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The Journal of Maternal-Fetal & Neonatal Medicine

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Impact of maternal nutritional supplementation inconjunction with a breastfeeding support programon breastfeeding performance, birth, and growthoutcomes in a Vietnamese population

Dieu T. T. Huynh, Nga T. Tran, Lam T. Nguyen, Yatin Berde & Yen Ling Low

To cite this article: Dieu T. T. Huynh, Nga T. Tran, Lam T. Nguyen, Yatin Berde & Yen LingLow (2018) Impact of maternal nutritional supplementation in conjunction with a breastfeedingsupport program on breastfeeding performance, birth, and growth outcomes in a Vietnamesepopulation, The Journal of Maternal-Fetal & Neonatal Medicine, 31:12, 1586-1594, DOI:10.1080/14767058.2017.1320984

To link to this article: https://doi.org/10.1080/14767058.2017.1320984

© 2017 The Author(s). Published by InformaUK Limited, trading as Taylor & FrancisGroup

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ORIGINAL ARTICLE

Impact of maternal nutritional supplementation in conjunction with abreastfeeding support program on breastfeeding performance, birth, andgrowth outcomes in a Vietnamese population

Dieu T. T. Huynha, Nga T. Tranb, Lam T. Nguyenb, Yatin Berdec and Yen Ling Lowa

aAbbott Nutrition Research and Development Asia-Pacific Center, Singapore; bNational Institution of Nutrition, Ha Noi, Vietnam;cStatistical Services, Cognizant Technologies Solution Pvt. Ltd., Hiranandani Business Park, Mumbai, India

ABSTRACTPurpose: This study aimed to evaluate the effects of maternal nutritional supplementation(MNS) in conjunction with a breastfeeding support program on birth outcomes and breastfeed-ing performance.Methods: A total of 228 singleton Vietnamese mothers aged 20–35 years at 26–29weeks of ges-tation with pre-pregnancy body mass index (BMI)< 25.0 kg/m2 were randomized to the interven-tion (n¼ 114), receiving MNS (252 kcal/day) daily up to 12weeks postpartum and fourbreastfeeding education and support sessions or to the control (n¼ 114), receiving standards ofcare.Results: The intervention was 2.09 times more likely to exclusively breastfeed over the 12weeksthan the control (95%CI: 1.05–4.13, p¼ .0358), after controlling for potential confounders. Infant’sbreast milk intake was significantly higher in the intervention than the control among motherswith baseline mid-upper arm circumference (MUAC)< 50th (p¼ .0251). Infants in the interventionhad significantly higher birth weight (p¼ .0312), birth weight-for-age (p¼ .0141) and birth headcircumference-for-age (p¼ .0487), and higher head circumference-for-age z-score (p¼ .0183)development over the postnatal period, compared with the control.Conclusions: Use of MNS and breastfeeding support improve birth outcomes and exclusivebreastfeeding (EBF) rate in Vietnamese mothers. Additionally, it promotes breast milk productionamong mothers with lower baseline MUAC.

ARTICLE HISTORYReceived 21 November 2016Revised 16 April 2017Accepted 17 April 2017

KEYWORDSMaternal nutritionalsupplementation; breast-feeding support; birthoutcomes; exclusivebreastfeeding; breast milkintake

Introduction

Recent evidence has demonstrated that maternalnutritional status plays an important role in birth out-comes and infant growth, especially during the “first1000 days window” from conception until 2 years ofage [1–3]. However, the prevalence of suboptimalmaternal nutritional status remains high, particularly inlow- and middle-income countries, due to low-nutrientdensity of the diets coupled with raised nutrientrequirements during pregnancy and breastfeeding[4–6]. Strategies aimed to improve maternal nutritionalstatus during both pre-natal (pregnancy) and post-natal (breastfeeding) periods have the potential toimprove maternal and child health [5–7].

Numerous studies have consistently demonstratedthat maternal nutritional supplementation (MNS) suchas multiple micronutrient or protein-energy supplement

during pre-natal period significantly increased birthweight and reduced the risk of low birthweight, com-pared to the control group, and this effect appeared tobe more pronounced among women who were under-nourished during pregnancy and those living in low-and medium-income countries [3,8–11]. The raisedmaternal nutritional requirements during pregnancyalso play an important role in building nutrient stores tosupport the mother for subsequent breastfeeding whichis a highly nutritionally demanding task [4,12–14].Hence, MNS during pregnancy may help the motherbetter accommodate the demands of breastfeeding.Further to this, MNS provided during post-natal periodmay further enhance maternal milk production [15–17].

While MNS during pre-natal period has beenstudied extensively, only a relatively small number ofstudies have been specifically designed to examine

CONTACT Dieu Huynh dieu.huynh@abbott.com Abbott Nutrition Research and Development, Asia-Pacific Center, 20 Biopolis Way, Unit 09-01/02Centros Building, Singapore

Supplemental data for this article can be accessed here.

