PMID- 33382407
OWN - NLM
STAT- MEDLINE
DCOM- 20210512
LR  - 20240207
IS  - 1541-6100 (Electronic)
IS  - 0022-3166 (Print)
IS  - 0022-3166 (Linking)
VI  - 151
IP  - 3
DP  - 2021 Mar 11
TI  - Preconceptional Lipid-Based Nutrient Supplementation in 2 Low-Resource Countries 
      Results in Distinctly Different IGF-1/mTOR Placental Responses.
PG  - 556-569
LID - 10.1093/jn/nxaa354 [doi]
AB  - BACKGROUND: Preconceptional maternal small-quantity lipid-based nutrient 
      supplementation (SQLNS) improved intrauterine linear growth in low-resource 
      countries as demonstrated by the Women First Preconception Maternal Nutrition 
      Trial (WF). Fetal growth is dependent on nutrient availability and regulated by 
      insulin-like growth factor 1 (IGF-1) through changes in placental transfer 
      capacity, mediated by the mechanistic target of rapamycin (mTOR) pathway. 
      OBJECTIVES: Our objective was to evaluate the role of placental mTOR and IGF-1 
      signaling on fetal growth in women from 2 low-resource countries with high rates 
      of stunting after they received preconceptional SQLNS. METHODS: We studied 48 
      women from preconception through delivery who were from Guatemala and Pakistan 
      and received SQLNS or not, as part of the WF study. Placental samples were 
      obtained at delivery (control, n = 24; SQLNS, n = 24). Placental protein or mRNA 
      expression of eukaryotic translation initiation factor binding protein-1 
      (4E-BP1), ribosomal protein S6 (rpS6), AMP-activated protein kinase alpha (AMPKA), 
      IGF-1, insulin-like growth factor receptor (IGF-1R), and pregnancy associated 
      plasma protein (PAPP)-A, and DNA methylation of the IGF1 promoter were 
      determined. Maternal serum IGF-1, insulin-like growth factor binding protein 
      (IGFBP)-3, IGFBP-4, IGFBP-5, PAPP-A, PAPP-A2, and zinc were measured. RESULTS: 
      Mean +/- SEM maternal prepregnancy BMI differed between participants in Guatemala 
      (26.5 +/- 1.3) and Pakistan (19.8 +/- 0.7) (P < 0.001). In Pakistani participants, 
      SQLNS increased the placental rpS6(T37/46):rpS6 ratio (1.5-fold) and decreased 
      the AMPKA(T172):AMPKA ratio. Placental IGF1 mRNA expression was positively 
      correlated with birth length and birth weight z-scores. Placental PAPP-A 
      (30-fold) and maternal serum zinc (1.2-fold) increased with SQLNS. In Guatemalan 
      participants SQLNS did not influence placental mTOR signaling. Placental IGF-1R 
      protein expression was positively associated with birth length and birth weight 
      z-scores. SQLNS increased placental PAPP-A (40-fold) and maternal serum IGFBP-4 
      (1.6-fold). CONCLUSIONS: In Pakistani pregnant women with poor nutritional 
      status, preconceptional SQLNS activated placental mTOR and IGF-1 signaling and 
      was associated with improved fetal growth. In contrast, in Guatemalan women SQLNS 
      did not activate placental nutrient-sensing pathways. In populations experiencing 
      childhood stunting, preconceptional SQLNS improves placental function and fetal 
      growth only in the context of poor maternal nutrition. This trial was registered 
      at clinicaltrials.gov as NCT01883193.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      American Society for Nutrition.
FAU - Castillo-Castrejon, Marisol
AU  - Castillo-Castrejon M
AD  - Division of Reproductive Sciences, Department of Obstetrics and Gynecology, 
      University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
FAU - Yang, Ivana V
AU  - Yang IV
AD  - Biomedical Informatics & Personalized Medicine, Department of Medicine, 
      University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
FAU - Davidson, Elizabeth J
AU  - Davidson EJ
AD  - Biomedical Informatics & Personalized Medicine, Department of Medicine, 
      University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
FAU - Borengasser, Sarah J
AU  - Borengasser SJ
AD  - Section of Nutrition, Department of Pediatrics, University of Colorado Anschutz 
      Medical Campus, Aurora, CO, USA.
