Background: Risk factors known to impact maternal and newborn nutrition and health can exist from adolescence. If an undernourished adolescent girl becomes pregnant, her own health and pregnancy are at an increased risk for adverse outcomes. Offering preconception care from adolescence could provide an opportunity for health and nutrition promotion to improve one’s own well-being, as well as future pregnancy outcomes and the health of the next generation. Methods: The Matiari emPowerment and Preconception Supplementation (MaPPS) Trial is a population-based two-arm, cluster-randomized, controlled trial of life skills building education and multiple micronutrient supplementation provided in a programmatic context to evaluate the impact on pre-identified nutrition and health outcomes among adolescent and young women (15–24 years) in Matiari district Pakistan, and the infants born to them within the context of the trial. The primary aim is to assess the effect of the intervention on the prevalence of low birth weight births (< 2500 g). The intervention includes bi-monthly life skills building education provided from preconception, and supplementation with multiple micronutrients during preconception (twice-weekly), pregnancy (daily), and post-partum (daily to 6 months). The standard of care includes non-regulated community-based health sessions and daily iron and folic acid supplementation during pregnancy. Additional outcome information will also be collected at set time periods. Among participants, these relate to nutrition (anthropometry, nutritional status), morbidity, and mortality. Among infants, these include birth outcomes (stillbirth, preterm birth, length of gestation, small for gestational age, birth defects), anthropometry, morbidity, and mortality. (Continued on next page) * Correspondence: email@example.com; firstname.lastname@example.org Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Baxter et al. Reproductive Health (2018) 15:104 Page 2 of 13 (Continued from previous page) Discussion: Preconception care from adolescence that includes interventions targeting life skills development and nutrition is suggested to be important to improving the health and nutrition of adolescent and young women and their future offspring. This study is expected to offer insight into providing such an intervention both within a programmatic context and with an extended exposure period prior to conception. Trial registration: The MaPPS Trial was registered retrospectively on clinicaltrials.gov (Identifier: NCT03287882)on September 19, 2017. Keywords: Adolescence, Young adult, Nutrition, Micronutrients, Education, Preconception, Low birth weight, Pregnancy, Empowerment Plain English summary 15–19 years of age, and more than 90% of these occur in Proper nutrition during pregnancy is important to the low- and middle-income countries (LMICs), providing ap- good health of mothers and their infants. However, many propriate interventions prior to and during pregnancy will women in low- and middle-income countries who become be crucial to reducing the burden of adverse outcomes . pregnant have poor nutrition, and this can affect the out- Antenatal care (ANC) services offer an opportunity for come of their pregnancies and the health of their infants. maternal screening and intervention during pregnancy. If a well-nourished woman becomes pregnant, she is more However, in LMICs women tend not to report for care likely to be healthy, have a healthy pregnancy, and give until the second trimester , thus the initial 100–150 of birth to a healthy infant. In this study, we aim to improve the first 1000 days are frequently missed. This presents a the nutrition and health of adolescent and young women major limitation to ensuring adequate uptake of interven- (15–24 years) in rural Pakistan before they become preg- tions for a reasonable duration, even though factors like nant, and so that they might be better nourished before nutritional status are crucial from the time of conception becoming pregnant. To improve participants’ nutrition for placentation, organogenesis, prevention of congenital and health, we will provide life skills building education birth defects, and fetal growth [7–9]. Given the risks asso- and multiple micronutrient supplements before they be- ciated with anemia during pregnancy, iron and folic acid come pregnant and until 6 months after they give birth if (IFA) supplementation is the standard of care during they become pregnant. Because adolescent and young ANC . Many experts have come to suggest that mul- women in rural Pakistan are known to be undernourished tiple micronutrient (MMN) supplementation should re- and have babies early in life, they could benefit from this place IFA given the prevalence of MMN deficiencies in intervention. To determine the effect of the intervention, LMICs, multiple causes of anemia, and synergistic interac- we will compare it to the care that women normally re- tions between micronutrients within biological processes ceive within the existing public health system. The main [6, 11]. MMN supplementation during pregnancy can sig- measurement that we will compare is how many infants nificantly decrease the risk of LBW births (relative risk: are born with a birth weight that is low (< 2500 g), which 0.88; 95% confidence interval: 0.85 to 0.91; high-quality suggests that the infants did not grow well during the evidence) compared to IFA , and among undernour- pregnancy. Ultimately, we hope that the findings from ished and anemic pregnant women MMN supplements this study will help us to understand what care should could further improve infant survival and birth outcomes be given to women in places with poor nutrition before . At this time, MMN supplementation has been nei- they become pregnant so that they have healthier ther accepted nor recommended by the World Health pregnancies. Organization . Offering preconception care from adolescence could pro- Background