� 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis GroupThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unre-stricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE, 2018VOL. 31, NO. 12, 1586–1594https://doi.org/10.1080/14767058.2017.1320984

the effects of MNS during postnatal period on mater-nal and child health in low-income countries. No studyto date has investigated the effects of MNS duringpre-natal period and continued through to post-natalperiod on exclusive breastfeeding (EBF) rate, birth out-comes, and infant growth. Previous research has high-lighted the importance of appropriate nutrition duringthe “first 1000 days window” for both short-term andlong-term health benefits of the offspring. Maternalnutrition during pre- and postnatal periods representsa continuum of nutrition provision for the breastfedoffspring during this critical 1000 days window. Goodmaternal nutrition prepares the mother to meet thehigh-nutritional demands of breastfeeding but themother will still need to learn the techniques ofbreastfeeding in order to breastfeed successfully. Wehypothesized that an improved perinatal nutrition careregimen comprising daily MNS supplementationstarted during pregnancy and continued through tolactation, bundled together with breastfeeding educa-tion, will significantly improve breastfeeding success,offspring growth outcome at birth and postnatallycompared to current standards of care.

The impact of such an improved perinatal nutritioncare regimen is likely to be greater in developingcountries where perinatal maternal nutrition care andmaternal nutritional status remains suboptimal, suchas in Vietnam [18–20]. Thus, we conducted this studyto determine the effects of an improved perinatalnutrition care regimen consisting of a daily MNS start-ing from the last trimester until 12weeks postpartumin combination with a breastfeeding support programon EBF rate, birth, and growth outcomes of the off-spring, compared with the controls receiving standardsof care in Vietnamese women.

Methods

Study design and participants

This was a prospective, randomized, open-label, paral-lel-group, multicenter study. It was conducted in 20commune medical stations and district hospitals acrossfour Northern provinces in Vietnam including HaiPhong, Ha Nam, Ninh Binh, and Thai Nguyen betweenOctober 2013 and April 2015.

Healthy pregnant women aged between 20 and35 years, first-time mother with a singleton pregnancyfrom 26 to 29weeks of gestation and pre-pregnancyBMI<25.0 kg/m2 were eligible for the study. Exclusioncriteria were smokers, known to be allergic or intoler-ant to any ingredient in the supplement, hadknown gestational diabetes and/or a diagnosis of

pre-eclampsia, or adverse maternal or fetal conditionsthat could have potential effects on child’s growthand/or development. Women and their infants werealso discontinued from the study if the infant was pre-term defined as gestational age <37weeks, had abirth weight <2500 g, or had conditions for the moth-ers or infants after delivery, which required intensivecare admission �24 h. For more details, please refer tothe Study Inclusion and Exclusion Criteria section(Supplemental Table 1).

The present study was approved by theIndependent Ethics Committees of the NationalInstitution of Nutrition and the Ministry of Health inVietnam. Informed written consent was obtained fromeach mother and her infant. The study was performedin accordance with the ethical principles that hadtheir origin in the Declaration of Helsinki. The trial wasregistered at clinicaltrials.gov, registration codeNCT02016586.

Intervention and control

Eligible women (n¼ 228) were randomized to receiveeither standard of care (control, n¼ 114) or MNS andbreastfeeding support (intervention, n¼ 114). For eachstudy site, sealed envelopes containing the studygroup assignment were prepared for both mother andher infant. Randomization schedules were computer-generated using a pseudo-random permuted blocksalgorithm. According to the local standards of care,women in the control group continued to take folicacid (400mcg) and iron (60mg) supplement untildelivery and received breastfeeding advice during pre-natal visits only if this was part of standard of care atthe sites. Breastfeeding advice consisting of messageson the benefits of breastfeeding and the encourage-ment of EBF during the first 6months was conductedby health care staff or health workers. Breastfeedingpromotion as a part of standard of care was also pro-vided through social media such as radio and televi-sion. Although the 10 steps of Baby-Friendly HospitalInitiative by WHO were not fully implemented acrossparticipating sites, practicing rooming in, encouragingmothers to breastfeed within a half an hour of birthand breastfeed on demand are common in these set-tings. The intervention group received two servings ofMNS daily starting from the last trimester until12weeks postpartum, and breastfeeding support con-sists of one prenatal breastfeeding class, one breast-feeding consultant visit within 48-h of delivery, onetelephone call at one week postpartum, and one face-to-face follow-up session at week 4 postpartum.Details of the content for each breastfeeding

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education and consultation session are included inSupplemental Table 2. The MNS was a commerciallyavailable powder product (Similac Mum; AbbottLaboratories, Vietnam) which was packaged in a 900 gtin and labeled as clinical study product for use in thestudy. Two daily servings of MNS provide 252 kcal, 16.8 g of protein, 1.4 g of fat, 39.2 g of carbohydrate, anda variety of micronutrients (Supplemental Table 3).

