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Preconception Nutrition Interventions and Intrauterine Growth: Exploring Mechanism and Identifying High-Risk Groups.
Preconception Nutrition Interventions and Intrauterine Growth: Exploring Mechanism and Identifying High-Risk Groups.

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자료유형  
 학위논문
Control Number  
0017160444
International Standard Book Number  
9798381951257
Dewey Decimal Classification Number  
614
Main Entry-Personal Name  
Aziz, Sumera.
Publication, Distribution, etc. (Imprint  
[S.l.] : Columbia University., 2024
Publication, Distribution, etc. (Imprint  
Ann Arbor : ProQuest Dissertations & Theses, 2024
Physical Description  
183 p.
General Note  
Source: Dissertations Abstracts International, Volume: 85-09, Section: B.
General Note  
Advisor: Kuhn, Louise.
Dissertation Note  
Thesis (Ph.D.)--Columbia University, 2024.
Summary, Etc.  
요약Impaired intrauterine growth, inability of the fetus to achieve the required growth potential, contributes to a higher burden of neonatal morbidity and mortality. Intrauterine growth is an inferred process and small for gestational age is considered a rough estimate of impaired intrauterine growth that requires reliable gestational age data. Due to sparse data and measurement errors in gestational age, researchers rely on markers such as birth weight, birth length, and birth head circumference to infer fetal growth. While the etiology of impaired fetal growth is multifactorial, maternal anemia and undernutrition contribute substantially to impaired fetal growth and are prioritized in 2030 global nutrition goals by the World Health Assembly. Nutrition supplements such as lipid-based nutrient supplements, multiple micronutrients, and iron or folic acid during pregnancy are presumed to improve maternal anemia. But, the effect of the supplements during pregnancy on fetal growth appears to be small to negligible, which has shifted the researcher's focus to the pre-conception period. However, prior reviews on the preconception period have either synthesized the evidence from observational studies, or have explored outcomes such as congenital anomalies (e.g., neural tube defects), neurodevelopment disorders, or only birth weight. Hence the evidence from existing randomized controlled trials (RCTs) evaluating the effect of preconception nutrition supplements on maternal anemia and all markers of fetal growth including birth weight, birth length, and birth head circumference has not been systematically summarized and synthesized. We bridged this knowledge gap in the current dissertation (Aim 1). The Women First (WF) Preconception Nutrition Trial found that lipid-based nutrient supplementation started preconception or during pregnancy conferred greater benefits for birth weight and birth length among mothers who were anemic (Hemoglobin (Hb) 12 g/dL) than among mothers who were non-anemic (Hb ≥ 12 g/dL) pre-pregnancy. However, by dichotomizing women into anemic and non-anemic women, we may miss high-risk women with specific Hb levels who may obtain greater benefits for intrauterine growth associated with the supplements. Assessing the effect of preconception nutrient supplements across a range of pre-pregnancy Hb levels will help us identify women with specific Hb cut-offs who may have the greatest potential to respond to the supplements (Aim 2). Additionally, there are major gaps in understanding the mechanisms of how nutrient supplements, consumed either before or during pregnancy, improve intrauterine growth. A better understanding of the underlying mechanisms would allow for fine-tuning of nutrition interventions for greater efficacy. Here, we examined whether Hb during pregnancy could be a potential mechanism through which nutrition supplements improve intrauterine growth (Aim 3). For Aim 1, we undertook a systematic review and meta-analysis of the RCTs evaluating the effect of preconception nutrition supplements on maternal hemoglobin and markers of intrauterine growth including birth weight, birth length, birth head circumference, and small for gestational age. Additionally, we examined preterm birth as an important perinatal outcome. We searched electronic databases including PubMed, Web of Science, Embase, CINAHL, and Cochrane Central. We computed pooled mean differences and risk ratios (RR) with 95% confidence intervals (CIs) using random-effect models. We employed I2 and Cochran's Q test statistics to assess heterogeneity. We used the GRADE (grading of recommendations, assessment, development, and evaluations) tool to assess the quality of evidence. For Aim 2 and Aim 3, we leveraged the