 0.07950370758771896, -0.028708869591355324, -0.040182847529649734, -0.044559016823768616, -0.06656727194786072, 0.02261035330593586, -0.0391361229121685, 0.0016890907427296042, 0.006152476649731398, 0.1335439682006836, 0.02039163187146187, 0.0035193355288356543, -0.006634807214140892, 0.08648840337991714, 0.016105175018310547, -0.0700811818242073, -0.025141824036836624, 0.05097998306155205, -0.017529847100377083, -0.02930518053472042, -0.014855287969112396, 0.10857252031564713, -0.002139212330803275, -0.011241544969379902, -0.06698787212371826, 0.024425702169537544, 0.07581055909395218, 0.07155745476484299, -0.03188123181462288, -0.0004912271979264915, 0.05886220932006836, 0.03540802747011185, 0.04526617005467415, -0.042152177542448044 ]
malnutrition\tor\tanemia,\tmay\thave\tpermanent\tmild\tneurodevelopmental\n\tcognitive\tabnormalities.\nBabies\tborn\tpreterm\tor\tgrowth\trestricted\tare\tmore\tlikely\tto\thave\ta\thigher\trisk\tof\tobesity,\ttype\t2\ndiabetes,\thypertension,\tand\tcardiovascular\tdisease\t(CVD)\tlater\tin\tlife\t(\nSimeoni\tet\tal,\t2018\n).\tThose
[ -0.002438295166939497, 0.003126752795651555, 0.03351915255188942, 0.02675248123705387, -0.07207261025905609, 0.018407199531793594, 0.07710188627243042, 0.03849850967526436, -0.09318262338638306, 0.04649965465068817, 0.08070738613605499, -0.04907120764255524, -0.011664018034934998, -0.015148131176829338, -0.04952011629939079, -0.04934673383831978, -0.014109151437878609, 0.02922007627785206, -0.04141082614660263, 0.004380693193525076, 0.005393370520323515, 0.1081223413348198, 0.03956741839647293, -0.0055012828670442104, 0.007507597096264362, -0.10895276069641113, -0.009844936430454254, -0.018087904900312424, -0.019672080874443054, -0.043553587049245834, -0.140745148062706, 0.04083238169550896, 0.010568018071353436, 0.015507925301790237, 0.001525007770396769, -0.012688599526882172, -0.0033525358885526657, -0.023313192650675774, -0.03417225927114487, 0.04564253240823746, 0.008761344477534294, -0.10933880507946014, -0.06752990931272507, 0.017760466784238815, 0.03439844772219658, 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Simeoni\tet\tal,\t2018\n).\tThose\nbabies\texposed\tto\tthe\tDutch\tfamine\tearly\tin\tgestation\twere\tat\thighest\trisk\tof\tCVD\tand\thad\tdouble\nthe\trisk\tfor\tschizophrenia,\tas\twell\tas\tan\tincreased\trisk\tof\tstress\tsensitivity\n\tand\tbreast\tcancer.\tThose\nexposed\tmidpregnancy\twere\tthree\ttimes\tmore\tlikely\tto\tdevelop\tmicroalbuminuria\tand\tdecreased
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creatinine\tclearance,\tas\twell\tas\thaving\tan\tincreased\trisk\tfor\tobstructive\tairway\tdisease;\tgrowth\nrestriction\twas\tcommon\tamong\tthose\taffected\tin\tthe\tlater\ttrimesters\t(\nRoseboom\tet\tal,\t2011\n;\nMatusiak\tet\tal,\t2014\n).\nGirls\tborn\tpreterm\tare\tmore\tlikely\tto\tdeliver\tpreterm\twith\ttheir\town\n\tpregnancies\tand\tmore\tlikely\nto\tdevelop\tanorexia\tnervosa\t(
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pregnancies\tand\tmore\tlikely\nto\tdevelop\tanorexia\tnervosa\t(\nBloomfield,\t2011\n).\tImmune\tfunction,\tlearning\tability,\tmental\thealth,\ncancer,\tand\taging\tare\tlikely\taffected\tby\tLBW.\tFunctional\tneural\tpathways\tcontrolling\tappetite\tand\nsatiety\tlikely\tdevelop\tin\tthe\tthird\ttrimester,\tso\tpreterm\tinfants\tmay\texperience\tdisruptions\tin\ttheir\ndevelopment.
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0.1006481945514679, -0.011352651752531528, -0.014845643192529678, 0.026215871796011925, 0.07158932834863663, 0.057730842381715775, -0.11144167929887772, -0.011607613414525986, 0.06545551866292953, 0.00792537909001112, -0.048059556633234024, -0.04248138144612312, 0.07166633009910583, 0.015917589887976646, -0.032339099794626236, -0.026194259524345398, 0.07334765791893005, 0.11108902841806412, 0.03904195874929428, -0.01815144717693329, 0.0379093736410141, 0.08399692177772522, 0.0883626714348793, 0.08469236642122269, -0.0149260014295578 ]
development.\nThose\tbabies\tborn\t\nlarge\tfor\tgestational\tage\t(LGA)\n\tor\texposed\n\tto\tmaternal\thyperglycemia\tor\nmaternal\tobesity\tare\tat\tincreased\trisk\tof\tchronic\tdiseases,\tlikely\tthrough\tmultiple\tmechanisms\t(see\nFocus\tOn:\n\tSpecial\tCase\tof\tObesity\n).\nBirth\tweight\tmay\tnot\tbe\tthe\tonly\tpredictor\tfor\tthe\tpropensity\tfor\tadult\tdisease.\tExposure\tto\thigh
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folate\tduring\tpregnancy\tis\tassociated\twith\tinsulin\tresistance\tand\tobesity\tin\tlater\tlife\tif\tcombined\nwith\tlow\tvitamin\tB\n12\n\tlevels,\tand\n\tincreased\trates\tof\tcancer\tare\tassociated\twith\tsupraphysiologic\nintakes\tof\tmethyl\tdonors\t(\nMilagro\tet\tal,\t2013\n;\tsee\t\nChapter\t6\n).\tMaternal\tand\tpaternal\tnutritional
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;\tsee\t\nChapter\t6\n).\tMaternal\tand\tpaternal\tnutritional\nimbalances\tare\tlikely\tto\tincrease\tthe\trisk\tof\tmetabolic\tsyndrome\t(\nDelCurto\tet\tal,\t2013\n).\nExposure\tto\tendocrine-disrupting\tchemicals\t(substances\tfound\tin\tthe\tenvironment\tthat\tinterfere\nwith\tthe\tsynthesis,\tmetabolism,\tor\taction\tof\tthe\tbody’s\n\thormones)\tmay\tmodify\tgene\texpression\tand
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hormones)\tmay\tmodify\tgene\texpression\tand\nthe\teffects,\tincluding\tincreased\trisk\tof\tobesity,\tinsulin\tresistance,\tand\ttype\t2\tdiabetes,\tmay\tbe\nnonlinear\t(i.e.,\tlow\tdoses\tmay\tbe\tmore\tharmful\tthan\thigh\tdoses)\t(\nBarouki\tet\tal,\t2012\n).\tIn\tone\tstudy,\nmothers\twho\tate\tan\tunbalanced\thigh-protein\tdiet\t(1\tpound\tred\tmeat/day,\tno\tcarbohydrate)\tduring
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late\tpregnancy\tproduced\toffspring\twho\texperienced\thigher\tcortisol\n\tlevels\twhen\texposed\tto\tstress\tas\nadults\t(\nBloomfield,\t2011\n).\nThis\tdevelopmental\tplasticity\tcan\tbe\thelpful.\tHowever,\twhen\tthere\tis\ta\tmismatch\tbetween\tin\tutero\nprogramming\tand\tthe\tlater\tenvironment,\tthe\trisk\tof\tchronic\tdisease\trises.\tA\tfetus\tmay\tdevelop\ta
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“thrifty\tphenotype,”\tadapting\tto\tpoor\tnutritional\tconditions\tby\tbeing\tmore\tefficient\tin\tacquiring\tand\nconserving\tenergy.\tHowever,\twhen\tlater\texposed\n\tto\tan\tenvironment\twith\thigher\tavailability,\tthis\n“thrifty”\tadaptation\tmay\tpredispose\tthe\toffspring\tto\tthe\tdiseases\tof\taffluence,\tincluding\tobesity\tand
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type\t2\tdiabetes.\tIn\taddition,\tharm\tmay\talso\tbe\tcaused\tby\tovercompensation\tlater\twith\texcessive\ncatch-up\tgrowth.\tAltered\torgan\tstructure,\tcell\tnumbers,\tand\tmetabolic\tfunctioning,\tincluding\npremature\taging\tof\ttissues,\tall\tappear\timportant\t(\nBurton\tet\tal,\t2016\n).\nExposure\tof\tthe\tembryo\tor\tfetus\tto\tspecific\tmaternal\tnutrients,\tas\twell\tas\tenvironmental