Study outcomes

The primary outcome was EBF rate at week 12 post-partum. Other outcomes include infant’s breast milkintake, breast milk energy content, the infant’s weight,length and head circumference (HC), the mother’senergy, macronutrient and micronutrient intakes,the mother’s body weight, BMI, and mid-upper armcircumference (MUAC).

Breastfeeding exclusivity

Mothers recorded the infant’s intake of breast milkand non-breast milk including formula, juice, water,and complementary foods on a daily basis. The intakeinformation was used to assess daily EBF from birth.WHO’s definition of EBF “receiving breast milk as theonly source of nutrition (including milk expressed orfrom a wet nurse), with no other liquids or solidsexcept for oral rehydration solution, vitamin drops,minerals, and medicines” is used to assess breastfeed-ing exclusivity [21].

Anthropometry

Maternal and infant anthropometric measurementswere performed by research staff of the NationalInstitution of Nutrition (NIN), Vietnam who was trainedon standardized methods for collecting the measure-ments. Maternal weight and MUAC were measured atbaseline, within 48-h of delivery and weeks 4, 8, and 12postpartum. Maternal height was measured only atenrollment. MUAC measured at baseline was used toassess the mother’s nutritional status during pregnancy.

Infant’s weight, length, and HC at birth were col-lected from medical records. Subsequent measure-ments at weeks 4, 8, and 12 were conducted by theresearch staff. Weight-for-age, HC-for-age, and length-for-age were expressed as sex-age-specific z-scoresusing the WHO Child Growth Standards [22]. Small forgestational age (SGA) was defined as birth weight(BW) or birth length (BL), which was at least 2 stand-ard deviations (SD) below the mean for the infant’sgestational age [23]. The detailed maternal and infant

anthropometric data collection is presented inSupplemental Table 4.

Breast milk intake and breast milk energy

Breast milk intake was measured in the mother’s homeat weeks 4, 8, and 12 postpartum using a standard 24-htest weighing procedure as previously described [24].The total number of breastfeeding sessions and the dur-ation of each breastfeeding session during each 24-htest weighing were recorded. Total milk intake was cal-culated by the sum of the differences in the infant’sweight before and after each nursing episode duringthe 24-h period. Breast milk samples for macronutrientanalyses were collected between 8 am and 12 pm atweeks 4, 8, and 12 according to a standardized samplingprotocol. Details of the test weighing procedures andbreast milk sampling, transportation, storage, and ana-lytical methods are presented in Supplemental Table 5.

Dietary intake and nutritional adequacy

Dietary intake was assessed at baseline and at weeks4, 8, and 12 postpartum by trained research staff fromNIN using a standardized 24-h food recall method-ology. Mothers were asked to recall food and bever-ages including the supplements she consumed in theprevious 24 h. Nutrient composition of the food recallswere analyzed using Vietnam Food CompositionTables. As the estimated average requirement (EAR) isonly available for a number of nutrients forVietnamese, the alternative method for assessing nutri-ent adequacy in this study is to use 77% of the 2016recommended daily allowance as a cutoff value [25].

Socio-demographic factors

Socio-demographic factors collected included maternalage and education level, economic status by owner-ship of assets from an inventory of household itemssuch as vehicles, entertainment appliances, and house-hold appliances. An index was constructed using anestablished principal component analysis method [26]to weigh the contribution of each asset to the index.

Information on delivery mode (natural, C-section),gestational age (weeks), and infant’s gender was col-lected from the medical records.

Statistical methods

Sample size

The sample size was calculated based on EBF rates at6months. A systematic review showed a 14.5% higher

1588 D. T. T. HUYNH ET AL.

6-month EBF rate in the intervention group receivingpre- and post-natal breastfeeding support comparedto the control group receiving standard of carerespectively [8]. In addition, a randomized controlledtrial reported a 10% higher EBF rate at week 20 post-partum in the high-energy supplement group com-pared to the low-energy supplement group [16].Therefore, it was estimated that a sample size of 228mothers (114 per group) would be required to detecta difference of 24.5% (14.5% plus 10%) in EBF ratesbetween groups using a two-tail test a of 5% with80% power assuming a 50% attrition rate (SASVR

Version 9.2, SAS Institute, Cary, NC).

