Women First: Preconception Maternal Nutrition

Mortality Clinical Trial

— WF  

Official title:

Women First: Preconception Maternal Nutrition

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01883193
• Other study ID #: 12-1672
• Secondary ID: OPP1055867U10HD0
• Status: Completed
• Phase: N/A
• Start date: August 2013
• Est. completion date: March 30, 2019

Study information

• Verified date: July 2021
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multi-country three-arm, individually randomized, non-masked, controlled trial to ascertain the benefits of ensuring optimal maternal nutrition before conception and providing an evidence base for programmatic priority directed to minimizing the risk of malnutrition in all females of reproductive age.

Description:

The objective is to determine the benefits to the offspring of women in poor, food-insecure environments of commencing a daily comprehensive maternal nutrition supplement (with additional balanced calorie/protein supplement for underweight participants) ≥ 3 months prior to conception versus the benefits of commencing the same supplement at 12 weeks gestation and also to compare offspring outcomes with those of a control group which receives no supplement.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7374
• Est. completion date: March 30, 2019
• Est. primary completion date: March 30, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 35 Years

Eligibility

Inclusion Criteria:

• 16-35 years of age;
• expectation to have first or further pregnancy without intent to utilize contraception
• Hb >8 g/dL

Exclusion Criteria:

• Nulliparous women who do not agree to hospital delivery (equipped for caesarian section) or/and do not have ready access to such a facility.

Related Conditions & MeSH terms

• Failure to Thrive
• Growth Failure
• Malnutrition
• Maternal Malnutrition
• Morbidity
• Mortality
• Stunting

Intervention

Dietary Supplement:
• Comprehensive Maternal Nutrition Intervention
The nutrition intervention will be delivered before conception or at 12 weeks gestation and continued through delivery and compared with a control group. The supplement to be used is a multi-micronutrient (MMN) fortified lipid-based supplement composed of dried skimmed milk, soybean and peanut extract, sugar, maltodextrin stabilizers, and emulsifiers.

Locations

Country	Name	City	State
Congo, The Democratic Republic of the	Kinshasa School of Public Health	Kinshasa
Guatemala	INCAP	Guatemala City
India	Jawaharlal Nehru Medical College	Belgaum
Pakistan	Aga Khan University	Karachi

Sponsors (7)

Lead Sponsor	Collaborator
University of Colorado, Denver	Aga Khan University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Instituto de Nutricion de Centroamerica y Panama (INCAP), Jawaharlal Nehru Medical College, Kinshasa School of Public Health, RTI International

Countries where clinical trial is conducted

Congo, The Democratic Republic of the,  Guatemala,  India,  Pakistan, 

References & Publications (16)

Ali SA, Abbasi Z, Shahid B, Moin G, Hambidge KM, Krebs NF, Westcott JE, McClure EM, Goldenberg RL, Saleem S. Prevalence and determinants of anemia among women of reproductive age in Thatta Pakistan: Findings from a cross-sectional study. PLoS One. 2020 Sep 24;15(9):e0239320. doi: 10.1371/journal.pone.0239320. eCollection 2020. — View Citation

Ali SA, Khan U, Abrejo F, Saleem S, Hambidge MK, Krebs NF, Westcott JE, Goldenberg RL, McClure EM, Pasha O. Challenges of Implementing an Individual Randomized Controlled Trial (Women First: Preconception Maternal Nutrition Study) in a Rural Study Site: A Case Study From Pakistan. Nutr Metab Insights. 2019 Jul 4;21:1178638819852059. doi: 10.1177/1178638819852059. eCollection 2019. — View Citation

Aziz Ali S, Abbasi Z, Feroz A, Hambidge KM, Krebs NF, Westcott JE, Saleem S. Factors associated with anemia among women of the reproductive age group in Thatta district: study protocol. Reprod Health. 2019 Mar 18;16(1):34. doi: 10.1186/s12978-019-0688-7. — View Citation