existing data from a large multi-country Women First (WF) Preconception Nutrition Trial conducted in Pakistan, India, Guatemala, and the Democratic Republic of Congo. Women in the WF trial were randomized to consume a lipid-based nutrient supplement (LNS) at least three months before and during pregnancy (Arm 1- preconception), only during pregnancy (Arm 2- during), or not at all (Arm 3 - control). The outcome was weight, length, and head circumference within 48 hours of birth expressed as Z-scores. For Aim 2, we analyzed the WF trial data on 2443 women-newborn dyads. For each site, we computed adjusted mean differences in these Z-scores between the randomized arms across six pre-pregnancy Hb categories (8-8.9, 9-9.9, 10-10.9, 11-11.9, 12-12.9, and ≥13g/dL) based on Hb distributions. We pooled site-specific effect measures using meta-analysis. For Aim 3, hemoglobin measured at 12 (n=2075) and 32 weeks of gestation (n=2157) was a mediator. We employed causal mediation analysis under a counterfactual approach to estimate direct and indirect effects. For Aim 1, we identified 20 eligible RCTs (n=27,659 women). Preconception nutrition supplements (iron and folic acid, multiple micronutrients, and a lipid-based nutrient supplement) increased maternal hemoglobin by 0.30g/dL ((0.03, 0.57); I2=79%). However, we did not find a significant effect of the supplements on birth weight (12.47gm ((-33.14, 58.08); I2=58%)), birth length (0.15cm (-0.26, 0.56); I2=68%; n=5), birth head circumference (-0.23cm (-0.88, 0.43); I2=84%), small for gestational age (RR: 0.91 (0.80,1.04); I2=31%), or preterm birth (RR: 0.93 (0.69,1.25); I2=57%). Overall, the quality of evidence was assessed as moderate and very low for maternal hemoglobin and three markers of intrauterine growth including birth weight, birth length, and birth head circumference, respectively. In Aim 2, we found that the effect of LNS on birth weight, length, and head circumference varied by pre-pregnancy Hb categories. Pooled mean differences in the Z-scores for birth length (0.60 (0.03, 1.23)), birth weight (0.50, (0.11, 0.89)), and birth head circumference ((0.26, (0.02, 0.51)) were greatest for Arm 1-preconception vs. Arm 3-control women with Hb 9-9.9g/dL. Women with Hb 10-10.9g/dL also benefited from preconception LNS. However, compared to controls, the effects of preconception LNS on birth weight, birth length, and birth head circumference attenuated for women with Hb 10-10.9g/dL. Compared to Arm 3-control, LNS during pregnancy (Arm 2) improved birth length, birth weight, and birth head circumference for women with Hb 8-10.9g/dL. Preconception LNS (Arm1) vs. LNS during pregnancy (Arm 2) improved the three markers of intrauterine growth only for women with Hb 9-9.9g/dL. Women with nearly normal (11-11.9 g/dL) and normal Hb (≥12g/dL) did not appreciably benefit from LNS, offered before and or during pregnancy.For Aim 3, Hb at 12 or 32 weeks of gestation did not mediate the relationship between the LNS and intrauterine growth. Indirect effects of preconception LNS (Arm 1) vs. Arm 3, mediated by Hb at 12 weeks, were 0.02 (-0.02, 0.01), 0.01 (-0.01, 0.02), and 0.01 (-0.01, 0.02) for length, weight, and head circumference Z-scores, respectively. The corresponding direct effects, not mediated by Hb, were 0.18 (0.09, 0.33), 0.12 (0.03, 0.23), and 0.06 (-0.03, 0.20), respectively. Site-specific and gestational age-adjusted data analyses both at 12 and 32 weeks of gestation confirmed the findings of negligible mediation by Hb during pregnancy. All types of preconception nutrition supplements studied to date appear to reduce maternal anemia. However, it is uncertain whether there are beneficial effects of preconception nutrition supplements on markers of intrauterine growth. Low quality of evidence from the RCTs examining the markers of intrauterine growth warrants future well-designed RCTs to produce solid scientific data, particularly on the benefits of a more comprehensive package of preconception nutrition supplements that include both macro- and micronutrients. The findings from the WF trial suggest that the benefits of preconception LNS on fetal growth are mainly confined to women with pre-pregnancy Hb 9-9.9g/dL. Compared to controls, women with Hb 10-10.9g/dL also benefited from preconception LNS, albeit the magnitude of effect on three markers of intrauterine growth was modest for women with Hb 10-10.9g/dL. However, LNS, started during pregnancy, appeared to improve markers of intrauterine growth for women with a wider range of Hb 8-10.9g/dL. Women with Hb ≥ 11g/dL did not benefit from LNS started either pre-conception or during pregnancy.
Summary, Etc.  