vide an opportunity for health and nutrition promotion to While the focus of global public health experts has been improve one’s own well-being, as well as future pregnancy on the first 1000 days of life as the most developmentally outcomes and the health of the next generation . In- critical period, risk factors known to impact maternal cluding a life skills building education (LSBE) component and newborn health can exist from adolescence . If an around empowering adolescent and young women to make adolescent girl becomes pregnant, her pregnancy is at an informed health-related decisions will be key to sustainable increased risk for adverse outcomes, including preterm and proficient uptake , as will be addressing underlying birth and low birth weight (LBW) . Furthermore, MMN insufficiencies . Currently, there is a paucity of births to adolescent mothers can negatively affect both well-designed, interventional trials around the provision of the mother and infant’s health in the future [3, 4]. As MMN supplements preconceptionally. There are 4 existing approximately 11% of all births are to adolescents trials which aim to investigate the efficacy of different Baxter et al. Reproductive Health (2018) 15:104 Page 3 of 13 preconception MMN supplements on birth outcomes within the context of the trial. Depending on whether par- within a trial setting (Table 1)[16–19]. Among the com- ticipants become pregnant or not, there are three phases: pleted studies, the extent to which preconception MMN preconception (maximum 24 months in duration); preg- supplementation has affected each study’srespectivepri- nancy (approximately 9 months in duration); and postpar- mary outcome is variable. tum (maximum 12 months in duration). A detailed trial We hypothesize that the programmatic provision of protocol has been developed in accordance with the SPIRIT LSBE and MMN supplements in a population-based set- guidelines  in a collaboration between the Aga Khan ting in rural Pakistan will improve selected health, nutri- University (AKU; Karachi, Pakistan) and the Hospital for tion, and pregnancy-related outcomes among adolescent Sick Children (Toronto, Ontario, Canada). This paper ad- and young women 15–24 years old compared to those dressesthe methodsfor thepregnancy and postpartum who receive the standard of care. For those who receive phases of the MaPPS Trial, with the methods for ongoing the intervention prior to and during pregnancy, we ex- measures taken throughout the preconception phase pect that there will be a decrease in the prevalence of among participants who do not become pregnant appear- LBW births. Conducting this trial within the context of ing elsewhere . the existing Pakistani public health program, we will as- The first participant was enrolled on 30 June 2017; sess the effectiveness of the intervention. enrolment is expected to be ongoing until July 2018; and planned data collection will continue until 2021. Methods The Matiari emPowerment and Preconception Supplemen- Objectives tation (MaPPS) Trial is a two-arm, cluster-randomized, The primary aim of the pregnancy and postpartum phases controlled trial of LSBE and MMN supplementation pro- of the MaPPS Trial is to evaluate the impact of LSBE vided in a programmatic context to evaluate the impact on (provided bi-monthly) and supplementation with MMN pre-identified nutrition and health outcomes among adoles- (preconception: twice-weekly; pregnancy: daily) versus the cent and young women, and the infants born to them standard of care (non-regulated community-based health Table 1 Summary of ongoing and completed interventional trials investigating preconceptional multiple micronutrient supplementation Study name Years active Country No. arms Intervention Minimum exposure to intervention Potdar 2014  2006–2011 India 2 Arm 1: preconception: daily 3 months (Mumbai Maternal micronutrient-rich food snack; Nutrition Project) pregnancy: daily micronutrient rich food snack Arm 2: preconception: daily micronutrient-poor food snack; pregnancy: daily micronutrient poor food snack Hambidge 2014  2013– ongoing multi-site 3 Arm 1: 3 months (Women First Study) (Congo, Guatemala, preconception: daily MMN India, Pakistan) via lipid-based nutrient supplements (LNS) pregnancy: daily MMN via LNS Arm 2: preconception: none pregnancy: daily MMN via LNS Arm 3: preconception: none pregnancy: none Owens 2015  2006–2008 The Gambia 2 Arm 1: preconception: daily not specified UNIMMAP preparation tablet; pregnancy: daily IFA tablet Arm 2: preconception: placebo control; pregnancy: daily IFA tablet Ramakrishnan2016  2011–2013 Vietnam 3 Arm 1: preconception: weekly MMN not specified (PRECONCEPT) tablet; pregnancy: daily IFA tablet Arm 2: preconception: weekly IFA tablet; pregnancy: daily IFA tablet Arm 3: preconception: weekly FA tablet; pregnancy: daily IFA tablet Baxter et al. Reproductive Health (2018) 15:104 Page 4 of 13 sessions; preconception: no supplementation; pregnancy: Eligibility criteria daily IFA supplementation) on the prevalence of LBW As the MaPPS Trial is a population-based effectiveness births (< 2500 g). There are several secondary objectives study of LSBE and MMN supplementation from precon- for participants enrolled in the trial and the infants born ception, broad eligibility criteria for participation in the to them to further determine the effect of LSBE and preconception phase were established to improve the MMN supplementation compared to the standard of care. generalizability of the trial findings. Specifically, this in- Among participants, these relate to nutrition (anthropometry cludes that the minimum age at enrolment is 15 years [height, weight, middle upper arm circumference (MUAC)], and the maximum age is 23 years, such that participants nutritional status [iron, vitamin A, vitamin D]) and general will not age out of the trial prior to conception; adoles- health (e.g., morbidity, mortality). Among infants born to cent and young women must report