Aziz Ali S, Khan U, Abrejo F, Vollmer B, Saleem S, Hambidge MK, Krebs NF, Westcott JE, Goldenberg RL, McClure EM, Pasha O. Use of smokeless tobacco before conception and its relationship with maternal and fetal outcomes of pregnancy in Thatta, Pakistan: Findings from Women First study. Nicotine Tob Res. 2020 Oct 21. pii: ntaa215. doi: 10.1093/ntr/ntaa215. [Epub ahead of print] — View Citation

Borengasser SJ, Baker PR 2nd, Kerns ME, Miller LV, Palacios AP, Kemp JF, Westcott JE, Morrison SD, Hernandez TL, Garces A, Figueroa L, Friedman JE, Hambidge KM, Krebs NF. Preconception Micronutrient Supplementation Reduced Circulating Branched Chain Amino Acids at 12 Weeks Gestation in an Open Trial of Guatemalan Women Who Are Overweight or Obese. Nutrients. 2018 Sep 11;10(9). pii: E1282. doi: 10.3390/nu10091282. — View Citation

Dhaded SM, Hambidge KM, Ali SA, Somannavar M, Saleem S, Pasha O, Khan U, Herekar V, Vernekar S, Kumar S Y, Westcott JE, Thorsten VR, Sridhar A, Das A, McClure E, Derman RJ, Goldenberg RL, Koso-Thomas M, Goudar SS, Krebs NF. Preconception nutrition intervention improved birth length and reduced stunting and wasting in newborns in South Asia: The Women First Randomized Controlled Trial. PLoS One. 2020 Jan 29;15(1):e0218960. doi: 10.1371/journal.pone.0218960. eCollection 2020. — View Citation

Gilley SP, Weaver NE, Sticca EL, Jambal P, Palacios A, Kerns ME, Anand P, Kemp JF, Westcott JE, Figueroa L, Garcés AL, Ali SA, Pasha O, Saleem S, Hambidge KM, Hendricks AE, Krebs NF, Borengasser SJ. Longitudinal Changes of One-Carbon Metabolites and Amino Acid Concentrations during Pregnancy in the Women First Maternal Nutrition Trial. Curr Dev Nutr. 2019 Nov 18;4(1):nzz132. doi: 10.1093/cdn/nzz132. eCollection 2020 Jan. — View Citation

Hambidge KM, Bann CM, McClure EM, Westcott JE, Garcés A, Figueroa L, Goudar SS, Dhaded SM, Pasha O, Ali SA, Derman RJ, Goldenberg RL, Koso-Thomas M, Somannavar MS, Herekar V, Khan U, Krebs NF. Maternal Characteristics Affect Fetal Growth Response in the Women First Preconception Nutrition Trial. Nutrients. 2019 Oct 21;11(10). pii: E2534. doi: 10.3390/nu11102534. — View Citation

Hambidge KM, Krebs NF, Garcés A, Westcott JE, Figueroa L, Goudar SS, Dhaded S, Pasha O, Aziz Ali S, Tshefu A, Lokangaka A, Thorsten VR, Das A, Stolka K, McClure EM, Lander RL, Bose CL, Derman RJ, Goldenberg RL, Bauserman M. Anthropometric indices for non-pregnant women of childbearing age differ widely among four low-middle income populations. BMC Public Health. 2017 Jul 24;18(1):45. doi: 10.1186/s12889-017-4509-z. Erratum in: BMC Public Health. 2017 Sep 22;17 (1):736. — View Citation

Hambidge KM, Krebs NF, Westcott JE, Garces A, Goudar SS, Kodkany BS, Pasha O, Tshefu A, Bose CL, Figueroa L, Goldenberg RL, Derman RJ, Friedman JE, Frank DN, McClure EM, Stolka K, Das A, Koso-Thomas M, Sundberg S; Preconception Trial Group. Preconception maternal nutrition: a multi-site randomized controlled trial. BMC Pregnancy Childbirth. 2014 Mar 20;14:111. doi: 10.1186/1471-2393-14-111. — View Citation

Hambidge KM, Westcott JE, Garcés A, Figueroa L, Goudar SS, Dhaded SM, Pasha O, Ali SA, Tshefu A, Lokangaka A, Derman RJ, Goldenberg RL, Bose CL, Bauserman M, Koso-Thomas M, Thorsten VR, Sridhar A, Stolka K, Das A, McClure EM, Krebs NF; Women First Preconception Trial Study Group. A multicountry randomized controlled trial of comprehensive maternal nutrition supplementation initiated before conception: the Women First trial. Am J Clin Nutr. 2019 Feb 1;109(2):457-469. doi: 10.1093/ajcn/nqy228. — View Citation