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contaminants,\tcan\tturn\tthe\timprinting\tgenes\tthat\tcontrol\tgrowth\tand\tdevelopment\ton\tor\toff,\tbut\tthe\namounts,\ttiming,\tand\teffects\tare\tstill\tbeing\tinvestigated.\tPaternal\tnutrient\timbalance\tand\tgene-\nenvironment\tinteractions\tare\talso\tlikely\timportant\t(\nBarouki\tet\tal,\t2012\n;\t\nDelCurto\tet\tal,\t2013\n).\nAlthough\tthe
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Barouki\tet\tal,\t2012\n;\t\nDelCurto\tet\tal,\t2013\n).\nAlthough\tthe\n\tconcept\tof\tthe\tDOHaD\toriginally\tfocused\ton\tundernutrition,\tovernutrition\talso\tis\tbeing\nstudied.\tEffects\tof\tmacro-\tand\tmicronutrients,\tas\twell\tas\tphytonutrients\tand\thypoxia,\tare\tbeing\nexamined,\tprimarily\tthrough\tanimal\tstudies\tso\tfar,\tand\tthe\tideal\tmaternal\tand\tpaternal\tdiet\tfor
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epigenetic\teffects\thas\tnot\tyet\tbeen\testablished\t(\nVanhees\tet\tal,\t2014\n).\tIt\tappears\tthat\tthe\tepigenetic\neffect\tof\tpreconceptual\n\tobesity\tis\tstronger\tfor\tmaternal\tthan\tpaternal\tobesity\t(\nGodfrey\tet\tal,\t2017b\n).\nHowever,\tthe\tpaternal\tdiet\tbefore\tconception\tdoes\tappear\tto\taffect\tthe\toffspring\tepigenetically\tand
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-0.021799810230731964, 0.10825852304697037, 0.08030738681554794, -4.5127155345880965e-8, 0.013853090815246105, -0.0433838851749897, 0.013933265581727028, -0.024915603920817375, 0.054319582879543304, 0.01255281176418066, -0.011474314145743847, 0.018184898421168327, 0.022549014538526535, -0.07469874620437622, 0.01532762497663498, 0.05791404843330383, -0.0761457309126854, -0.002845783019438386, 0.10389222949743271, 0.007167742121964693, -0.02981584332883358, 0.0637686476111412, -0.004013996105641127, -0.06481196731328964, -0.016571618616580963, 0.0567731037735939, -0.05724107846617699, 0.01837186887860298, -0.034018274396657944, 0.024836361408233643, -0.03744005411863327, 0.022137930616736412, 0.03853186219930649, -0.05844709649682045, 0.03434480354189873, -0.040261391550302505, -0.0036571614909917116, -0.03951416537165642, -0.05519435182213783, 0.05378478020429611, 0.02068929374217987, -0.03021388128399849, -0.020063303411006927, 0.10789480060338974, 0.0278102308511734, -0.0010252498323097825, -0.04921739175915718, 0.06172873452305794, 0.04519139230251312, -0.07962999492883682, -0.00030648059328086674, 0.08156245201826096, -0.013441435061395168, -0.06211588904261589, -0.02612893469631672, 0.1225050538778305, -0.00237522111274302, -0.03645600378513336, -0.057537514716386795, 0.050871118903160095, -0.006402662489563227, 0.05001795291900635, -0.020954525098204613, 0.01501664612442255, 0.10693485289812088, 0.12279579788446426, 0.06418971717357635, -0.08672042936086655 ]
there\tis\tevidence\tthat\tthe\tsperm\tepigenome\tis\trapidly\tremodeled\tafter\tweight\tloss\tfollowing\tbariatric\nsurgery\t(\nBlock\tand\tEl-Osta,\t2017\n).\tParental\tdiet,\tbody\tcomposition,\tmetabolism,\tand\tstress\texposure\nall\tappear\timportant,\n\tbut\tthe\teffects\tare\tsex-specific.\tMechanisms\tinclude\tepigenetic,\tcellular,\nphysiologic,\tand\tmetabolic\tchanges\t(
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physiologic,\tand\tmetabolic\tchanges\t(\nFleming\tet\tal,\t2018\n).\nNew\tresearch\talso\tis\tfocusing\ton\tthe\tgrandchildren\tof\tpeople\taffected\tby\tthe\tDutch\tfamine
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(\nRoseboom\tet\tal,\t2011\n)\tto\tdocument\tthe\tlong-term\tepigenetic\teffects\t(\nFig.\t14.4)\n.\tPreliminary\tresults\nshow\tthat\tunder-\tand\tovernutrition\tare\timportant\tissues,\tbut\tthere\tare\n\tdifferences\tin\tresponse\tby\nsex,\tand\tthe\ttiming\tof\tthe\tinsult\tmatters\t(\nVanhees\tet\tal,\t2014\n;\t\nPreston\tet\tal,\t2018\n).\nFIG.\t14.4
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Vanhees\tet\tal,\t2014\n;\t\nPreston\tet\tal,\t2018\n).\nFIG.\t14.4\nTransgenerational\tinheritance\tof\tepigenetic\tmodifications\tinduced\tby\texposure\tto\tmacro-\tand\nmicronutrients.\n\tSource:\t(Adapted\tfrom\tVanhees\tK,\tVonhögen\tIG,\tvan\tSchooten\tFJ\tet\tal:\tYou\tare\twhat\tyou\teat,\tand\tso\tare\tyour
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children:\tthe\timpact\tof\tmicronutrients\ton\tthe\tepigenetic\tprogramming\tof\toffspring,\t\nCell\tMol\tLife\tSci\n\t71:271,\t2014.)\nThe\tpreconceptual\tnutritional\trole\tin\taltering\tthe\n\tepigenome\tis\tstill\tbeing\tactively\texplored.\tAnimal\nresearch\tshows\tcomponents\tof\ta\tpreconceptual\tdiet\tmay\tresolve\ttoxicant\tepigenetic\tchanges\t(\nOwen\net\tal,\t2013
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Owen\net\tal,\t2013\n).\tMaternal\tand\tpaternal\tweight\tand\tnutritional\tstatus,\tas\twell\tas\tthat\tof\tprevious\ngenerations,\tare\tlikely\timportant\tin\taffecting,\tand\tbeing\taffected\tby,\tgenetic\tvariations.\tBecause\tof\nthe\tincreased\tappreciation\tfor\tthe\tpericonceptual\teffects\n\ton\tthe\tlifetime\thealth\tof\tthe\toffspring,
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on\tthe\tlifetime\thealth\tof\tthe\toffspring,\nthere\tare\tcalls\tfor\tmuch\tbetter\tguidance\tand\tparental\tpreparation\tbefore\tconception\t(\nFleming\tet\tal,\n2018\n)\t(see\t\nChapter\t6\n).\nNutrient\trequirements\tduring\tpregnancy\nNutrition\tduring\tpregnancy\toften\tis\tequated\twith\tweight\tgain\tbecause\tweight\tis\tmost\teasily\tand
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consistently\tmeasured.\tHowever,\tmaternal\tweight\tgain\tis\tnot\tnecessarily\tpredictive\tof\thealth\noutcomes,\tespecially\tfor\theavier\twomen.\tIn\tgeneral,\talthough\tthe\tmother\tneeds\tto\teat\ta\tlittle\tmore\nwhen\tshe\tis\tpregnant\tor\tbreastfeeding,\tshe\tneeds\tto\teat\tmore\tcarefully\tbecause\tmost\tnutrient
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requirements\tincrease\tmore\tduring\tpregnancy\tand\tlactation\tthan\tdo\tthe\tcalorie\trequirements\t(\nFig.\n14.5\n).\tThe\tU.S.\tdietary\treference\tintakes\t(DRIs)\tare\tfound\ton\tthe\tinside\tcover.\tEstimated\nrequirements\tduring\n\tpregnancy\tand\tlactation\tvary\tbetween\tcountries\t(see\tadditional\tinformation\ton
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the\tEvolve\twebsite\tfor\trecommendations\tfrom\tWHO\tand\t16\tgovernments\tor\tregions\tworldwide)\tbut\nthere\tis\ta\tcall\tto\timprove\tthe\tconsistency\tin\tthe\tdevelopment\tof\tthese\tvalues\tacross\tcultures\n(\nNational\tAcademies\tof\tSciences,\tEngineering,\tand\tMedicine,\t2018\n).\tFor\tmost\tnutrients,\tthere\tis\nlittle\tguidance\tby\ttrimester\tor\tfor
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).\tFor\tmost\tnutrients,\tthere\tis\nlittle\tguidance\tby\ttrimester\tor\tfor\n\tpregnancies\twith\tmore\tthan\tone\tfetus.\nFIG.\t14.5\nPercent\tof\tnonpregnant\tDRIs\tfor\tselected\tnutrients\tfor\tpregnancy\tand\tlactation.\tCalculations\tare\nbased\ton\ta\t25-year-old\twoman\t(65\tinches,\t126\tpounds\tprepregnant\tweight),\tpregnant\twith\ta\tsingleton\tin\tthe