요약These findings suggest that prioritizing women with specific pre-pregnancy Hb categories for targeted nutrition interventions may be advisable. This would target limited resources most efficiently in LMICs. Lastly, negligible mediation by Hb during pregnancy suggests that alternative pathways that potentially mediate the relationship between LNS and intrauterine growth need to be investigated.
Subject Added Entry-Topical Term  
Public health.
Subject Added Entry-Topical Term  
Obstetrics.
Subject Added Entry-Topical Term  
Nutrition.
Index Term-Uncontrolled  
Causal mediation
Index Term-Uncontrolled  
Hemoglobin
Index Term-Uncontrolled  
High risk groups
Index Term-Uncontrolled  
Intrauterine growth
Index Term-Uncontrolled  
Preconception
Added Entry-Corporate Name  
Columbia University Epidemiology
Host Item Entry  
Dissertations Abstracts International. 85-09B.
Electronic Location and Access  
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Control Number  
joongbu:655114

MARC

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■1001  ▼aAziz,  Sumera.
■24510▼aPreconception  Nutrition  Interventions  and  Intrauterine  Growth:  Exploring  Mechanism  and  Identifying  High-Risk  Groups.
■260    ▼a[S.l.]▼bColumbia  University.  ▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a183  p.
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-09,  Section:  B.
■500    ▼aAdvisor:  Kuhn,  Louise.
■5021  ▼aThesis  (Ph.D.)--Columbia  University,  2024.
■520    ▼aImpaired  intrauterine  growth,  inability  of  the  fetus  to  achieve  the  required  growth  potential,  contributes  to  a  higher  burden  of  neonatal  morbidity  and  mortality.  Intrauterine  growth  is  an  inferred  process  and  small  for  gestational  age  is  considered  a  rough  estimate  of  impaired  intrauterine  growth  that  requires  reliable  gestational  age  data.  Due  to  sparse  data  and  measurement  errors  in  gestational  age,  researchers  rely  on  markers  such  as  birth  weight,  birth  length,  and  birth  head  circumference  to  infer  fetal  growth.  While  the  etiology  of  impaired  fetal  growth  is  multifactorial,  maternal  anemia  and  undernutrition  contribute  substantially  to  impaired  fetal  growth  and  are  prioritized  in  2030  global  nutrition  goals  by  the  World  Health  Assembly.  Nutrition  supplements  such  as  lipid-based  nutrient  supplements,  multiple  micronutrients,  and  iron  or  folic  acid  during  pregnancy  are  presumed  to  improve  maternal  anemia.  But,  the  effect  of  the  supplements  during  pregnancy  on  fetal  growth  appears  to  be  small  to  negligible,  which  has  shifted  the  researcher's  focus  to  the  pre-conception  period.  However,  prior  reviews  on  the  preconception  period  have  either  synthesized  the  evidence  from  observational  studies,  or  have  explored  outcomes  such  as  congenital  anomalies  (e.g.,  neural  tube  defects),  neurodevelopment  disorders,  or  only  birth  weight.  Hence  the  evidence  from  existing  randomized  controlled  trials  (RCTs)  evaluating  the  effect  of  preconception  nutrition  supplements  on  maternal  anemia  and  all  markers  of  fetal  growth  including  birth  weight,  birth  length,  and  birth  head  circumference  has  not  been  systematically  summarized  and  synthesized.  We  bridged  this  knowledge  gap  in  the  current  dissertation  (Aim  1).  The  Women  First  (WF)  Preconception  Nutrition  Trial  found  that  lipid-based  nutrient  supplementation  started  preconception  or  during  pregnancy  conferred  greater  benefits  for  birth  weight  and  birth  length  among  mothers  who  were  anemic  (Hemoglobin  (Hb)    12  g/dL)  than  among  mothers  who  were  non-anemic  (Hb  ≥  12  g/dL)  pre-pregnancy.  However,  by  dichotomizing  women  into  anemic  and  non-anemic  women,  we  may  miss  high-risk  women  with  specific  Hb  levels  who  may  obtain  greater  benefits  for  intrauterine  growth  associated  with  the  supplements.  