Krebs NF, Hambidge KM, Westcott JL, Garcés AL, Figueroa L, Tsefu AK, Lokangaka AL, Goudar SS, Dhaded SM, Saleem S, Ali SA, Bose CL, Derman RJ, Goldenberg RL, Thorsten VR, Sridhar A, Chowdhury D, Das A; Women First Preconception Maternal Nutrition Study Group. Growth from Birth Through Six Months for Infants of Mothers in the "Women First" Preconception Maternal Nutrition Trial. J Pediatr. 2021 Feb;229:199-206.e4. doi: 10.1016/j.jpeds.2020.09.032. Epub 2020 Sep 18. — View Citation

Krebs NF, Hambidge KM. Response to Editorial: Balancing the benefits of maternal nutritional interventions; time to put women first! Am J Clin Nutr. 2019 Aug 1;110(2):521-522. doi: 10.1093/ajcn/nqz077. — View Citation

Lander RL, Hambidge KM, Krebs NF, Westcott JE, Garces A, Figueroa L, Tejeda G, Lokangaka A, Diba TS, Somannavar MS, Honnayya R, Ali SA, Khan US, McClure EM, Thorsten VR, Stolka KB; Women First Preconception Nutrition Trial Group. Repeat 24-hour recalls and locally developed food composition databases: a feasible method to estimate dietary adequacy in a multi-site preconception maternal nutrition RCT. Food Nutr Res. 2017 Apr 11;61(1):1311185. doi: 10.1080/16546628.2017.1311185. eCollection 2017. — View Citation

Lander RL, Hambidge KM, Westcott JE, Tejeda G, Diba TS, Mastiholi SC, Khan US, Garcés A, Figueroa L, Tshefu A, Lokangaka A, Goudar SS, Somannavar MS, Ali SA, Saleem S, McClure EM, Krebs NF, Group OBOTWFPNT. Pregnant Women in Four Low-Middle Income Countries Have a High Prevalence of Inadequate Dietary Intakes That Are Improved by Dietary Diversity. Nutrients. 2019 Jul 10;11(7). pii: E1560. doi: 10.3390/nu11071560. — View Citation