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third\ttrimester\tand\tlactation\tin\tthe\tfirst\t6\tmonths.\nEnergy\nAdditional\tenergy\tis\trequired\tduring\tpregnancy\tto\tsupport\tthe\tmetabolic\tdemands\tof\tpregnancy\tand\nfetal\tgrowth.\tMetabolism\n\tincreases\tby\tan\taverage\tof\t15%\tin\tthe\tsingleton\tpregnancy,\tbut\twith\twide
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variability\tespecially\tin\tthe\tthird\ttrimester.\tThe\tDRI\tfor\tenergy\tincreases\tby\tonly\t340\tkcal/day\tduring\nthe\tsecond\ttrimester\tand\tby\t452\tkcal/day\tin\tthe\tthird\ttrimester.\tIf\tmaternal\tweight\tgain\tis\twithin\tthe\ndesirable\tlimits,\tthe\trange\tof\tacceptable\tenergy\tintakes\tvaries\twidely,\tgiven\tlarge\tindividual\ndifferences\tin\tenergy
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differences\tin\tenergy\n\toutput\tand\tbasal\tmetabolic\trate.\tModifying\tintakes\tto\tachieve\trecommended\nweight\tgain\t(see\t\nPregnancy\tWeight\tGain\tRecommendations\n)\tis\tmore\tuseful\tthan\tcalculating\tcaloric\nrequirements.\nExercise.\nEnergy\texpended\tin\tvoluntary\tphysical\tactivity\tis\tthe\tlargest\tvariable\tin\toverall\tenergy\texpenditure.
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Physical\tactivity\tincreases\tenergy\texpenditure\tproportional\tto\tbody\tweight.\tHowever,\tmost\tpregnant\nwomen\tcompensate\tfor\tincreased\tweight\tgain\tby\tslowing\ttheir\twork\tand\tmovement\tpace.\tTherefore\ntotal\tdaily\tenergy\texpenditure\tmay\tnot\tbe\tsubstantially\tgreater\tthan\tbefore\tpregnancy.
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The\tACOG\trecommends\tat\tleast\t20\tto\t30\tminutes\tof\tmoderate\tintensity\texercise\ton\tmost,\tif\tnot\tall,\ndays\tfor\tpregnant\twomen\twithout\tcontraindications\t(\nACOG,\t2015a\n).\tShort\tduration\tstrenuous\nexercise\tappears\tunconcerning,\n\tbut\tthe\timpact\tof\tlong\tduration\tstrenuous\texercise\ton\tthe\tfetus\tis\nunknown\t(\nSzymanski\tand\tSatin,\t2012
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unknown\t(\nSzymanski\tand\tSatin,\t2012\n).\tElite\tathletes\tmay\tneed\tto\tmodify\ttheir\texercise\troutines\t(\nBø\net\tal,\t2018\n).\tExcessive\texercise,\tcombined\twith\tinadequate\tenergy\tintake,\tmay\tlead\tto\tsuboptimal\nmaternal\tweight\tgain\tand\tpoor\tfetal\tgrowth.\tTherefore\ta\tpregnant\twoman\tshould\talways\tdiscuss\nexercise\twith\ther\thealth\tpractitioner.\tAlthough
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exercise\twith\ther\thealth\tpractitioner.\tAlthough\n\tthere\tis\tlimited\tevidence\tthat\texercise\thelps\tmodify\ngestational\tweight\tgain,\tthere\tis\talso\tno\tevidence\tof\tharm\tand\tin\tobservational\tstudies\texercise\thas\nbeen\tassociated\twith\tlower\trisk\tof\tgestational\tdiabetes,\tpregnancy-induced\thypertension,\tand\npreeclampsia\t(\nSeneviratne\tet\tal,\t2015
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preeclampsia\t(\nSeneviratne\tet\tal,\t2015\n).\tThe\teffect\tof\tmaternal\texercise\ton\toffspring\tsusceptibility\tto\nchronic\tdiseases\tis\tbeing\texplored\tin\tanimal\tresearch\n\tbut\tresults\tare\tmixed\tand\tthe\ttype,\ttiming,\nintensity,\tand\tdose\tof\toptimal\texercise\tare\tall\tunknowns\t(\nBlaize\tet\tal,\t2015\n).\tHowever,\tnot\tall
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Blaize\tet\tal,\t2015\n).\tHowever,\tnot\tall\nepigenetic\teffects\tmay\tbe\tpositive.\tThere\tis\tlimited\tevidence\tthat\texcessive\tpaternal\texercise\tis\nassociated\twith\tan\toffspring’s\tthrifty\tphenotype\t(\nDhasarathy\tet\tal,\t2017\n).\nProtein\nAdditional\tprotein\tis\trequired\tto\tsupport\tthe\tsynthesis\tof\tmaternal\tand\n\tfetal\ttissues.\tThis\tdemand
[ 0.005840352736413479, -0.06677987426519394, 0.07433150708675385, -0.003138576401397586, -0.06244603171944618, 0.0516626201570034, 0.08498699963092804, -0.0003683504764921963, -0.002948267851024866, 0.06695469468832016, 0.09897847473621368, -0.01905340701341629, 0.008213990367949009, 0.018184317275881767, -0.014191043563187122, 0.035888563841581345, -0.021099047735333443, 0.030652564018964767, -0.06328655779361725, -0.03652361407876015, 0.025064613670110703, 0.1023954451084137, 0.02883744426071644, 0.023130981251597404, 0.028665803372859955, 0.012815700843930244, -0.03224453330039978, -0.023854371160268784, 0.06622139364480972, -0.05868444964289665, -0.12470550090074539, 0.06289955228567123, 0.006167686078697443, -0.007577784359455109, 0.05141748487949371, 0.041273076087236404, -0.06462322175502777, 0.025762535631656647, 0.06454876810312271, 0.014840266667306423, -0.018419383093714714, -0.09294089674949646, -0.06811191886663437, 0.03498414531350136, 0.05779498443007469, 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fetal\ttissues.\tThis\tdemand\nincreases\tthroughout\tgestation\tand\tis\tmaximized\tduring\tthe\tthird\ttrimester.\tCaution\tis\tadvised\twhen\nreading\tthe\tDRI\ttables.\tThe\tbaseline\tprotein\tRDA\tof\t0.8\tg/kg\tcurrent\tbody\tweight/day\tfor\tpregnant\nwomen\tis\t46\tg\tonly\tfor\tsomeone\twith\ta\tprepregnant\tweight\tof\t126\tpounds.\tThe\tprotein\tcalculation\tin
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the\tfirst\thalf\tof\tpregnancy\tis\tthe\tsame\tas\tthat\tfor\tnonpregnant\twomen\tbut\n\tthe\trequired\tintake\nincreases\tas\tweight\tincreases.\tThe\tRDA\tcalculation\tincreases\tin\tthe\tsecond\thalf\tof\tpregnancy\tto\t1.1\ngm/kg\tcurrent\tbody\tweight/day.\tThis\twould\tbe\t71\tg/day\tonly\tfor\tthat\tsame\treference\twoman\twho\tis
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also\tgaining\tweight\tappropriately.\tFor\tmany\twomen,\tthe\tprotein\trequirement\tis\thigher.\tFor\teach\nadditional\tfetus,\tthe\tInstitute\tof\tMedicine\t(IOM)\trecommends\tan\tadditional\t50\tg/day\tstarting\n\tin\tthe\nsecond\ttrimester\t(\nOtten\tet\tal,\t2006\n),\tbut\tbecause\tprotein\tis\talso\tused\tas\tan\tenergy\tsource,\tthe\ttotal
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),\tbut\tbecause\tprotein\tis\talso\tused\tas\tan\tenergy\tsource,\tthe\ttotal\nmay\tbe\tas\tmuch\tas\t175\tg/day\tfor\tthe\tnormal-weight\twoman\tcarrying\ta\ttwin\tgestation\twho\tis\nconsuming\t3500\tkcal/day\t(\nGoodnight\tand\tNewman,\t2009\n).\nThe\tWHO\tuses\tslightly\tdifferent\tcalculations.\tThey\talso\tcalculate\ta\tbaseline\trequirement\tusing
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0.008183494210243225, -0.034062523394823074, -0.009066581726074219, 0.08544929325580597, 0.0804297924041748, -0.0668141171336174, -0.08095657080411911, 0.04940880089998245, 0.008238345384597778, -0.07834094762802124, -0.010038253851234913, 0.09765011817216873, -0.01712174341082573, -0.03685818985104561, -0.04020281136035919, 0.07499048858880997, 0.06638959050178528, -0.002976128598675132, -0.05872610583901405, 0.023594625294208527, 0.07398830354213715, 0.06548266112804413, 0.01056928001344204, -0.06837818771600723 ]