to be physically participants, secondary objectives include assessing the able to comply with the trial intervention. Adolescent effect on birth outcomes (stillbirth, preterm birth, and young women are not eligible to enrol if they are length of gestation, small for gestational age, birth de- currently pregnant (to be re-approached after giving fects), anthropometry (weight, length, MUAC, head cir- birth), participating in a different nutrition trial, or in- cumference [HC]), morbidity, and mortality. tend to leave the trial area. They can be of any marital status. Setting and participants To proceed to the pregnancy phase of the MaPPS The MaPPS trial will be conducted in rural settings within Trial, participants will be included if they become preg- Matiari district in Sindh province, Pakistan. Matiari is situ- nant within 24 months of recruitment. To ensure ad- ated in the north-eastern part of Sindh, about 200 km equate exposure to the intervention, only women who away from Karachi, and representative of typical condi- become pregnant after 6 months of MMN supplementa- tions in rural Pakistan. Including 1418 villages and a tion will be formally considered a part of the per-protocol population of about 776,000, around 78,000 residents are MaPPS pregnancy phase. To maintain the relationship adolescent and young women 15–24 years (based on regu- with the local community, women in the intervention lar surveillance data). arm who become pregnant prior to 6 months of The nutritional status of Pakistani women is suggested MMN supplementation will be retained in the trial to be suboptimal, and often attributed to that dietary sta- and some routine data will be collected on them and ples are micronutrient poor [22, 23]. A comparable num- their pregnancies. To further be included in the post- ber of non-pregnant and pregnant women are anemic partum phase of the MaPPS Trial, a woman will have (51%) and experience iron deficiency anemia (20 and to have had a live birth. 26% among non-pregnant and pregnant women, re- spectively); deficiencies in other micronutrients are also common (e.g., vitamin A [43 and 49%] and vitamin D Design and sample size [85 and 86%]) . Infants born to Pakistani women The MaPPS Trial is a two-arm, parallel, prospective, are consequently at an increased risk of poor growth cluster-randomized, controlled trial (Fig. 1). A cluster- and development. The national prevalence of LBW is randomized design was chosen to prevent contamination 26%, yet this is higher among young mothers (29%) and between the control and intervention arms through sup- in rural areas (33%) . plement sharing. The unit of randomization is previously This trial is situated within Pakistan’sNationalProgram defined and mapped health facility clusters, where health for Family Planning and Primary Health Care as part of care services are provided to the surrounding popula- the Lady Health Worker (LHW) Programme. The LHW tion. A total of 26 clusters are available to be random- Programme aims to provide essential primary health ized (i.e., 13 clusters per arm). PASS 11 Software (NCSS, services in the community using a cadre of female com- LLC., Kaysville, UT, USA) was used to determine all munity health workers called LHWs . Each LHW is sample size calculations. affiliated with a health facility, where she reports to her To observe a 25% relative reduction in LBW births lady health supervisor (LHS), and is responsible for ap- (the a priori minimum detectable difference of public proximately 1000 people in the community. LHWs visit health importance for this trial) among pregnant the homes in their catchment area monthly and carry women 15–24 years, assuming a 30% prevalence of LBW, out community support sessions to disseminate health icc = 0.011, k = 0.16, accounting for 10% attrition and education messages . The priority age groups for probability of type I and type II errors of 0.05 and LHWs are children < 5 years, pregnant women, and 0.20, respectively, the number births required per couples eligible for family planning, thus the content of cluster was 56. This equates to 728 births per arm. existing LHW educational materials primarily focuses To achieve these births, 12,712 women per arm will on the health of married women and children . be required (total: 25,424 women). Baxter et al. Reproductive Health (2018) 15:104 Page 5 of 13 Fig. 1 Matiari emPowerment and Preconception Supplementation (MaPPS) Trial flow diagram Cluster randomization and allocation concealment will be implemented bi-monthly and attendance will be The cluster allocation sequence was generated by an in- recorded. Three topic areas were prioritized: (a) delaying dependent statistician (Simon Cousens, London School early marriage; (b) practicing appropriate personal and of Hygiene and Tropical Medicine) using a computer- menstrual hygiene; and (c) the importance of good nutri- generated stratification sequence in Stata software tion to health. Approximately 20 min is intended to be (StataCorp, College Station, TX, USA) based on the avail- spent on each topic at community sessions. Integrated able health facilities in the district. The list was provided throughout the 3 topics are messages related to continu- to the study manager, as full blinding is not possible given ing one’s education, mental health (how to cope with the nature of implementation of the intervention and con- stress, anxiety, and when you are upset), gender norms trol. Participants and LHWs are also not blinded given the and equality, decision-making, advocacy, resiliency, par- differences between the intervention and control. The pri- ticipation, communication skills, facing challenges, agency, mary investigator, co-investigators, data collectors, phle- conflict resolution, and the prevention of violence. botomists, laboratory personnel, and data analysts are Communication tools have been developed to assist the blinded to arm allocation. The allocation sequence