Statistical analysis

All the statistical analyses were performed on theintent to treat (ITT) data set using SAS, version 9.3.Descriptive data including anthropometric measure-ments, infant’s breast milk intake, and breast milkenergy content were summarized by means and SDs.All continuous variables were checked for normalityusing combination methods including stem-and-leafplot of residuals, normality plot, and Shapiro–Wilk testand declared non-normal if found significant (p< .001).The nonparametric Wilcoxon test was used to examinethe differences between the two groups for continu-ous variable with non-normal distribution. Chi-squaretest was used to compare all categorical variablesbetween groups. p values<.0500 is considered statis-tically significant and .0500� p values� .1000 is con-sidered a trend.

The impact of the intervention on the probability ofEBF, the 24-h breast milk intake at weeks 4, 8, and 12,

infant’s weight, height, and HC from birth to week 12postpartum, maternal weight, and BMI from baselineto week 12 postpartum was examined using general-ized estimating equations (GEE) with an independentcorrelation structure, controlling for potential con-founders. In addition, analysis of covariance (ANCOVA)was used to assess the impact of the intervention onbirth outcomes, controlling for confounders. Withrespect to maternal macronutrient intakes over time,the repeated measures analysis of variance (ANOVA)was used, after conducting the log-transformation toimprove their normality. Details of factors, covariates,and modeling process GEE and ANCOVA analyses areprovided in Supplemental Table 6.

In addition, a post hoc analysis was performed todetermine whether the effect of the intervention oninfant’s breast milk intake differed between motherswith baseline MUAC below the median (<24.1 cm) ver-sus those with baseline MUAC equal to or above themedian (�24.1 cm).

Results

A total of 228 women from 26–29weeks gestationwere randomized to either the intervention group(n¼ 114) or the control group (n¼ 114), of whom 113women in each study group received their assignedtreatment group and were included in the ITT popula-tion. Nine subjects (7.9%) in the intervention and 13subjects (11.4%) in the control discontinued from thestudy (Figure 1). The characteristics of noncompleterswere not significantly different from completers ineach study group with regards to nutritional statusand socio-demographic factors (data not shown).

Screened and randomized n=228

Allocated to Intervention (n=114) Allocated to Control (n=114)

104 mother-infant pairs completed 100 mother-infant pairs completed

Intent to treat analysis (n=113)

1 exited the study before receiving study product

1 exited due to erroneous randomization

Intent to treat analysis (n=113)

Not completed (n=9) 5 did not meet eligibility criteria after delivery 2 exited due to AE 2 withdrew consent

Not completed (n=13) 10 did not meet eligibility criteria after delivery

1 exited due to SAE 2 loss of follow-up

Figure 1. Study flow chart.

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Socio-demographic characteristics, maternal nutri-tional status, and delivery mode were comparablebetween groups (Table 1). At birth, infants in the inter-vention group were significantly heavier than those inthe control group (p¼ .0346). There were no differen-ces between groups in BL and HC (p¼ .5195 andp¼ .1204, respectively).

Exclusive breastfeeding rate

The EBF rate in the intervention group was sustainedthroughout the 12-week postpartum while the controlgroup showed a decline over time (Figure 2). Theintervention was 2.09 (95%CI: 1.06, 4.13, p¼ .0358)times more likely to exclusively breastfeed than thecontrol over 12weeks postpartum, after controlling forpotential confounders.

Infant’s breast milk intake

There was no significant difference in infant’s breastmilk intake over 12weeks postpartum between theintervention group (n¼ 104) and control group(n¼ 100) (p¼ .3258) (data not shown). However, in aposthoc analysis, among mothers with baselineMUAC<50th percentile (24.1 cm), infants in the inter-vention group (n¼ 54) consumed 64.2 g more breastmilk than the control group (n¼ 47) over 12weekspostpartum (p¼ .0251), after controlling for confound-ers (Table 2). There were no differences betweengroups in the number of breastfeeding episodes andthe nursing duration over the 24-h test weighingperiod at three collection time points (p> .05), exceptfor a significantly shorter nursing duration at 8weekpostpartum in the intervention group compared tothe control group (p¼ .0115) (Supplemental Table 7).No significant difference was found in breast milkenergy content between groups at weeks 4, 8, and 12postpartum (Supplemental Figure 1).

Table 1. Mother’s characteristics at baseline and infant’s char-acteristics at birth.