current\tbody\tweight.\tHowever,\tthe\testimates\tof\tincreased\n\tneeds\tare\tpresented\tas\tstandard\namounts/day\tfor\teveryone.\tThe\t2007\trecommendations\tare\tdesigned\tto\tsupport\ta\ttotal\t13.8\tkg\nweight\tgain.\tHowever,\tsome\tresearchers\trecommend\tthe\tolder\t(1985)\tand\tmore\tconservative\nguidelines\t(\nMillward,\t2012\n)\t(\nTable\t14.8\n).\nTABLE\t14.8
[ -0.08068531006574631, -0.0096157630905509, 0.08061112463474274, -0.002552029211074114, -0.055161915719509125, 0.022461608052253723, 0.027288302779197693, 0.007045216392725706, -0.017553646117448807, 0.02579857036471367, 0.07085658609867096, -0.022556886076927185, 0.010623902082443237, -0.0278905238956213, -0.08936905115842819, 0.023358022794127464, -0.07482344657182693, 0.01593952067196369, -0.0342022106051445, -0.019938500598073006, 0.00872955471277237, 0.09203246235847473, 0.05314693972468376, 0.014248011633753777, 0.03190208226442337, 0.04664512351155281, -0.11091934144496918, 0.038280121982097626, -0.020962776616215706, -0.05983205512166023, -0.1143418475985527, 0.062420591711997986, 0.014350241050124168, -0.00567155797034502, 0.08731282502412796, 0.036098189651966095, -0.01696486584842205, 0.04897317662835121, 0.04733923450112343, 0.02078435570001602, -0.021627113223075867, -0.09289892762899399, 0.0332210548222065, 0.02965126559138298, -0.02957010269165039, 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0.005742928478866816, -0.023078158497810364, -0.04320540279150009, -0.03790270537137985, -0.00020764469809364527, 0.02663181908428669, 0.018381038680672646, 0.01470141764730215, 0.06452105939388275, 0.092178575694561, 0.04386472702026367, -0.0956295058131218, -0.0053944638930261135, 0.01318405382335186, -0.09364401549100876, -0.05730709433555603, 0.01431228406727314, 0.022906271740794182, -0.02186676859855652, -0.020429221913218498, 0.06348506361246109, 0.022199466824531555, 0.06234616041183472, 0.04395632445812225, 0.03143569827079773, -0.1064990758895874, -0.04357205703854561, -0.054782070219516754, -0.036558978259563446, -0.05984791740775108, -0.019810553640127182, -0.03423100337386131, 0.022075418382883072, -0.10610262304544449, 0.06074105203151703, -0.04366825148463249, 0.044198036193847656, 0.009597607888281345, -0.10070881992578506, 0.005200399085879326, -0.00955241173505783, -0.051284413784742355, -0.11147771030664444, -4.32451955508439e-33, -0.006185353267937899, 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0.05548235774040222, 0.09300781786441803, 0.044762011617422104, -6.698125076809447e-8, -0.006186018232256174, 0.0008111325441859663, -0.008924206718802452, 0.008081113919615746, 0.049862489104270935, 0.0005348124541342258, 0.04736711457371712, 0.013510475866496563, -0.020374562591314316, -0.038510214537382126, 0.1471906453371048, -0.01804175227880478, -0.07573657482862473, -0.04907624423503876, 0.03145869821310043, -0.021075624972581863, -0.05537106841802597, 0.14715003967285156, -0.05460626259446144, -0.09741495549678802, 0.016823912039399147, 0.08871661871671677, 0.02972855232656002, -0.04117165505886078, -0.050999194383621216, 0.02433980628848076, -0.043713074177503586, 0.0015597924357280135, -0.02255507931113243, 0.05776653811335564, 0.03266085684299469, 0.006895645521581173, 0.03676679730415344, -0.08730682730674744, -0.00035618868423625827, 0.065252885222435, -0.07587976008653641, -0.02266955003142357, -0.04118731990456581, 0.09763839840888977, -0.02661428414285183, 0.007115781307220459, -0.028663674369454384, 0.10297926515340805, 0.11190871149301529, -0.06116914004087448, -0.04787147417664528, 0.02521885372698307, -0.017227886244654655, -0.0585721917450428, 0.03098486177623272, 0.05728147178888321, 0.028989285230636597, 0.002693494316190481, -0.06565206497907639, 0.05991800129413605, 0.024844970554113388, 0.07653681933879852, -0.050102803856134415, -0.0011629307409748435, 0.0881916731595993, 0.01797904446721077, 0.014833515509963036, 0.0103013776242733 ]
guidelines\t(\nMillward,\t2012\n)\t(\nTable\t14.8\n).\nTABLE\t14.8\nProtein\tIntake\tRecommendations\nPrepregnancy\nFirst\nTrimester\nSecond\tTrimester\nThird\nTrimester\nNotes\nU.S.\nDRIs\n0.8\tg/kg\ncurrent\nbody\nweight/day\n0.8\tg/kg\ncurrent\nweight/day\n1.1\tg/kg\tcurrent\tweight/day\nstarting\tin\tthe\tsecond\nhalf\tof\tpregnancy\n1.1\tg/kg\ncurrent\nweight/day\nWHO,\n2007\n0.83\tg/kg
[ -0.03539188206195831, 0.030758488923311234, 0.007787511218339205, 0.028378602117300034, -0.0955442488193512, 0.018652552738785744, -0.02592037059366703, 0.05057641491293907, -0.10919317603111267, 0.018978945910930634, 0.09821318835020065, -0.09758023172616959, -0.060601409524679184, -0.0469609797000885, -0.04980358108878136, -0.06271813064813614, 0.033990707248449326, -0.028647324070334435, -0.07394693046808243, -0.028263218700885773, 0.05009923502802849, 0.023616047576069832, 0.05275426059961319, -0.01448106300085783, 0.01635381579399109, -0.068599171936512, -0.05887875705957413, 0.005316664930433035, -0.03216337785124779, 0.025169435888528824, -0.060209523886442184, 0.00626986613497138, 0.05063953623175621, 0.021436838433146477, -0.03670169785618782, -0.03682103753089905, 0.025533432140946388, -0.007012377958744764, -0.0531114898622036, 0.07478051632642746, 0.002531053964048624, -0.03325912356376648, -0.05301815643906593, 0.011007627472281456, 0.027433184906840324, 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half\tof\tpregnancy\n1.1\tg/kg\ncurrent\nweight/day\nWHO,\n2007\n0.83\tg/kg\ncurrent\nbody\nweight/day\nBaseline\t+\n0.7\tg/day\nBaseline\t+\t9.6\tg/day\nBaseline\t+\n31.2\tg/day\nWHO,\n1985\n0.83\tg/kg\ncurrent\nbody\nweight/day\nBaseline\t+\n1.2\tg/day\nBaseline\t+\t6.1\tg/day\nBaseline\t+\n10.7\tg/day\nAverage\tincrease\t6\ng/day\tabove\nbaseline\nrequirements
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10.7\tg/day\nAverage\tincrease\t6\ng/day\tabove\nbaseline\nrequirements\nAdapted\tfrom\tMillward\tDJ:\tIdentifying\trecommended\tdietary\tallowances\tfor\tprotein\tand\tamino\tacids:\ta\tcritique\tof\tthe\t2007\tWHO/FAO/UNU\treport,\nBr\tJ\tNutr\n\t108(Suppl\t2):S3,\t2012.\nThere\tis\tconcern\tthat\tnitrogen\tbalance\tstudies\tmay\tunderestimate\tprotein\tneeds,\tespecially\twhen\nconsidering
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considering\n\tthat\tthe\tincreased\trequirements\tof\tspecific\tamino\tacids\tmay\tbe\tdisproportionately\nhigher\taccording\tto\tanimal\tresearch\t(\nElango\tand\tBall,\t2016\n).\tThere\tis\tsome\tcall\tto\tincrease\tprotein\nrequirements,\tincluding\tincreasing\tthe\tprotein\tintake\tearlier\tin\tpregnancy.\tRecent\tresearch\tfound
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optimal\tintake\twas\t1.2\tg/kg/day\tat\t16\tweeks\tand\t1.52\tg/kg/day\tat\t36\tweeks\twhen\testimated\tby\nindicator\tamino\tacid\toxidation.\n\tHowever,\tthe\tmethod\tis\tnot\tuniversally\taccepted\tand\tfurther\nresearch\tis\tnecessary.\tProtein\tdeficiency\tduring\tpregnancy\thas\tadverse\tconsequences,\tincluding
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poor\tfetal\tgrowth.\tProtein\talso\tis\tinvolved\tin\tthe\tsynthesis\tof\thormones\tand\tneurotransmitters.