will be LHWs in conducting the LSBE-based community ses- provided to the trial Data Safety and Monitoring Board sions. These were developed in coordination with Aahung, (DSMB) in cases where individual participants need to be a Karachi-based non-governmental organization that aims unblinded given a suspected MMN supplement-related to improve the sexual and reproductive health of girls adverse events. (www.aahung.org; Karachi, Pakistan). Communication tools include a flipchart with 2 pictorials and discussion prompts Intervention and control per topic for use in sessions; and a brief summary pamphlet LSBE materials for distribution to participants. The flipcharts are similar to In intervention clusters, enhanced LSBE materials have existing LHW tools for leading community sessions. A been developed on topics important to the empowerment team of master trainers will be trained on all LSBE mate- of adolescent and young women to complement the exist- rials and appropriate communication techniques. The mas- ing LHW materials for use in community sessions. These ter trainers, in turn, provide comprehensive and interactive Baxter et al. Reproductive Health (2018) 15:104 Page 6 of 13 training for all intervention LHWs. Refresher training will will take the MMN supplements until 6 months also be provided on an ongoing basis throughout the dur- postpartum. ation of the trial. During the preconception phase, participants are asked to consume 1 MMN tablet 2 days/week. To make the incorporation MMN supplementation into their routine Trial supplements easier, participants are requested to choose a consistent The MMN supplements used within the intervention time on 2 days in the week that are separate from each arm of the MaPPS Trial are consistent with the other (e.g., Monday and Thursday, or Wednesday and UNICEF/WHO/UNU international multiple micronutrient Saturday) on which to take 1 MMN tablet with a glass of preparation (UNIMMAP), and have been procured from water and a meal. Each participant is provided with a theUNICEFSupplyCatalogue (https://supply.unicef.org). 1 month supply of MMN supplements, plus a spare week Each tablet is 10 mm in diameter and includes vitamin A: in case of unscheduled missed visits. As such, participants 800 μg; vitamin D: 5 μg; vitamin E: 10 mg; folic acid: receive 10 MMN tablets/month (4 weeks/month × 2 400 μg; vitamin B1 (thiamine): 1.4 mg; vitamin B2 (ribofla- tablets/week + 2 extra tablets = 10 tablets total). During vin): 1.4 mg; vitamin B3 (niacin): 18 mg; vitamin B12: the pregnancy phase and for the first 6 months during 2.6 μg; vitaminB6: 1.9mg; vitaminC:70mg; iron:30mg; the postpartum phase, participants are asked to con- zinc: 15 mg; iodine: 150 μg; copper: 2000 μg; selenium sume 1 MMN tablet/day, given the higher daily micro- 65 μg (Micronutrient Tabs, Pregnancy; Lomapharm, nutrient requirements . As such, these participants Emmerthal, Germany). All MMN supplements are main- received 38 MMN tablets/month (31 days/month + 7 tained and stored by the study manager in a locked study extra tablets = 38 tablets total). office that is temperature controlled. A supply of MMN Participants are instructed that the MMN supplements supplements is provided to LHWs monthly by a study are just for them and should be kept away from children. monitoring team, which is unblinded to the allocation of They are asked to ensure that the lid of the supplement the intervention and not involved in data collection. Once bottle is tightly closed when not in use and stored away provided to participants, MMN supplements are stored in from light and humidity. It is also explained that some marked, opaque containers labelled with the participant’s people experience mild side effects when they start ID and supplement batch number and expiry date. taking the MMN supplements (e.g., nausea, vomiting, The IFA supplements are provided to the control arm diarrhea, stomach pains), but that taking it with food as part of Pakistan’s National Program for Family Planning should make side effects less likely to happen. If they and Primary Health Care free of charge . Each tablet is miss a dose, participants are instructed that they required to include iron and folic acid amounts consistent should take 1 MMN tablet the next time that they re- with WHO recommendations (i.e., 60 mg of elemental member, but never to consume more than 1 MMN iron and 400 μg of folic acid) . tablet/day. If a participant has any side effects, is con- Balanced-energy and protein (BEP) supplements will also cerned, or has questions, she is instructed to contact her be provided to those in the intervention and control arm if LHW and not study personnel since study personnel participants have a body mass index (BMI) < 18.5 kg/m are blinded to whether participants are in the control during pregnancy, as per WHO recommendations . or intervention arm. Participants are also asked not Each sachet weighs 75 g and includes energy: 360 kcal; total to take non-trial administered supplements while they fat: 24.8 g; carbohydrates: 19.5 g; protein: 9.9 g; sodium: are enrolled in the trial. 