CharacteristicsInterventionN¼ 113

ControlN¼ 113 p Value

Age (years), mean (SD) 23.9 (2.7) 24.1 (3.0) .8142a

Self-reported pre-pregnantBMI (kg/m2), mean (SD)

19.2 (1.8) 19.2 (1.8) .8203b

Mid-upper arm circumference,mean (SD)

24.1 (1.9) 24.2 (2.4) .7471b

Wealth index score 0.06 (1.59) �0.04 (1.62) .6673a

Education level, n (%) .7081c

Primary 1 (0.9) 2 (1.8)Secondary 27 (23.9) 32 (28.3)High school 43 (38.1) 36 (31.9)College/University 42 (37.2) 43 (38.1)Delivery mode, n (%) .4872c

Normal delivery 76 (68.5) 80 (72.7)C-section 35 (31.5) 30 (27.3)Gestational age, mean (SD) 39.1 (1.3) 39.1 (1.6) .8026a

Infant’s sex, n (%) .9503c

Male 60 (54.1) 59 (53.6)Female 51 (46.0) 51 (46.4)Birth weight (g), mean (SD) 3153 (347) 3044 (385) .0346a

Birth length (cm), mean (SD) 49.0 (1.7) 48.7 (2.2) .5195a

Head circumference (cm), mean (SD) 33.1 (1.3) 32.7(1.6) .1204a

ap Value is from Wilcoxon test.bp Value is from T-test.cp Value is from Chi-square test.

Figure 2. EBF rates at weeks 4, 8, and 12 postpartum p values is from GEE analysis controlling for mother’s age and MUAC atbaseline, infant gender, delivery mode, and study sites.

1590 D. T. T. HUYNH ET AL.

Birth outcomes

The infants in the intervention had significantly higherBW (p¼ .0312), BW-for-age (p¼ .0141), and HC-for-agez-score (p¼ .0487), compared with the control(Table 3). There was a trend toward higher birth HC inthe intervention group (p¼ .0886) (Table 3). The per-centage of infants with birth HC-for-age <�2 SD inthe intervention group was significantly lower thanthe control (p¼ .0182) (Supplemental Figure 2).

Longitudinal growth over the first 12weeks of life

The longitudinal growth of HC and HC-for-age z-scorein the intervention group were significantly higherthan the control group (p¼ .0473 and p¼ .0183,respectively), adjusting for potential confounders(Table 3). There were trends for higher weight-for-agez-score (p¼ .0636) and length-for-age z-score(p¼ .0690) development over time in the interventiongroup, compared to the control group.

Maternal energy and macronutrient intakes

At baseline, more than two thirds of women in bothgroups had inadequate intakes of calcium, iron, zinc,vitamin A, vitamin E, vitamin B2, and folate (Figure 3).At 12 weeks postpartum, nearly 100% of mothers inthe intervention group had adequate intakes of cal-cium, zinc, vitamin E, vitamin C, and B-vitamins, exceptfor folate. In contrast, more than three-quarters of thebreastfeeding women in the control group continuedto have inadequate intake of calcium, zinc, vitamin E,and vitamin B2.

Although women in the intervention group had sig-nificantly higher intakes of energy, protein and carbo-hydrate (Supplemental Table 8), body weight, and BMIof this group were similar to the control group over thestudy period (both p> .05) (Supplemental Figure 3).

Adverse events (AEs) were reported in 17 (15.0%)and 11 (9.7%) mothers in the intervention and controlgroups, respectively. The majority of AEs were gastro-intestinal disorders with seven AEs in the interventiongroup and six AEs in the control group. Overall, therewere no statistically significant differences or clinicallyrelevant trends between the groups for any system-related AEs. In terms of serious adverse events (SAEs),there were 68 mothers (35 [31.0%] in the interventiongroup and 33 [29.2%] in the control group) with atleast 1 SAE. The majority of SAEs were for conditionsoccurring during labor and delivery. The most fre-quently reported cause for C-section delivery was forcephalo-pelvic disproportion, which was reported by11 (9.7%) mothers in the intervention group and 8(7.1%) subjects in the control group. There were nostatistically significant differences between the groupsor clinically relevant trends for any SAEs (data notshown).

Table 2. Effect of maternal milk supplementation and breast-feeding support on infant’s breast milk intake over 12weekspostpartum among mothers with baseline MUAC <50thpercentile.

MUAC <50 percentile

Breast milkintake (g)

InterventionN¼ 54

ControlN¼ 47 p Value

PostpartumWeek 4 659.7 (218.7) 584.7 (189.2) .1066a

Week 8 664.6 (201.3) 610.7 (233.6)Week 12 695.1 (209.1) 646.5 (234.6)

GEE analysis over 12 weeks postpartumEstimate of treatment effect 64.2 (9.9, 118.0) Reference .0251b

ap Value is from the preliminary GEE model.bp Value is from GEE analysis controlling for mother’s age, MUAC, wealthindex score, infant gender, study site, and visit.Infant breast milk intake data is expressed as mean (SD).

Table 3. Effects of MNS and breastfeeding support on birth outcomes and growth outcomes from birth to 12weeks of postnatalperiod.