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paid,\tincluding\tthose\tconsuming\ta\tvegetarian\tdiet,\tthose\twho\tare\tstill\tgrowing\tthemselves,\tor\tthose\nwho\tare\tpregnant\twith\tmultiples.\tThe\toptimal\tbalance\tof\tprotein\tto\ttotal\tcalories\thas\tyet\tto\tbe\ndetermined\tand\trecommendations,\tas\twell\tas\tintakes,\tvary\n\tacross\tcultures\t(\nBlumfield\tand\tCollins,\n2014
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the\tmechanism\tis\tunclear.\tCurrent\tU.S.\tpractice\toften\ttargets\tprotein\n\tintakes\tat\t20%\tof\ttotal\ncalories,\tpossibly\thigher\tfor\tmultiples.\tWHO\trecommends\t23%\tof\tcalories\tcome\tfrom\tprotein\n(\nMillward,\t2012\n).\tSupplementation,\tif\tnecessary,\tshould\tbe\tdone\twith\tfood\trather\tthan\twith\tprotein
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supplements.\tFor\texample,\tsomeone\tconsuming\t2240\tkcal\tfrom\t6\tcups/day\tof\t2%\tmilk,\t8\toz\tof\tmeat,\nsix\tservings\tof\tstarch,\tthree\tvegetable\tservings,\ttwo\tfruit\tservings,\tand\tsix\tfat\tservings\n\tgets\t23%\tof\ncalories\tfrom\tprotein\t(128\tg).\tIf\tusing\tskim\tmilk,\tthe\ttotal\tis\t1970\tkcal\twith\t26%\tfrom\tprotein.\nCarbohydrates
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0.0008200622978620231, -0.025968702509999275, 0.11211198568344116, 0.11055450141429901, -4.283279508854321e-8, 0.05538535863161087, -0.01574079319834709, -0.02692718431353569, -0.05672336742281914, 0.0477164126932621, -0.04489365965127945, 0.045184653252363205, 0.05475488677620888, 0.015510638244450092, -0.026287628337740898, -0.01663178950548172, 0.16020435094833374, -0.030686717480421066, 0.0023882505483925343, 0.0018831654451787472, 0.030836360529065132, 0.038935549557209015, 0.06295923888683319, -0.0086519755423069, -0.06164337322115898, -0.021283045411109924, 0.020242802798748016, -0.03991585969924927, 0.018534697592258453, -0.03725901618599892, -0.023477770388126373, 0.028116339817643166, 0.018933003768324852, 0.050175249576568604, 0.019287211820483208, 0.10378525406122208, -0.008726464584469795, 0.010534428991377354, -0.04826978221535683, -0.022211194038391113, 0.030129266902804375, -0.020160535350441933, -0.02172772027552128, -0.03038191981613636, 0.09227485209703445, 0.005182439927011728, -0.03954024612903595, 0.019633101299405098, 0.06511560827493668, 0.04560352489352226, -0.10293643176555634, 0.0008582083391956985, 0.09697727859020233, -0.002661831444129348, -0.05527764931321144, -0.038452982902526855, 0.10337325185537338, -0.0062175532802939415, -0.007583118509501219, -0.00872556958347559, 0.030190512537956238, 0.0875835120677948, 0.008723794482648373, -0.0031346504110842943, 0.006771919317543507, 0.05878451094031334, 0.10052946954965591, 0.10021790862083435, -0.018964672461152077 ]
should\tbe\ngiven\tto\tcomplex\tcarbohydrates\tfrom\twhole\tgrains,\tfruits,\tand\tvegetables\trather\tthan\tjust\tsimple\nsugars,\tincluding\trefined\tliquid\tsugars,\twhether\tnatural\t(juices)\tor\tindustrially\tproduced\t(soda).\nFiber\nDaily\tconsumption\tof\twhole-grain\tbreads\tand\tcereals,\tleafy\tgreen\tand\tyellow\tvegetables,\tand\tfresh
[ -0.05576038360595703, -0.04583883285522461, 0.05094023048877716, -0.05796331912279129, -0.07821690291166306, 0.0016462525818496943, 0.09456060826778412, -0.008475350216031075, -0.015766451135277748, 0.021830134093761444, 0.09173987805843353, -0.033775512129068375, 0.07489067316055298, 0.023830130696296692, -0.009283375926315784, 0.008566748350858688, 0.011992731131613255, 0.06094028055667877, -0.07633744925260544, -0.08893987536430359, 0.057249244302511215, 0.0729425773024559, 0.031952742487192154, 0.027409102767705917, 0.042116619646549225, 0.08607199788093567, -0.06652189791202545, -0.026171134784817696, 0.012805747799575329, -0.06213090941309929, -0.09314058721065521, 0.06816302984952927, -0.031638018786907196, -0.02317854017019272, 0.028289319947361946, 0.01029048953205347, -0.04110991954803467, 0.01824316568672657, 0.017353568226099014, 0.010880837216973305, -0.06120818480849266, -0.07582797855138779, -0.03502111881971359, 0.017425237223505974, 0.040294893085956573, 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-0.09572333842515945, -0.08440349251031876, -0.06363248080015182, 0.05513952672481537, 0.08601073175668716, -0.018825095146894455, -0.023839645087718964, -0.013850037939846516, 0.03971506282687187, 0.022170495241880417, 0.029505474492907524, -0.09328105300664902, -0.09158920496702194, -0.0455932691693306, -0.03487645834684372, 0.023608941584825516, 0.09198937565088272, -0.0711853876709938, 0.06739477813243866, -0.07795290648937225, -0.0015715848421677947, 0.0033238008618354797, 0.01717386208474636, -0.08185651153326035, 0.03306356444954872, -0.01752421259880066, -0.07021064311265945, -0.15094387531280518, 0.04238215833902359, -0.012057668529450893, 0.049252450466156006, -0.02713637799024582, -0.06960234045982361, 0.0036418817471712828, -0.026694530621170998, 0.03945695608854294, 0.024507632479071617, -0.015277907252311707, -0.0013409563107416034, -0.02302970550954342, 0.013712428510189056, -0.0043195015750825405, 0.05709857493638992, 0.11611462384462357, -0.03984197601675987, 0.06400075554847717, 0.09280059486627579, 0.09415712207555771, 0.05430057272315025, -5.545841474940971e-8, -0.028934288769960403, -0.04335549846291542, -0.022647574543952942, 0.060162290930747986, 0.02993657812476158, -0.027323853224515915, 0.06950124353170395, 0.040237169712781906, -0.04330378398299217, -0.08944742381572723, 0.034874625504016876, 0.09734021127223969, -0.08737041801214218, -0.01212399173527956, 0.04868580773472786, 0.006091575603932142, -0.002799989888444543, 0.041872572153806686, -0.06031369790434837, -0.029492007568478584, -0.0034570132847875357, 0.08758014440536499, -0.031985558569431305, 0.0096861207857728, -0.030507458373904228, 0.01382382120937109, -0.013436086475849152, 0.051253680139780045, 0.02655671164393425, 0.03532195836305618, 0.04088584706187248, -0.04163731634616852, -0.025860680267214775, -0.027014855295419693, -0.030437391251325607, 0.01832219958305359, -0.04431462287902832, -0.03092503733932972, -0.0005903335986658931, 0.09363594651222229, -0.035915449261665344, -0.0017263733316212893, -0.021594557911157608, 0.0870116800069809, 0.0554269477725029, -0.0809655636548996, -0.015384034253656864, 0.08435595780611038, -0.006926290225237608, -0.03208295628428459, 0.007298262789845467, 0.08329214155673981, 0.014909328892827034, -0.027195561677217484, 0.023699291050434113, 0.026361748576164246, 0.06504109501838684, 0.033525679260492325, -0.0390956774353981, -0.015103268437087536, 0.045545794069767, 0.06287816911935806, 0.08748006820678711, -0.06031050160527229 ]