82.2 mg; potassium: 406.3 mg; vitamin A: 3.8 μg; vitamin C: 1.3 mg; calcium: 202.1 mg; iron: 0.87 mg (Afzaaish; Ismail Industries Ltd., Balochistan, Pakistan). Supplement administration - control arm (IFA) If a participant is in a control cluster, IFA supplements Supplement administration - intervention arm (MMN) will be administered within 1 week of confirmation of a Upon enrolment in the trial, intervention arm LHWs will pregnancy. Daily IFA supplementation is part of the stand- visit new participants within one month to provide the ard of care during pregnancy in Pakistan, thus LHWs are MMN supplements. A participant’s personal supply of asked to continue their usual counselling. As the LHW MMN supplements will be monitored and replenished program-supplied IFA supplements come in blister packs, every month by her respective LHW throughout her enrol- blister packs will be cut up to aid monitoring so that par- ment in the trial. If a participant does not become pregnant ticipants receive 38 IFA tablets/month (31 days/month + 7 within the context of the trial, she will take the MMN extra tablets = 38 tablets total), thus matching the method supplements for 24 months (the maximum duration of the of provision for the MMN supplements. As in the interven- preconception phase; majority of participants). If a partici- tion arm, a participant’s personal IFA supplement sup- pant becomes pregnant within the context of the trial, she ply is monitored and refilled every month by her respective Baxter et al. Reproductive Health (2018) 15:104 Page 7 of 13 LHW. Daily IFA supplementation is to continue until obtained as necessary. It is anticipated that enrolment 6 months postpartum. will take at least 1 year. Upon enrolment in the trial, a questionnaire designed to collect information on demographics; socioeconomic Supplement administration – Both arms (BEP) status (SES); reproductive health and history; life skills, Participants in the intervention and control arm with a 2 empowerment, and social determinants of health BMI < 18.5 kg/m will additionally be provided with (SDH)-related factors (Table 2); supplementation prac- daily BEP sachets for the duration of their pregnancy. tices; and access to LHWs will be administered. The Consistent with the other supplements consumed during questionnaire has been adapted from the existing pregnancy, BEP sachets will be provided and monitored demographic health survey for Pakistan and several monthly by LHWs (38 BEP sachets/month). standardized assessment tools. All participants will also undergo anthropometric (height, weight, MUAC) and Household listing hemoglobin concentration measurement. To identify young women who may be eligible to partici- pate in the MaPPS Trial, a household-level listing of those Visit schedule living in LHW-covered areas of Matiari district was com- All visits with trial participants will occur at their pleted. The household listing step is consistent with AKU’s homes. Each phase of the trial has a different number existing surveillance program within Matiari district, and of visits, depending on how long the participant took place from December 2016 – May 2017. It allowed remains in the respective phase. Participants who do for enumeration of the trial population and identification not become pregnant within the context of their of young women who met the age criteria for enrolment. enrolment will be followed maximally for 24 months in Adolescent and young women who met the age criteria the preconception phase. The majority of participants are were further asked questions to determine their potential expected to fall into this category, and the ongoing eligibility (i.e., screening questions about their intention to measurements collected during this time are described in remain in the trial area; involvement in other nutrition tri- detail elsewhere . als; and any complicated medical conditions that might Participants will be instructed about the appropriate prevent them from being able to take MMN tablets). signs to recognize pregnancy (e.g., amenorrhea), and amenorrhea will be assessed at monthly LHW visits. Enrolment Women who become pregnant or suspect they may be Adolescent and young women identified in the household pregnant will be asked to contact study personnel or listing as provisionally eligible are further contacted by their LHW, such that pregnancy confirmation might study data collectors at their homes to confirm their occur. Depending on when a participant becomes preg- potential interest and eligibility. Provisionally eligible par- nant, her exact length of time in the preconception ticipants will be invited to participate in the preconception phase will vary. Upon confirmation of pregnancy, partic- phase of MaPPS Trial in conjunction with their family ipants will be followed through to delivery. Participants members and/or husbands, and data collectors will and their family members will be asked to contact study explain the purpose and voluntary nature of the trial; personnel when labour begins. Furthermore, as LHWs participation components; and potential benefits and will visit with participants at least monthly for the harms prior to obtaining written informed consent. If duration of the trial and study personnel will visit at set participants are < 16 years of age, assent will also be times, good rapport will be established between Table 2 Factors relating to life skills, empowerment, and SDH captured within trial questionnaires Domains Includes information pertaining to Evaluation tool Nutrition Household food insecurity Household Food Insecurity Access Scale  Health Eating habits Health Behaviour in School-aged Children  Body image Physical activity Perception of support Family, peer, and school Multidimensional Scale of Perceived Social Support  Decision making Family, food, health care, and daily needs Pakistan Demographic Health Survey  Psychosocial health Self-efficacy Generalized self-efficacy scale  Stress Perceived stress scale  Mental health (depression, anxiety, and stress) Depression, Anxiety, and Stress Scale-21  Violence Intimate partner violence Conflict Tactics Scale  Exposure to violence Pakistan Demographic Health Survey  Baxter et al. Reproductive Health (2018) 15:104 Page 8 of 13 participants, their families and communities, LHWs, and draw. If a participant is found to have a BMI < 18.5 kg/m , study personnel, and all will be sensitized to notify of she will be provided with BEP supplements. Participants births as soon as possible. There are several additional will be encouraged to go to the most convenient public measures to capture birth-related outcomes in a timely sector health facility to obtain an ultrasound within 1 week manner, including having personnel dedicated to keeping of contact with data collectors. Among those who obtain in phone