Assessing  the  effect  of  preconception  nutrient  supplements  across  a  range  of  pre-pregnancy  Hb  levels  will  help  us  identify  women  with  specific  Hb  cut-offs  who  may  have  the  greatest  potential  to  respond  to  the  supplements  (Aim  2).  Additionally,  there  are  major  gaps  in  understanding  the  mechanisms  of  how  nutrient  supplements,  consumed  either  before  or  during  pregnancy,  improve  intrauterine  growth.  A  better  understanding  of  the  underlying  mechanisms  would  allow  for  fine-tuning  of  nutrition  interventions  for  greater  efficacy.  Here,  we  examined  whether  Hb  during  pregnancy  could  be  a  potential  mechanism  through  which  nutrition  supplements  improve  intrauterine  growth  (Aim  3).  For  Aim  1,  we  undertook  a  systematic  review  and  meta-analysis  of  the  RCTs  evaluating  the  effect  of  preconception  nutrition  supplements  on  maternal  hemoglobin  and  markers  of  intrauterine  growth  including  birth  weight,  birth  length,  birth  head  circumference,  and  small  for  gestational  age.  Additionally,  we  examined  preterm  birth  as  an  important  perinatal  outcome.  We  searched  electronic  databases  including  PubMed,  Web  of  Science,  Embase,  CINAHL,  and  Cochrane  Central.  We  computed  pooled  mean  differences  and  risk  ratios  (RR)  with  95%  confidence  intervals  (CIs)  using  random-effect  models.  We  employed  I2  and  Cochran's  Q  test  statistics  to  assess  heterogeneity.  We  used  the  GRADE  (grading  of  recommendations,  assessment,  development,  and  evaluations)  tool  to  assess  the  quality  of  evidence.  For  Aim  2  and  Aim  3,  we  leveraged  the  existing  data  from  a  large  multi-country  Women  First  (WF)  Preconception  Nutrition  Trial  conducted  in  Pakistan,  India,  Guatemala,  and  the  Democratic  Republic  of  Congo.  Women  in  the  WF  trial  were  randomized  to  consume  a  lipid-based  nutrient  supplement  (LNS)  at  least  three  months  before  and  during  pregnancy  (Arm  1-  preconception),  only  during  pregnancy  (Arm  2-  during),  or  not  at  all  (Arm  3  -  control).  The  outcome  was  weight,  length,  and  head  circumference  within  48  hours  of  birth  expressed  as  Z-scores.  For  Aim  2,  we  analyzed  the  WF  trial  data  on  2443  women-newborn  dyads.  For  each  site,  we  computed  adjusted  mean  differences  in  these  Z-scores  between  the  randomized  arms  across  six  pre-pregnancy  Hb  categories  (8-8.9,  9-9.9,  10-10.9,  11-11.9,  12-12.9,  and  ≥13g/dL)  based  on  Hb  distributions.  We  pooled  site-specific  effect  measures  using  meta-analysis.  For  Aim  3,  hemoglobin  measured  at  12  (n=2075)  and  32  weeks  of  gestation  (n=2157)  was  a  mediator.  We  employed  causal  mediation  analysis  under  a  counterfactual  approach  to  estimate  direct  and  indirect  effects.  For  Aim  1,  we  identified  20  eligible  RCTs  (n=27,659  women).  Preconception  nutrition  supplements  (iron  and  folic  acid,  multiple  micronutrients,  and  a  lipid-based  nutrient  supplement)  increased  maternal  hemoglobin  by  0.30g/dL  ((0.03,  0.57);  I2=79%).  However,  we  did  not  find  a  significant  effect  of  the  supplements  on  birth  weight  (12.47gm  ((-33.14,  58.08);  I2=58%)),  birth  length  (0.15cm  (-0.26,  0.56);  I2=68%;  n=5),  birth  head  circumference  (-0.23cm  (-0.88,  0.43);  I2=84%),  small  for  gestational  age  (RR:  0.91  (0.80,1.04);  I2=31%),  or  preterm  birth  (RR:  0.93  (0.69,1.25);  I2=57%).  Overall,  the  quality  of  evidence  was  assessed  as  moderate  and  very  low  for  maternal  hemoglobin  and  three  markers  of  intrauterine  growth  including  birth  weight,  birth  length,  and  birth  head  circumference,  respectively.  In  Aim  2,  we  found  that  the  effect  of  LNS  on  birth  weight,  length,  and  head  circumference  varied  by  pre-pregnancy  Hb  categories.  