and\tdried\tfruits\tshould\tbe\tencouraged\tto\tprovide\tadditional\tminerals,\tvitamins,\tand\n\tfiber.\tThe\tDRI\nfor\tfiber\tduring\tpregnancy\tis\t14\tg/day/1000\tkcal\tand,\tif\tmet,\twill\thelp\ta\tgreat\tdeal\tin\tmanaging\tthe\nconstipation\tthat\toften\taccompanies\tpregnancy.\nLipids
[ -0.028629573062062263, 0.013455294072628021, 0.0484510138630867, 0.019616935402154922, -0.05858910083770752, 0.034215234220027924, 0.1173209622502327, 0.0481005497276783, -0.00026775154401548207, 0.019793931394815445, 0.15882965922355652, -0.05187602713704109, -0.008340779691934586, -0.009715033695101738, 0.0059068710543215275, 0.043575186282396317, 0.00006983692583162338, -0.006306050345301628, -0.020270174369215965, 0.010058014653623104, 0.02223965711891651, 0.05511591583490372, 0.05417914688587189, 0.0008534929365850985, 0.044486984610557556, -0.00651487335562706, -0.04776735231280327, -0.028505586087703705, -0.02129943110048771, 0.02155422791838646, -0.07817194610834122, 0.1115926131606102, -0.008978537283837795, 0.012865998782217503, 0.020657522603869438, -0.023036830127239227, -0.09322413802146912, 0.04703187197446823, 0.06363117694854736, 0.041514258831739426, 0.01938604563474655, -0.11529658734798431, -0.05696944519877434, 0.024637682363390923, 0.03136206045746803, 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constipation\tthat\toften\taccompanies\tpregnancy.\nLipids\nAs\twith\tnonpregnant\twomen,\tthere\tis\tno\tDRI\tfor\ttotal\tlipids\tduring\tpregnancy.\tThe\tamount\tof\tfat\tin\nthe\tdiet\tshould\tdepend\ton\tenergy\trequirements\tfor\tproper\tweight\tgain.\tHowever,\trecommendations\nfor\tomega-6\tpolyunsaturated\n\tfatty\tacid\t(PUFA)\t(linoleic\tacid)\tand\tomega-3\tPUFA\t(alpha-linolenic
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fatty\tacid\t(PUFA)\t(linoleic\tacid)\tand\tomega-3\tPUFA\t(alpha-linolenic\nacid)\tincrease\tslightly.\tAlthough\tnot\ta\tDRI,\tthe\trecommended\tintake\tof\tDHA\tis\t200\tmg/day\tand\tcan\nbe\tmet\tby\tone\tto\ttwo\tportions\tof\tfish\tper\tweek\t(\nCarlson\tet\tal,\t2017\n)\t(see\t\nFocus\tOn:\n\tOmega-3\tFatty\nAcids\tin\tPregnancy\tand\tLactation\n).\nVitamins
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0.047825396060943604, -0.03744060918688774, 0.08994802087545395, 0.11133749783039093, -4.702430800307411e-8, 0.08650477975606918, -0.033005330711603165, -0.009350872598588467, -0.012071878649294376, 0.039226047694683075, -0.0597919337451458, 0.014853302389383316, 0.011563190259039402, 0.06837155669927597, -0.07372751832008362, -0.0020201837178319693, 0.12453481554985046, -0.05803445354104042, -0.023527175188064575, 0.035049643367528915, 0.0393487811088562, -0.024383796378970146, 0.10654892027378082, -0.01720263995230198, -0.13615010678768158, -0.03109809383749962, 0.04309109225869179, -0.0020615393295884132, -0.0035854533780366182, -0.03564987704157829, -0.02397589012980461, 0.00556666124612093, 0.03295598551630974, 0.0727388858795166, 0.06419295072555542, 0.08156237006187439, -0.042895324528217316, 0.01582515612244606, -0.05162213742733002, -0.011004188098013401, 0.04124217480421066, -0.010335706174373627, -0.05041822791099548, -0.06157365441322327, 0.18052498996257782, 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Focus\tOn:\n\tOmega-3\tFatty\nAcids\tin\tPregnancy\tand\tLactation\n).\nVitamins\nAll\tvitamins\tand\tminerals\tare\tneeded\tfor\toptimal\tpregnancy\toutcome.\tIn\tsome\tinstances\nrequirements\tmay\tbe\tmet\tthrough\tdiet.\tFor\tothers\ta\tsupplement,\tstarted\tpreconceptually,\tis\toften
[ -0.009988418780267239, -0.07495970278978348, 0.003984966780990362, 0.022343575954437256, -0.041414301842451096, 0.04412108659744263, 0.12896694242954254, 0.054981887340545654, -0.03054719604551792, 0.03153739869594574, 0.11982688307762146, -0.045477114617824554, -0.0343376100063324, -0.023257063701748848, -0.0032952935434877872, 0.053784675896167755, -0.013074303977191448, 0.011225676164031029, -0.04675443470478058, -0.01121576875448227, 0.060233891010284424, 0.06213802471756935, 0.035387296229600906, -0.0021145332138985395, 0.03888166695833206, -0.013079464435577393, -0.05505780875682831, -0.042176902294158936, -0.003584542777389288, -0.010462695732712746, -0.03361073136329651, 0.06923732906579971, 0.046912699937820435, -0.01091762911528349, 0.002255310071632266, 0.01576593518257141, -0.10609623044729233, 0.015415521338582039, 0.024084750562906265, 0.013437562622129917, -0.010602332651615143, -0.06599726527929306, -0.06639530509710312, 0.007120722904801369, 0.05761519446969032, 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-0.029444824904203415, -0.0018825379665941, 0.03273933380842209, 0.10137668997049332, 0.03677263483405113, -0.060227662324905396, 0.013150247745215893, 0.04758273810148239, -0.0006818829569965601, -0.0488150455057621, -0.010560237802565098, 0.08711015433073044, 0.040743034332990646, 0.0036096610128879547, -0.09173929691314697, 0.05862095206975937, 0.10506731271743774, 0.008988744579255581, -0.030551457777619362, -0.027519147843122482, 0.0669436827301979, 0.05811842158436775, 0.06564944237470627, 0.010787985287606716 ]
necessary.\tMany,\tbut\tnot\tall,\tvitamin\tand\tmineral\trecommendations\tincrease\twith\tpregnancy,\tbut\tthe\nmagnitude\tof\tthe\tincrease\tvaries\tby\tnutrient\t(see\tthe\tDRI\ttables\ton\tthe\tinside\tcover\tand\t\nFig.\t14.5\n).\nFolate.\nThe\tRDA\tfor\tdietary\tfolate\tequivalents\tincreases\tto\tsupport\tmaternal\terythropoiesis,\tDNA\n\tsynthesis,
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synthesis,\nand\tfetal\tand\tplacental\tgrowth.\tLow\tfolate\tlevels\tare\tassociated\twith\tmiscarriages,\tLBW,\tand\npreterm\tbirth.\tEarly\tmaternal\tfolate\tdeficiency\tis\tassociated\twith\tan\tincreased\tincidence\tof\ncongenital\tmalformations,\tincluding\tNTDs,\torofacial\tclefts,\tand\tcongenital\theart\tdefects\t(\nObeid\tet\tal,\n2013