contact with the participant close to her due ultrasounds, data will be collected on crown-to-rump date and employing a standby birth surveillance team, length, estimated age, and general observations (fetal visibil- which is on call on holidays and weekends. Women who ity, multiple pregnancy, heart activity, signs of abnormality). give birth to a live infant will proceed to the postpartum At 32 weeks of gestation, participants will undergo a repeat phase. Mothers and their infants will be followed until anthropometric (height, weight, MUAC) and mental health 1 year postpartum. (EPDS) assessments. There will also be ongoing participant monitoring for the duration of the trial. Upon trial completion or with- drawal, participants will be asked to complete an exit Postpartum phase Mothers and newborns will be vis- questionnaire designed to assess their perception of their ited within 24 h of birth to obtain anthropometric mea- own health, the health of their infant, and satisfaction surements of the newborn (weight, length, MUAC, HC), with trial participation. assess of the status of the newborn (e.g., birth defects), and interview the mother about the birth (Table 4). At Pregnancy phase 1 week postpartum, maternal status, complications Given the frequent contact with and monitoring of par- during labour and delivery, and prelacteal and early ticipants, it is anticipated that most pregnancies will be breastfeeding practices will be assessed. Maternal an- recorded in the first trimester. Suspected pregnancies thropometric measurements (height, weight, MUAC) will be confirmed using a pregnancy test (HCG Rapid and a 5 mL blood draw will also be obtained. At Test; ImuMed, Bammental, Germany) provided by a par- 28 days postpartum, infant assessments will include mor- ticipant’s LHW. Confirmation of a pregnancy triggers bidity and anthropometry (weight, length, MUAC, HC). completion of the first trimester assessment (Table 3). Ongoing infant anthropometric and feeding assessments This includes formal collection of information on the (breastfeeding and complementary feeding practices) will participant’s last menstrual period, anthropometry (height, be conducted tri-monthly until the end of the trial (i.e., at weight, MUAC), and mental health (Edinburgh Postnatal 3, 6, 9, and 12 months). Maternal mental health (EPDS) Depression Score [EPDS])  by data collectors. All and anthropometric assessments will be reassessed at 3 participants will also be asked to undergo a 5 mL blood and 6 months postpartum, respectively. Table 3 Enrolment and pregnancy phase data collection and measurement activities Activity Enrolment Pregnancy 0 m 1st trimester 3rd trimester Consent X Demographics and SES X Reproductive health and history X Life skills, empowerment, and SDH X Mental health X X X Anthropometry X X X Hemoglobin X X Serum ferritin M X Hepcidin M X Transferrin receptor M X Infection indicators (CRP, AGP) M X Vitamin A M X Vitamin D M X Pregnancy confirmation X Ultrasound assessment X X: all participants; M: micronutrient status subgroup participants only Baxter et al. Reproductive Health (2018) 15:104 Page 9 of 13 Table 4 Postpartum phase data collection and measurement activities Activity Timing 24h1w1m3m6m9m12m Maternal Anthropometry X X Birth history X Life skills, empowerment, and SDH X Mental health X Hemoglobin X Serum ferritin X Hepcidin X Transferrin receptor X Infection indicators (CRP, AGP) X Vitamin A X Vitamin D X Infant Anthropometry X X X X X X Clinical assessment X Feeding assessment X X X X X Morbidity X X: all participants LHW visits Questionnaires Because LHWs are required to visit households in their For data collector-conducted visits with participants, tablets catchment area monthly, these visits will serve to moni- (Samsung Galaxy Tab. A T285; Samsung, Vietnam) will be tor menses, new marriages, and suspected pregnancies used to collect questionnaire data. The tablets run a throughout the duration of the trial, in addition to their custom-made data collection application, which includes mandated function . All trial-administered supple- built-in logic and range checks, developed using Java ment provision and consumption will also be recorded (Oracle Corporation, Redwood Shores, CA, USA) and at these visits. MySQL Lite (Oracle Corporation). LHW monitoring visits will use paper-based questionnaires given the large number Adherence, morbidity, and mortality monitoring of LHWs involved in the trial. All participants will further be visited by an independent surveillance team to collect morbidity and self-reported ad- Table 5 Monitoring data collection activities ongoing herencedataevery 3months(Table 5). These visits will also throughout the trial allow for the observance and collection of data on non-trial Measurement Monthly Quarterly administered nutritional supplement consumption. (LHW) (Monitoring Team) a b Adherence by pill count i Data collection c b Adherence by self-reported frequency i Data collection tools have been customized for each type of Side effects X visit, and data is collected orally given the low literacy rates Acceptability i in the trial population. Trained study personnel will collect all trial outcome data using questionnaires, anthropometric Morbidity (maternal and/or infant) X measurements, and point-of-care tests. Standardized oper- Mortality (maternal and/or infant) X ating procedures have been developed for all measures X: all participants; i: intervention group only in an effort to make data collection practices consistent. Adherence by pill count defined as number of tablets apparently consumed/ number of possible supplements consumed given days enrolled in the study Extensive training sessions will be provided, employing Among those women who become pregnant in the control group, measure classroom-based lectures, videos, hands-on practice, and will also be monitored at the indicated intervals from time of confirmation of pregnancy until 6 months postpartum