Tang M, Frank DN, Tshefu A, Lokangaka A, Goudar SS, Dhaded SM, Somannavar MS, Hendricks AE, Ir D, Robertson CE, Kemp JF, Lander RL, Westcott JE, Hambidge KM, Krebs NF. Different Gut Microbial Profiles in Sub-Saharan African and South Asian Women of Childbearing Age Are Primarily Associated With Dietary Intakes. Front Microbiol. 2019 Aug 14;10:1848. doi: 10.3389/fmicb.2019.01848. eCollection 2019. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neonatal linear growth	Research assistants will obtain neonatal length measurement at <24 hours of age.	<24 hours of age
Secondary	Length-for-age Z-scores	Research assistants will obtain infant anthropometry measurements, which include length, head circumference, triceps skin folds, Mid Upper Arm Circumference (MUAC), and weight, at age 0.5, 1, 3, 6, 12, 18 and 24 months of age. Length-for-age Z-scores will be compared for offspring of mothers randomized to the three intervention arms.	age 0.5, 1, 3, 6, 12, 18 and 24 months postnatal
Secondary	Estimate fetal growth	Ultrasound measurements will be undertaken at 12 weeks gestation with the goals of confirming gestational age and estimating fetal growth.	12 weeks gestation
Secondary	Mean birth weight	As a dichotomous variable, the cutoff of 2500 g does not have the power of the continuum of birth length, but is included because of the long history of use in determining which newborns are severely underweight and this association with impaired neonatal and long-term prognosis. The design of this study will allow distinction between pre-term birth (PTB) and growth retardation of the term infant (mature IUGR).	at birth
Secondary	Incidence of low birth weight (LBW) infants	As a dichotomous variable, the cutoff of 2500 g does not have the power of the continuum of birth length, but is included because of the long history of use in determining which newborns are severely underweight and this association with impaired neonatal and long-term prognosis. The design of this study will allow distinction between pre-term birth (PTB) and growth retardation of the term infant (mature IUGR).	at birth
Secondary	Perinatal Mortality	The outcome is to determine, in poor food insecure communities if a daily comprehensive maternal nutrition supplement starting = 3 months preconception and continuing throughout pregnancy will reduce the incidence of offspring perinatal mortality (including still births), compared with that for offspring of mothers who commence the same supplement starting at 12-16 weeks gestation.	From 20 weeks gestation through 1 month of age
Secondary	Incidence of severe neonatal and infant infectious disease	Outcome measure is number of acute visits / admissions to health center/hospital for severe infectious disease. This secondary outcome will provide insight into the importance of maternal and fetal nutrition in the early prenatal development of host-defense mechanisms and, through comparison with the prenatal and control Arms, on the importance of maternal nutrition throughout pregnancy. It is further intended to collect minor morbidity data.	birth to 6 months of age
Secondary	Epigenome (Maternal)	To compare longitudinal changes between groups in the maternal epigenome (including blood, buccal swabs, and possibly other readily obtainable samples) at baseline, 12 weeks pregnancy (prior to initiation of LNS in Arm 2), 34 weeks pregnancy, and at 3 months postpartum. Also will collect placental, fetal and cord blood epigenome at delivery by group and infant epigenome at 3 months with fingerstick blood and buccal swabs.	baseline, 12 and 34 weeks gestation, delivery, and 3 months postpartum (maternal); 2 weeks and 3 months of age (infant)
Secondary	Epigenome (Infant)	To compare longitudinal changes between groups in the maternal epigenome (including blood, buccal swabs, and possibly other readily obtainable samples) at baseline, 12 weeks pregnancy (prior to initiation of LNS in Arm 2), 34 weeks pregnancy, and at 3 months postpartum. Also will collect placental, fetal and cord blood epigenome at delivery by group and infant epigenome at 3 months with fingerstick blood and buccal swabs.	2 weeks and 3 months of age
Secondary	Deep phenotyping of maternal metabolic and nutritional status	The outcome represents deep phenotyping by measuring in maternal tissues: hormones, metabolites, measures of inflammation, oxidant stress and immune function/status, and nutrient biomarkers as possible indices of fundamental metabolic alterations resulting from improved long-term maternal nutrition in food insecure populations. Longitudinal blood samples will be collected from maternal participants in Arms 1 and 2 at baseline, 12 weeks gestation (prior to initiation of LNS in Arm 2), 34 weeks gestation, delivery and 3 months postpartum. Samples will also be collected from participants in Arm 3 at 34 weeks gestation and at 3 months postpartum.	12 and 34 weeks gestation, delivery, and 3 months postpartum
Secondary	Microbiome (maternal)	Based on potential long-term effects on maternal nutritional and metabolic state from preconception intervention, we hypothesize that the gut microbiota will differ between the two intervention arms at the three proposed time points.	12 & 34 weeks gestation and delivery (maternal)
Secondary	Microbiome (infant)	Based on potential long-term effects on maternal nutritional and metabolic state from preconception intervention, we hypothesize that the gut microbiota will differ between the two intervention arms at the three proposed time points.	14 days and 3 months of age (infant)
Secondary	Composition of breast milk	We hypothesize that improved maternal nutrition at the time of greatest plasticity in early pregnancy will favorably influence maternal metabolic and nutritional status throughout pregnancy and thus potentially the composition of breast milk in terms of hormonal content, immune factors, cytokines, and gut growth factors.	14 days postpartum
Secondary	Neurodevelopment assessment	Offspring randomized to receive neurodevelopmental evaluation (BSID-III or InterNDA, 2:1 ratio) at 24 mo of age	24 mo age
Secondary	Gestational weight gain (GWG)	Describe GWG and its associations with fetal growth and birth outcomes within each country by baseline maternal nutritional status (BMI) and the receipt of nutrition interventions. Evaluate how GWG might mediate the effects of maternal nutrition interventions.	Enrollment to delivery