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Obeid\tet\tal,\n2013\n).\tApproximately\t3000\tnew\tcases\tof\tNTDs\toccur\tin\tthe\tUnited\tStates\tannually\tand\tover\t300,000\nbabies\tare\tborn\tworldwide\twith\tNTDs\t(\nCDC,\t2018a\n),\tbut\tprevalence\tvaries\twidely,\tfrom\t6.9/10,000\nbirths\tin\tthe\tWestern\tPacific\tto\t21.9/10,000\tbirths\tin\tthe\tMiddle\tEast\t(\nACOG,\t2017b\n).\tAlthough\tspina
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0.020067576318979263, -0.04681278392672539, -0.024577677249908447, 0.08964668959379196, 0.0786706954240799, -0.09349320828914642, -0.09297307580709457, 0.06443049758672714, -0.022557690739631653, -0.0745609849691391, -0.022870026528835297, 0.10127047449350357, -0.020611640065908432, -0.004961180500686169, 0.01377451978623867, -0.018611880019307137, -0.03039536252617836, -0.023543931543827057, -0.054172664880752563, 0.09676338732242584, 0.11301388591527939, 0.0030326482374221087, 0.07405289262533188, 0.0019954275339841843 ]
ACOG,\t2017b\n).\tAlthough\tspina\nbifida\tand\tanencephaly\tare\tthe\tmost\tcommon,\tother\tNTDs\tcan\talso\toccur\t(\nTable\t14.9\n).\tThe\tneural\ntube\tcloses\tby\t28\tdays\tof\tgestation,\tbefore\tmost\twomen\trealize\tthey\tare\tpregnant.\tIn\taddition,\tmore\nthan\n\thalf\tof\tall\tU.S.\tpregnancies\tare\tunplanned.\tTherefore\tthe\tCDC\trecommends\tthat\tall\twomen\tof
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0.050975166261196136, -0.03758595883846283, -0.0019581536762416363, 0.07882793247699738, 0.05491899698972702, -0.09308770298957825, 0.011723066680133343, 0.06923211365938187, -0.012607285752892494, -0.04738995060324669, -0.031079713255167007, 0.12159591168165207, 0.06273744255304337, -0.0586920790374279, 0.009787715040147305, 0.008503004908561707, 0.03462674841284752, 0.030608100816607475, -0.04936007782816887, 0.033208273351192474, 0.1113906130194664, 0.09182673692703247, 0.06379864364862442, -0.024371113628149033 ]
childbearing\tage,\tin\tanticipation\tof\tpossible\tpregnancy,\tincrease\ttheir\tintake\tof\tfolic\tacid\tby\t400\nmcg/day,\tthe\tsynthetic\tversion\tthat\tis\tavailable\tin\tsupplements\tand\tfortified\tfoods,\tespecially\tsome\nbreakfast\tcereals\t(\nCDC,\t2018a\n).\tThe\tU.S.\tPreventive\tServices\tTask\tForce\t(USPSTF)\trecommends\t400\nto\t800\tmcg/day
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to\t800\tmcg/day\n\tof\tfolic\tacid\tpreconceptually.\tWomen\twho\thave\thad\ta\tprevious\tNTD-affected\npregnancy\tshould\tconsume\t400\tmcg/day\twhen\tnot\tplanning\tto\tconceive\tand\tthose\tplanning\npregnancy\tshould\tconsider\t4000\tmcg/day\t(4\tmg/day)\tfrom\t3\tmonths\tbefore\tto\t3\tmonths\tafter\nconception\t(\nACOG,\t2017b
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conception\t(\nACOG,\t2017b\n).\tOther\tsituations\tthat\tmay\tmerit\tthe\thigher\tsupplementation\tlevels\ninclude\twomen\twho\thave\tan\tNTD\tthemselves,\twhose\tpartner\n\thas\tan\tNTD,\tor\twhose\tpartner\thas\ta\npreviously\taffected\tchild.\tThese\thigher\tdoses\tshould\tbe\ttaken\tas\ta\tseparate\tsupplement\tand\tnot\tas
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equally\teffective\tin\npreventing\trecurrent\tNTDs\t(\nDolin\tet\tal,\t2018\n).\tSupplementation\trecommendations\tvary\tby\tcountry\n(\nMoussa\tet\tal,\t2016\n)\tand\tmay\ttake\tthe\tgenetic\tsusceptibility\tto\tlow\tfolate\tstatus\tinto\taccount\t(\nColson\net\tal,\t2017\n)\tso\tlocal\tguidelines\tshould\tbe\tfollowed.\tAlthough\tthe\t800-mcg\tdose\tachieves
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recommended\tblood\tlevels\tin\t4\tweeks,\tthe\t400-mcg\tdose\trequires\t8\tto\t12\tweeks\tto\treach\tthese\nlevels\t(\nBerti\tet\tal,\t2011\n).\tAlso\tavailable\tis\t5-methyltetrahydrofolate,\tthe\tprimary\tcirculating\tform\tof\nfolate.\tIt\tis\tproposed\tto\tbe\tbetter\tused,\tespecially\tby\tthose\twith\tpolymorphisms\t(see\t\nChapter\t6\n),\tand
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Chapter\t6\n),\tand\nwithout\tthe\tdetrimental\trise\tin\tunmetabolized\tfolic\tacid.\tHowever,\tits\trole\tin\tpreventing\tNTDs\tor\nother\tbirth\tdefects\tis\tuntested\tin\tclinical\ttrials\t(\nObeid\tet\tal,\t2013\n).\tIn\taddition,\tconcern\n\tabout\nunmetabolized\tfolic\tacid\tmay\tbe\tunwarranted\tin\tsome\tcases,\tas\tit\twas\tfound\tto\tbe\tundetectable\tif
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pregnant\twomen\ttook\t400\tmcg/day\tthroughout\tthe\tpregnancy,\tin\taddition\tto\tconsuming\t100\tmcg/day\nfrom\tfortified\tgrains,\teven\tamong\tthose\twith\tthe\tC677T\tpolymorphism\t(\nPentieva\tet\tal,\t2016\n).\tThe\nimpact\tof\thigher\tdoses\tof\tfolic\tacid\tcausing\thigher,\tand\tconcerning,\tlevels\tof\tunmetabolized\tfolic\tacid\nis\tnot\twell-established\tbut\tis\tbeing\tstudied\t(
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is\tnot\twell-established\tbut\tis\tbeing\tstudied\t(\nPlumptre\tet\tal,\t2015\n).\nTABLE\t14.9\nNeural\tTube\tDefects\nNeural\tTube\nDefect\nMalformation\nCranial\nAnencephaly\nFailure\tof\tfusion\tof\tcephalic\tportion\tof\tneural\tfolds;\tabsence\tof\tall\tor\tpart\tof\tbrain,\nskull,\tand\tskin\nEncephalocele
[ 0.027128860354423523, -0.08132811635732651, 0.04319891333580017, -0.05493558943271637, -0.11460614204406738, 0.04061562567949295, 0.0556144155561924, 0.033256158232688904, 0.018492450937628746, 0.08607584238052368, 0.07118426263332367, -0.022062305361032486, 0.012880923226475716, 0.051578588783741, -0.08862794935703278, -0.0080063845962286, -0.05547915771603584, -0.021092819049954414, -0.057680435478687286, 0.004456854425370693, -0.003340241266414523, 0.10068480670452118, 0.02187390625476837, -0.04367480427026749, 0.05079108476638794, 0.03675522282719612, -0.0929279550909996, -0.028683697804808617, 0.021463707089424133, -0.058245234191417694, -0.0910990834236145, 0.03881397843360901, -0.00504501536488533, -0.03600016236305237, 0.052260976284742355, 0.036312349140644073, -0.01314474456012249, 0.021171443164348602, 0.06952399015426636, 0.039753664284944534, 0.002641304861754179, -0.0690513625741005, -0.07060819864273071, 0.04242546483874321, 0.051804304122924805, 0.022212516516447067, 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skull,\tand\tskin\nEncephalocele\nFailure\tof\tcomplete\tskull\tformation;\textrusion\tof\tbrain\ttissue\tinto\tmembranous\tsac\nExencephaly\nFailure\tof\tscalp\tand\tskull\tformation;\texteriorization\tof\tabnormally\tformed\tbrain\nIniencephaly\nDefect\tof\tcervical\n\tand\tupper\tthoracic\tvertebrae;\tabnormally\tformed\tbrain\ttissue\tand\nextreme\tretroflexion\tof\tupper\tspine\nSpinal