mock interviews. As appropriate, training will be led by Adherence options by self-report during preconception include twice weekly, experienced personnel within the broader AKU network intermittently, or not at all; during pregnancy and postpartum include daily, (e.g., data management unit, laboratory). on alternate days, intermittently, or not at all Baxter et al. Reproductive Health (2018) 15:104 Page 10 of 13 Anthropometric measurements Data management For participant measurements, height will be measured Data collection tablets are collected from study personnel using a stadiometer (seca 213; seca, Hamburg, Germany); on a daily basis so that questionnaire data can be uploaded weight using a digital floor scale (seca 813); and MUAC to the AKU data management unit via a remote server using a measuring tape (seca 201). For infant measure- (Windows Server 2008 R2; Microsoft, Redmond, WA, ments, length will be measured using an infantometer USA). Questionnaire data collected on paper-based forms (seca 417), weight using an infant weigh scale (seca are visually checked by field site supervisors for complete- 354), and MUAC and HC using a measuring tape ness before being sent to the AKU data management unit (seca 201 and 212, respectively). All measurements will be on a weekly basis for entry into a database. Double data conducted in duplicate by two data collectors. In the entryisusedtoreducedataentry errors. The database was case that two measurement exceed the allowable dif- designed using MySQL software and entered using Visual ference (length: < 1.0 cm; weight: < 0.5 kg; HC: < 0.5 cm; FoxPro software (Microsoft). All collected data is kept MUAC: < 0.5 cm), a third measurement will be obtained. under lock and key, and anonymized through the use of The average (mean) of acceptable paired measures will be nine-digit participant identification codes. Data entered into used in analysis. Standardized operating procedures for the database is password protected. the anthropometric measurements were adapted from published reference materials . Outcome measures To determine the prevalence of LBW at delivery, the pri- mary outcome measure is birth weight < 2500 g. LBW will Point-of-care hemoglobin assessment then be subdivided into very LBW (< 1500 g) and extremely To assess hemoglobin concentration, the HemoCue® Hb LBW (< 1000 g). There are many additional secondary out- 301 System (HemoCue; Ängelholm, Sweden) will be used come measures within the trial related to nutrition and from blood collected via finger prick. health that will be also assessed (see Additional file 1). Blood specimen collection and laboratory analyses Statistical analysis Trained phlebotomists (blinded to cluster allocation) will For the primary outcome, the prevalence of LBW births conduct all blood specimen collection using standard will be compared by intervention arm, irrespective of sampling procedures developed by the AKU Nutrition maternal preconception supplementation duration or ad- Research Lab (NRL). At each sampling time point, 5 mL herence (intention-to-treat). The per-protocol analysis will of venous blood will be collected and stored in trace consider only those women with ≥6 months of exposure element-free vacutainer tubes (royal blue top; Greiner to the intervention. Because the prevalence of anemia and Bio-One, Monroe, NC, USA). Two drops of whole blood LBW are high in the trial population, an individual-level are immediately taken from the collection tube to assess analysis using generalized estimating equations (GEE) will hemoglobin concentration using the HemoCue® Hb 301 be employed to determine the estimate of the population System point of care test. Because all blood specimens average. Clustering will be accounted for within the GEE are collected at participants’ homes, they are then stored analysis. Sub-analyses will also be conducted, including in a cool box with ice packs to maintain a temperature determining whether there is a difference among those of 2–8 °C and protected from light exposure immedi- who received BEP and those who did not within and be- ately after sample collection. Whole blood samples are tween arms, and whether there was a difference between received at the Matiari field site lab within 4 h, where adolescent and young women. There are several potential the vacutainers are centrifuged to separate the serum determinants which will be considered as covariates, such from the red blood cells. The serum is pipetted into as age, parity, adherence, and SES. Relevant information 1.8 mL cryovials (red top; Thermo Fisher Scientific, will be collected at enrolment and throughout follow-up. Waltham, MA, USA) and covered in aluminium to pro- Summary estimates (e.g., means, proportions, counts) tect from light exposure. The cryovials are then stored will be reported with 95% confidence intervals. Dichot- between 2 and 8 °C, and transported in a cool box main- omous outcomes will be compared using risk ratios tained at 2–8 °C to the AKU NRL once per week. Upon with 95% confidence intervals, and the difference in arrival at the AKU NRL, samples are analysed or stored in continuous variables will be determined by comparing an ultra-low freezer maintained at − 70 °C for future use. means. P values less than 0.05 will be considered sta- Samples will be assessed for markers of nutritional status tistically significant. Statistical analyses will be con- (iron [ferritin, transferrin receptor, hepcidin], vitamin A ducted using Stata software. The plan for the analysis [retinol], and vitamin D [25(OH)D]) and inflammation of secondary objectives and outcome measures will be (c-reactive protein, alpha-1-acid glycoprotein; Table 6). presented elsewhere. Baxter et al. Reproductive Health (2018) 15:104 Page 11 of 13 Table 6 Assays and instruments used to determine constituents of interest from collected blood specimens Micronutrient Amount of serum (μL) Assay method Instrument used Iron Ferritin 200 