Estimate (95%CI)

Growth parameters Intervention (n¼ 104) Control (n¼ 100) p Value

Birth outcomes Birth weight (g) 92 (8,176) Reference .0312a

Birth length (cm) 0.1 (�0.3, 0.6) Reference .5452a

Birth head circumference (cm) 0.3 (0.0, 0.6) Reference .0886a

Birth weight-for-age z-score 0.25 (0.05, 0.45) Reference .0141b

Birth length-for-age z-score 0.18 (�0.10, 0.46) Reference .2116b

Birth head circumference-for-age z-score 0.31 (0.00, 0.62) Reference .0487b

Longitudinal growth from birth to 12 weeks Weight (g) 68.7 (�34.2, 171.7) Reference .1922c

Length (cm) 0.27 (�0.1, 0.6) Reference .1419c

Head circumference (cm) 0.26 (0.005, 0.52) Reference .0473c

Weight-for-age z-score 0.16 (�0.03, 0.36) Reference .0636d

Length-for-age z-score 0.19 (�0.01, 0.39) Reference .0690d

Head circumference-for-age z-score 0.28 (0.05, 0.51) Reference .0183d

ap Value is from ANCOVA analysis controlling for gestational age and infant gender.bp Value from ANCOVA analysis controlling for mother’s age, mother’s MUAC at baseline, wealth index score, gestational age, infant’s sex, and visit.cp Value from GEE analysis controlling for mother’s age, mother’s MUAC at baseline, wealth index score, gestational age, infant’s sex, and visit.dp Value is from GEE analysis controlling for mother’s age, wealth index score, infant gender, visit, and study site.

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Discussion

In this study, MNS during the last trimester of preg-nancy significantly improved birth outcomes inVietnamese mothers. Combining MNS with a breast-feeding support program during postpartum periodincreased and sustained EBF rate, and promoted post-natal growth in the offspring. In addition, the interven-tion increased breast milk production among motherswith baseline MUAC<24.1 cm.

In the present study, MNS consumption during thelast trimester of pregnancy was effective in promotingbetter birth outcomes including BW, BW-for-age, andbirth HC-for-age z-scores, as well as reducing the riskof birth HC-for-age <�2 z-scores. Our findings areconsistent with previous studies demonstrating thepositive impact of MNS containing energy and proteinduring pregnancy on improving BW and reducing therisk of SGA [8]. To our knowledge, only one studyreported a significant increase in the crude birth HCmeasurements by 3.1mm in chronically undernour-ished women around 20weeks gestation receiving ahigh-energy supplement of 1017 kcal, 22 g protein,and 56 g fat compared with an unsupplemented con-trol group [27]. Our findings suggest that MNS con-sumption during the last trimester improves the intakeof nutrients important to fetal growth and develop-ment, and thereby improves birth outcomes andreduces risk of SGA in this population.

Numerous studies showed that breastfeeding sup-port with formal or structured breastfeeding educationduring prenatal, postnatal, or combined, significantlyincreased EBF rates during the first 6months postpar-tum [28]. However, an intensive breastfeeding supportprogram including hospital counseling visit and sevenhome visits during 4months postpartum showed toincrease EBF but did not affect infant milk intake asmeasured by an isotopic method [29]. On the otherhand, a randomized, double-blind study in undernour-ished mothers in Guatemala showed that high-energyfood supplementation from 5 to 25weeks postpartumsustained the EBF rate better than the control group[16]. The same study also found higher infant’s milkintake (by 64 g/day at weeks 25) among those whowere more severely undernourished, defined as calfcircumference �29.5 cm. In the present study, ourintervention aimed to promote adequate nutritionalintakes during pregnancy and breastfeeding throughMNS, coupled with the provision of breastfeeding sup-port. The intervention significantly improved and sus-tained EBF rate over 12weeks postpartum. Similar tothe Guatemala study, we also found significantlyhigher infant’s milk intake (64 g/day over the 12weeks)in the intervention group among mothers with MUACbaseline <24.1 cm when compared with the controlgroup, despite that women in our study had highermean BMI and MUAC at weeks 4 postpartum

13.3

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8.8

15.910.6

67.3

79.6

24.8

50.4

38.9

14.2

31.9

100.0c

10.6c

100.0c

60.6c

100.0c 100.0c 100.0b 100.0c99.0c 100.0c

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16.8

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InterventionControl

12 weeks postpartumBaseline

Figure 3. Percentage of mothers with adequate intake of selected vitamins and minerals by study group at baseline and at week12 postpartum. p Value is from Chi-square test. ap< .05. bp< .001. cp< .0001

1592 D. T. T. HUYNH ET AL.

compared to Guatemala study. As there were no sig-nificant between-group differences in the number ofnursing episodes during 24-h test weighing and thenursing duration at most postpartum time points, it ispossible that the increased infant’s milk intake is dueto the increased breast milk production in the supple-mented mothers with baseline MUAC<24.1 cm.Collectively, the results from our study and previousresearch suggest that combining MNS (during preg-nancy and breastfeeding) and breastfeeding supportincrease breast milk production to enable mothers toexclusively breastfeed, and this effect appears to bemore pronounced among mother with lower baselinenutritional status.