FAU - Jambal, Purevsuren
AU  - Jambal P
AD  - Section of Nutrition, Department of Pediatrics, University of Colorado Anschutz 
      Medical Campus, Aurora, CO, USA.
FAU - Westcott, Jamie
AU  - Westcott J
AD  - Section of Nutrition, Department of Pediatrics, University of Colorado Anschutz 
      Medical Campus, Aurora, CO, USA.
FAU - Kemp, Jennifer F
AU  - Kemp JF
AD  - Section of Nutrition, Department of Pediatrics, University of Colorado Anschutz 
      Medical Campus, Aurora, CO, USA.
FAU - Garces, Ana
AU  - Garces A
AD  - Maternal and Infant Health Center, Institute of Nutrition of Central America and 
      Panama (INCAP), Guatemala City, Guatemala.
FAU - Ali, Sumera A
AU  - Ali SA
AD  - Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan.
FAU - Saleem, Sarah
AU  - Saleem S
AD  - Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan.
FAU - Goldenberg, Robert L
AU  - Goldenberg RL
AD  - Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA.
FAU - Figueroa, Lester
AU  - Figueroa L
AD  - Maternal and Infant Health Center, Institute of Nutrition of Central America and 
      Panama (INCAP), Guatemala City, Guatemala.
FAU - Hambidge, K Michael
AU  - Hambidge KM
AD  - Section of Nutrition, Department of Pediatrics, University of Colorado Anschutz 
      Medical Campus, Aurora, CO, USA.
FAU - Krebs, Nancy F
AU  - Krebs NF
AD  - Section of Nutrition, Department of Pediatrics, University of Colorado Anschutz 
      Medical Campus, Aurora, CO, USA.
FAU - Powell, Theresa L
AU  - Powell TL
AD  - Section of Neonatology, Department of Pediatrics, University of Colorado Anschutz 
      Medical Campus, Aurora, CO, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01883193
GR  - K01 DK109077/DK/NIDDK NIH HHS/United States
GR  - P30 DK048520/DK/NIDDK NIH HHS/United States
GR  - R01 HD068370/HD/NICHD NIH HHS/United States
GR  - UG1 HD078438/HD/NICHD NIH HHS/United States
GR  - UG1 HD076474/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 0 (Lipids)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - J Nutr. 2021 Mar 11;151(3):471-472. PMID: 33561208
MH  - Developing Countries
MH  - *Dietary Supplements
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Insulin-Like Growth Factor I/genetics/*metabolism
MH  - Lipids/*chemistry
MH  - Placenta/drug effects/*metabolism
MH  - *Preconception Care
MH  - Pregnancy
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC7948206
OTO - NOTNLM
OT  - maternal-fetal exchange
OT  - nutrition
OT  - pregnancy
OT  - stunting
OT  - zinc
EDAT- 2021/01/01 06:00
MHDA- 2021/05/13 06:00
PMCR- 2020/12/31
CRDT- 2020/12/31 12:07
PHST- 2019/12/20 00:00 [received]
PHST- 2020/04/27 00:00 [revised]
PHST- 2020/10/14 00:00 [accepted]
PHST- 2021/01/01 06:00 [pubmed]
PHST- 2021/05/13 06:00 [medline]
PHST- 2020/12/31 12:07 [entrez]
PHST- 2020/12/31 00:00 [pmc-release]
AID - S0022-3166(22)00064-5 [pii]
AID - nxaa354 [pii]
AID - 10.1093/jn/nxaa354 [doi]
PST - ppublish
SO  - J Nutr. 2021 Mar 11;151(3):556-569. doi: 10.1093/jn/nxaa354.