Pooled  mean  differences  in  the  Z-scores  for  birth  length  (0.60  (0.03,  1.23)),  birth  weight  (0.50,  (0.11,  0.89)),  and  birth  head  circumference  ((0.26,  (0.02,  0.51))  were  greatest  for  Arm  1-preconception  vs.  Arm  3-control  women  with  Hb  9-9.9g/dL.  Women  with  Hb  10-10.9g/dL  also  benefited  from  preconception  LNS.  However,  compared  to  controls,  the  effects  of  preconception  LNS  on  birth  weight,  birth  length,  and  birth  head  circumference  attenuated  for  women  with  Hb  10-10.9g/dL.  Compared  to  Arm  3-control,  LNS  during  pregnancy  (Arm  2)  improved  birth  length,  birth  weight,  and  birth  head  circumference  for  women  with  Hb  8-10.9g/dL.  Preconception  LNS  (Arm1)  vs.  LNS  during  pregnancy  (Arm  2)  improved  the  three  markers  of  intrauterine  growth  only  for  women  with  Hb  9-9.9g/dL.  Women  with  nearly  normal  (11-11.9  g/dL)  and  normal  Hb  (≥12g/dL)  did  not  appreciably  benefit  from  LNS,  offered  before  and  or  during  pregnancy.For  Aim  3,  Hb  at  12  or  32  weeks  of  gestation  did  not  mediate  the  relationship  between  the  LNS  and  intrauterine  growth.  Indirect  effects  of  preconception  LNS  (Arm  1)  vs.  Arm  3,  mediated  by  Hb  at  12  weeks,  were  0.02  (-0.02,  0.01),  0.01  (-0.01,  0.02),  and  0.01  (-0.01,  0.02)  for  length,  weight,  and  head  circumference  Z-scores,  respectively.  The  corresponding  direct  effects,  not  mediated  by  Hb,  were  0.18  (0.09,  0.33),  0.12  (0.03,  0.23),  and  0.06  (-0.03,  0.20),  respectively.  Site-specific  and  gestational  age-adjusted  data  analyses  both  at  12  and  32  weeks  of  gestation  confirmed  the  findings  of  negligible  mediation  by  Hb  during  pregnancy.  All  types  of  preconception  nutrition  supplements  studied  to  date  appear  to  reduce  maternal  anemia.  However,  it  is  uncertain  whether  there  are  beneficial  effects  of  preconception  nutrition  supplements  on  markers  of  intrauterine  growth.  Low  quality  of  evidence  from  the  RCTs  examining  the  markers  of  intrauterine  growth  warrants  future  well-designed  RCTs  to  produce  solid  scientific  data,  particularly  on  the  benefits  of  a  more  comprehensive  package  of  preconception  nutrition  supplements  that  include  both  macro-  and  micronutrients.  The  findings  from  the  WF  trial  suggest  that  the  benefits  of  preconception  LNS  on  fetal  growth  are  mainly  confined  to  women  with  pre-pregnancy  Hb  9-9.9g/dL.  Compared  to  controls,  women  with  Hb  10-10.9g/dL  also  benefited  from  preconception  LNS,  albeit  the  magnitude  of  effect  on  three  markers  of  intrauterine  growth  was  modest  for  women  with  Hb  10-10.9g/dL.  However,  LNS,  started  during  pregnancy,  appeared  to  improve  markers  of  intrauterine  growth  for  women  with  a  wider  range  of  Hb  8-10.9g/dL.  Women  with  Hb  ≥  11g/dL  did  not  benefit  from  LNS  started  either  pre-conception  or  during  pregnancy.  
■520    ▼aThese  findings  suggest  that  prioritizing  women  with  specific  pre-pregnancy  Hb  categories  for  targeted  nutrition  interventions  may  be  advisable.  This  would  target  limited  resources  most  efficiently  in  LMICs.  Lastly,  negligible  mediation  by  Hb  during  pregnancy  suggests  that  alternative  pathways  that  potentially  mediate  the  relationship  between  LNS  and  intrauterine  growth  need  to  be  investigated.
■590    ▼aSchool  code:  0054.
■650  4▼aPublic  health.
■650  4▼aObstetrics.
■650  4▼aNutrition.
■653    ▼aCausal  mediation
■653    ▼aHemoglobin
■653    ▼aHigh  risk  groups
■653    ▼aIntrauterine  growth
■653    ▼aPreconception
■690    ▼a0573
■690    ▼a0380
■690    ▼a0570
■71020▼aColumbia  University▼bEpidemiology.
■7730  ▼tDissertations  Abstracts  International▼g85-09B.
■790    ▼a0054
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160444▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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