The present study also showed that continuation ofMNS during breastfeeding period improved headgrowth over time, in both actual measurement, andsex- and age-specific z-scores. The significantly higherinfant weight at birth was weakened in trend over the12-week postnatal period. This could be explained bythe lower rate of EBF in the control group leading tosupplementing breast milk with formula, which isknown to have higher energy content compared withbreast milk. Although birth length was not significantlydifferent between groups, the trend of greater length-for-age z-score development over time was observedin the intervention group. The trend of higher breastmilk intake was not statistically significantly differentbetween groups. Therefore, we expected the milkenergy and macronutrients to be of higher concentra-tions in the intervention compared with the controlgroup. However, we did not observe this probablybecause of single milk sampling instead of multiplesamplings over a 24-h period where the concentrationof fat, lactose, and total protein were shown to beassociated with feeding patterns, and therefore variedover the 24-h period [30,31].

The present study has some limitations. This was anonblinded open-label study design; therefore therecould be a risk of bias in the process of administeringthe study procedures to the two study groups, as wellas the identification or reporting of interested out-comes due to knowledge of the subjects’ treatmentstatus. However, we implemented blinded assessor tominimize the risk of bias. Although test weighing forassessing infant’s breast milk intake is commonly used,its limitations have been discussed [32]. The use of asingle 24-h food recall imparts limitations on sufficientcharacterization of a subject’s usual intake as a resultof day-to-day variation. Lastly, we do not have pro-spective data on EBF at 6months for evaluating theimpact of the intervention in increasing the EBF rateat 6months as recommended by WHO.

In summary, continuation of maternal milk supple-mentation from the last trimester to the first 12weekspostpartum, coupled with breastfeeding supportshowed to improve birth outcomes and EBF rates,when compared with the current pre- and postnatalcare. This intervention model also increased breastmilk production in Vietnamese mothers with preg-nancy MUAC<24.1 cm. Given that the right nutritionduring the first 1000 day window has a profoundimpact on a child’s ability to grow, learn, and thriveand that poor nutrition early in life has lasting effectson lifelong health [6]. The findings of this study sug-gest a low-fat and nutrient-dense MNS during preg-nancy and breastfeeding has a positive impact onimproving growth during this critical window.

Acknowledgements

We would like to thank participating women. Special thanksto the study team of Abbott Nutrition and the study team ofNIN, Hai Phong, Ha Nam, Ninh Binh and Thai NguyenProvinces for coordination and assistance during study exe-cution. We thank Agnes Siew Ling Tey for her helpful com-ments on the earlier draft of the manuscript.

Disclosure statement

D.T.T.H. and Y.L.L. are employees of Abbott Nutrition. Y.B. isan employee of Cognizant Technologies Solution Pvt. Ltd, aContract Research Organization providing statistical servicesto Abbott Nutrition.

Funding

The study was funded by Abbott Nutrition. Abbott Nutritionwas responsible for the study design, monitoring, data ana-lysis and manuscript preparation and submission.

References

[1] Victora CG, de Onis M, Hallal PC, et al. Worldwide tim-ing of growth faltering: revisiting implications forinterventions. Pediatrics. 2010;125:e473–e480.

[2] Dewey KG. Reducing stunting by improving maternal,infant and young child nutrition in regions such asSouth Asia: evidence, challenges and opportunities.Matern Child Nutr. 2016;12 Suppl 1:27–38.

[3] Wrottesley SV, Lamper C, Pisa PT. Review of theimportance of nutrition during the first 1000 days:maternal nutritional status and its associations withfetal growth and birth, neonatal and infant outcomesamong African women. J Dev Orig Health Dis.2016;7:144–162.

[4] Picciano MF. Pregnancy and lactation: physiologicaladjustments, nutritional requirements and the role ofdietary supplements. J Nutr. 2003;133:1997S–2002S.

THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 1593

[5] Black RE, Victora CG, Walker SP, et al. Maternal andchild undernutrition and overweight in low-incomeand middle-income countries. Lancet. 2013;382:427–451.

[6] Christian P, Mullany LC, Hurley KM, et al. Nutritionand maternal, neonatal, and child health. SeminPerinatol. 2015;39:361–372.

[7] Ahmed T, Hossain M, Sanin KI. Global burden ofmaternal and child undernutrition and micronutrientdeficiencies. Ann Nutr Metab. 2012;61 Suppl 1:8–17.