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extreme\tretroflexion\tof\tupper\tspine\nSpinal\nCraniorachischisis\nCoexisting\tanencephaly\tand\topen\tneural\ttube\tdefect,\toften\tin\tthe\tcervical–thoracic\nregion\nHolorachischisis\nFailure\tof\tfusion\tof\tvertebral\tarches;\tentire\tspinal\tcord\texposed\nMeningocele\nFailure\tof\tfusion\tof\tcaudal\tportion\tof\tneural\ttube;\tmeninges\texposed\nMyelomeningocele
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Myelomeningocele\nFailure\tof\tfusion\tof\tcaudal\tportion\tof\tneural\ttube;\tmeninges\tand\tneural\ttissue\texposed\nMyeloschisis\nFailure\tof\tfusion\tof\tcaudal\tportion\tof\tneural\ttube;\tflattened\tmass\tof\tneural\ttissue\nexposed\nSpina\tbifida\nFailure\tof\tfusion\tof\tcaudal\tportion\tof\tneural\ttube,\tusually\tof\t3-5\tcontiguous\tvertebrae;
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fewest\tNTDs\t(\nObeid\tet\tal,\t2013\n),\talthough\tthe\tmechanism\tof\tfolic\tacid\tis\tstill\tunknown\t(\nACOG,\n2017b\n).\tNatural\tfolate\tis\tless\tbioavailable\tand\thas\tnot\tbeen\tshown\n\tto\traise\tblood\tlevels\tas\twell\tas\tthe\nsynthetic\tfolic\tacid\tor\tto\tlower\tthe\trisk\tof\tNTDs.\tAlthough\ttheoretically\tnatural\tfolate\tcould\tbe
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effective,\t6\tto\t12\tcups\tof\traw\tspinach\t(more\tthan\t2\tcups\tcooked)\tdaily\tis\tthe\tbioequivalent\tlevel\tof\nnatural\tfolate\tthat\tis\tfound\tin\tone\tbowl\tof\tfortified\tbreakfast\tcereal.\tLook\tfor\t100%\tof\tthe\tdaily\nvalue/serving.\nWomen\twho\tare\tobese\tor\twho\tsmoke,\tconsume\talcohol\n\tmoderately\tor\theavily,\tor\tuse\trecreational
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moderately\tor\theavily,\tor\tuse\trecreational\ndrugs\tare\tat\trisk\tfor\tmarginal\tfolate\tstatus,\tas\tare\tthose\twith\tmalabsorption\tsyndromes\tor\tgenetic\ndifferences\trelated\tto\tmethylation\tand\tthe\tmetabolic\tuse\tof\tdietary\tfolate,\tincluding\tthe\testimated\n11%\tof\tthe\tU.S.\tpopulation\twith\tthe\tMTHFR\t677\tC\tto\tT\tvariation\t(\nCaudill,\t2010\n).\tEuropean
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Caudill,\t2010\n).\tEuropean\nprevalence\tis\testimated\tto\tbe\t10%\tto\t22%\t(\nObeid\tet\tal,\t2013\n),\tbut\n\tnot\tall\tpopulations\twith\tthe\tC677T\npolymorphism\tshow\thigher\trates\tof\tNTDs\t(\nACOG,\t2017b\n).\tOther\tpolymorphisms\tare\talso\tbeing\ninvestigated\tfor\tincreased\trisk\tfor\tNTDs.\tAlthough\tincreased\tfolate\tintake\tmay\tbe\thelpful\tin\tsome
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situations,\tadded\triboflavin\talso\tmay\tbe\tbeneficial\t(see\t\nChapters\t5\n\tand\t\n6\n).\tWomen\tusing\tantiseizure\nmedications\tmust\tbe\tmonitored\tclosely\twhen\tstarting\tfolic\tacid\tbecause\tit\n\tcan\treduce\ttheir\tseizure\ncontrol.\nEnriched\tgrain\tproducts\tin\tthe\tUnited\tStates\tare\tfortified\twith\tfolic\tacid\tand\tare\testimated\tto
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provide\tan\taverage\t200\tmcg/day,\twith\tresulting\thigher\tblood\tfolate\tlevels\tand\treduced\t(19%\tto\t54%)\nNTD\trates\t(\nCaudill,\t2010\n).\tHowever,\twith\tthe\tincreased\tpopularity\tof\tthe\tlow\tcarbohydrate\tdiets,\nestimated\tintake\thas\tbeen\treduced\trecently\tand\tis\tassociated\twith\tincreased\n\trisk\tof\tNTDs\n(\nDesrosiers\tet\tal,\t2018
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risk\tof\tNTDs\n(\nDesrosiers\tet\tal,\t2018\n).\tBecause\tNTD\trates\tremain\thigher\tamong\tthe\tHispanic\tpopulation\tin\tthe\nUnited\tStates,\tfortification\tof\tcorn\tmasa\tflour\tis\tnow\tapproved\tby\tthe\tFDA\tbut\timplementation\tis\nvoluntary\tand\tnot\twidespread.\nOver\t70\tcountries\tnow\tfortify\tgrain\tproducts\tbut\tthis\tfortification\tis\tnot\tuniversally\tpracticed
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because\tof\tconcerns\tabout\texposing\tthe\tentire\tpopulation\tto\textra\n\tfolic\tacid.\tPossible\tadverse\teffects\nof\tincreased\tfolic\tacid\tintake\tinclude\tmasking\tof\tvitamin\tB\n12\n\tdeficiency,\ttumor\tpromotion,\tepigenetic\nhypermethylation,\tinterference\twith\tantifolate\ttreatments,\tand\tan\tincrease\tin\tmiscarriages\tand
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multiple\tbirths.\tWidespread\tproblems\thave\tnot\tbeen\tseen.\tHowever,\thigh\tintakes\tof\tfolic\tacid\talso\nhave\tpotential\tepigenetic\teffects,\tbut\tdata\tare\tfragmentary\tand\n\tsometimes\tconflicting.\tCaution\tis\nadvised\twith\tthe\tuse\tof\tpharmacologic\tdoses.\tFor\texample,\talthough\tsome\tstudies\thave\tseen\tno
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negative\teffects\ton\tDNA\tmethylation\tat\tdoses\tup\tto\t4000\tmcg/day\t(\nCrider\tet\tal,\t2011\n),\tother\tstudies\nhave\tfound\tthat,\tin\tthe\tcontext\tof\tlow\tvitamin\tB\n12\n\tstatus,\tsupplementing\tpregnant\twomen\twith\tjust\n500\tmcg/day\twas\tassociated\twith\tan\tincreased\trisk\tof\tdiabetes\tamong\tthe\n\twomen\t(\nPaul\tand\tSelhub,\n2017
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women\t(\nPaul\tand\tSelhub,\n2017\n)\tand\tof\toffspring\tadiposity\tand\tinsulin\tresistance\tat\tage\t6\t(\nYajnik\tet\tal,\t2008\n).\nOn\tthe\tother\thand,\tadequate\tfolic\tacid\tin\tthe\tsecond\ttrimester\tmay\tdecrease\tinflammation,\tand\nfolate\tstatus\tis\tassociated\tinversely\twith\tthe\tseverity\tof\tbacterial\tvaginosis,\ta\tdocumented\trisk\tfactor\nfor\tpreterm\tdelivery\t(
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for\tpreterm\tdelivery\t(\nDunlop\tet\tal,\t2011\n).\tMurine\tstudies\thave\tfound\tthat\tthe\tnegative\n\teffect\tof\nmaternal\texposure\tto\tbisphenol-A\tis\teffectively\tneutralized\tby\tmaternal\tsupplementation\twith\tfolic\nacid,\tbetaine,\tand\tcholine\t(\nGuéant\tet\tal,\t2013\n).\tSupplementation\twith\tmethyl\tdonors,\tsuch\tas\tfolic
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acid,\talso\tmay\treduce\tthe\tharmful\teffects\tof\tfumonisin\t(a\tmycotoxin\tproduced\tby\t\nFusarium\n\tmolds\nthat\tgrow\ton\tagricultural\tcommodities,\tespecially\tcorn,\tthat\thas\tbeen\tassociated\twith\tincreased\n\trisk\nof\tNTDs)\tcontamination.\tSpermatozoid\tfolate\tdeficiency\tamong\tmen\texposed\tto\tdioxins\tmay\tincrease
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