[8] Imdad ABhutta ZA. Maternal nutrition and birth out-comes: effect of balanced protein-energy supplemen-tation. Paediatr Perinat Epidemiol. 2012;26 Suppl1:178–190.

[9] Papathakis PC, Singh LN, Manary MJ. How maternalmalnutrition affects linear growth and developmentin the offspring. Mol Cell Endocrinol. 2016;435:40–47.

[10] Haider BABhutta ZA. Multiple-micronutrient supple-mentation for women during pregnancy. CochraneDatabase Syst Rev. 2017;(4):CD004905.

[11] Vaivada T, Gaffey MF, Das JK, et al. Evidence-basedinterventions for improvement of maternal and childnutrition in low-income settings: what's new? CurrOpin Clin Nutr Metab Care. 2017;20:204–210.

[12] Cetin ILaoreti A. The importance of maternal nutritionfor health. J Pediatr Neonat Individual Med. 2015;4:e040220.

[13] Berti C, Cetin I, Agostoni C, et al. Pregnancy andinfants’ outcome: nutritional and metabolic implica-tions. Crit Rev Food Sci Nutr. 2016;56:82–91.

[14] Marangoni F, Cetin I, Verduci E, et al. Maternal dietand nutrient requirements in pregnancy and breast-feeding. Nutrients. 2016;8:629.

[15] Rasmussen KM. The influence of maternal nutrition onlactation. Annu Rev Nutr. 1992;12:103–117.

[16] Gonzalez-Cossio T, Habicht JP, Rasmussen KM, et al.Impact of food supplementation during lactation oninfant breast-milk intake and on the proportionof infants exclusively breast-fed. J Nutr. 1998;128:1692–1702.

[17] Garcia AH, Voortman T, Baena CP, et al. Maternalweight status, diet, and supplement use as determi-nants of breastfeeding and complementary feeding: asystematic review and meta-analysis. Nutr Rev.2016;74:490–516.

[18] NIN. Summary report: General Nutrition Survey2009–2010. Ha Noi, Vietnam: National Institute ofNutrition, Ministry of Health; 2012.

[19] Laillou A, Pham TV, Tran NT, et al. Micronutrient defi-cits are still public health issues among women andyoung children in Vietnam. PLoS One. 2012;7:e34906.

[20] Nakamori M, Ninh NX, Isomura H, et al. Nutritionalstatus of lactating mothers and their breast milk con-centration of iron, zinc and copper in rural Vietnam.J Nutr Sci Vitaminol. 2009;55:338–345.

[21] WHO. Global strategy for infant and young child feed-ing. Geneva, Switzerland: World Health Organization;2003.

[22] WHO. WHO Child Growth Standards based on length/height, weight and age. The WHO Multicentre GrowthReference Study. Acta Paediatr Suppl. 2006;450:76–85.

[23] Lee PA, Chernausek SD, Hokken-Koelega AC, et al.International Small for Gestational Age Advisory Boardconsensus development conference statement: man-agement of short children born small for gestationalage, April 24-October 1, 2001. Pediatrics. 2003;111:1253–1261.

[24] WHO. The quantity and quality of breast milk: reporton the WHO collaborative study on breastfeeding.Geneva, Switzerland: World Health Organization; 1985.

[25] Gibson SR. Evaluation of nutrient intakes and diets. In:S.R. Gibson, editor. Principles of nutritional assess-ment. New York: Oxford University Press; 2005. p.197–228.

[26] Filmer DPritchett LH. Estimating wealth effects with-out expenditure data-or tears: an application to edu-cational enrollments in states of India. Demography.2001;38:115–132.

[27] Ceesay SM, Prentice AM, Cole TJ, et al. Effects on birthweight and perinatal mortality of maternal dietarysupplements in rural Gambia: 5 year randomised con-trolled trial . BMJ. 1997;315:786–790.

[28] Imdad A, Yakoob MY, Bhutta ZA. Effect of breastfeed-ing promotion interventions on breastfeeding rates,with special focus on developing countries. BMCPublic Health. 2011;11:S24.

[29] Albernaz E, Victora CG, Haisma H, et al. Lactationcounseling increases breast-feeding duration but notbreast milk intake as measured by isotopic methods.J Nutr. 2003;133:205–210.

[30] Mitoulas LR, Kent JC, Cox DB, et al. Variation in fat,lactose and protein in human milk over 24 h andthroughout the first year of lactation. Br J Nutr.2002;88:29–37.

[31] Khan S, Hepworth AR, Prime DK, et al. Variation in fat,lactose, and protein composition in breast milk over24 hours: associations with infant feeding patterns.J Hum Lact. 2013;29:81–89.

[32] Scanlon KS, Alexander MP, Serdula MK, et al.Assessment of infant feeding: the validity of measur-ing milk intake. Nutr Rev. 2002;60:235–251.

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