Immunoturbidimetric assay method Cobas C311 Analyzer, Roche Diagnostics Transferrin receptor 200 Immunoturbidimetric assay method Cobas C311 Analyzer, Roche Diagnostics Hepcidin 150 Enzyme-linked immunosorbent assay (ELISA) Hepcidin-25, Bachem Vitamin A (retinol) 200 Quantitative-high performance liquid Agilent HPLC, 1200/1260 Infinity chromatography photodiode array detection Series with UV/PDA detection Vitamin D (25(OH)D) 400 Electrochemiluminescence protein binding assay Diasorin Analyzer, LIAISON Inflammation C-reactive protein 200 Immunoturbidimetric assay method Cobas C311 Analyzer, Roche Diagnostics Alpha-1-acid glycoprotein 200 Immunoturbidimetric assay method Cobas C311 Analyzer, Roche Diagnostics Study management Discussion The field research team is overseen by the study manager, Malnutrition prior to and during pregnancy can have and includes several different positions (Fig. 2). Of note, important consequences for survival, acute and chronic data collection and food recall teams are responsible for disease incidence, healthy development, and economic collecting most primary and secondary outcome data; sur- productivity . In this trial, we aim to assess the effect- veillance teams collect morbidity and supplement ad- iveness of providing LSBE and MMN supplements to herence data, as well as ongoing tracking of pregnancies adolescent and young women in rural Pakistan from and births; and monitoring teams are dedicated to coord- preconception, and compare this intervention with the inating with LHWs and conduct ongoing data collection standard of care on the prevalence of LBW births. In- quality checks. A DSMB has been developed including cluding a culturally-tailored educational piece aimed at external international members with expertise in a wide empowering participants to make informed decisions array of related disciplines (pediatric and adolescent about their health and well-being will be key to sustained medicine, statistics, and nutrition). These individuals will behavioural change throughout the life-course. By imple- provide expertise and recommendations relating to accu- menting the intervention within the LHW Programme, mulated data about study operations and participant we aim to gather important insight around how to achieve safety. When appropriate, they may be asked to make rec- coverage within the existing programmatic context. This ommendations relating to continuation, modification, or trial is distinctive in that it recruits both married and un- termination of the trial. The DSMB meets with the study married adolescent and young women. Consequently, we principal investigator and co-investigators to discuss pro- will be better able to ascertain the effect of the interven- gress on a quarterly basis. tion on in the context of pregnancy, as well as investigate Fig. 2 Organization of MaPPS Trial field research team Baxter et al. Reproductive Health (2018) 15:104 Page 12 of 13 the effect on several domains of health and nutrition in thank Simon Cousens for his assistance with cluster allocation and ongoing guidance pertaining to statistical analysis. the absence of pregnancy, as detailed elsewhere . The WHO has not recommended antenatal MMN sup- Funding plementation at this time ). The standard of care re- Financial support to conduct this trial was provided by the Bill & Melinda Gates Foundation and the World Food Programme. Neither funding body had any mains IFA supplementation, in spite of several large trials role in the conduction of the study or the preparation of this manuscript. that show that MMN supplementation is efficacious in improving diverse health outcomes and meta-analyses that Authors’ contributions have found that MMN supplementation could be more ef- ZAB conceived the trial and secured funding. JBB, ZAB, and SBS participated in the initial conceptualization, design, and writing of the study protocol. YW and ZS fective than IFA in preventing adverse pregnancy-related have contributed ongoing input around the design, study protocol development, health outcomes [12, 13]. Given that only around 50% of and data collection methods. YW, SBS, and ZS have implemented the study in anemia is suggested to be caused by low iron stores, Matiari District. YW oversees field operations. JBB produced the first draft of this manuscript, with input from ZAB, YW, SBS, and ZS. All authors reviewed this MMN supplementation could provide further benefit than manuscript and approved the final version. ZAB is the guarantor. IFA alone . Furthermore, improving stores from pre- conception could be of added benefit because adolescent Ethics approval and consent to participate Ethics approval for this trial was obtained from the Aga Khan University and young women would enter pregnancy with sufficient Ethics Review Committee on August 16, 2016 (Number: 4324-Ped-ERC-16); pregnancy stores. and from the Research Ethics Board at the Hospital for Sick Children on Overall, the MaPPS Trial is expected to offer insight November 17, 2016 (Number: 1000054682). All women enrolled in the trial are asked for their written consent to participate in the trial and are free to into providing an intervention that includes both LSBE decline or stop their participation at any time without any consequences. and MMN supplementation to adolescent and young women from preconception and for a sufficient duration Competing interests of time, and on the impact on their infants. So as to The authors declare that they have no competing interests. better understand the long-term effect of the intervention on development (e.g., growth and neurodevelopment) Publisher’sNote Springer Nature remains neutral with regard to jurisdictional claims in published and diseases outcomes among infants born to study maps and institutional affiliations. participants, we anticipate conducting further follow up studies in the future. Author details Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada. Department of Nutritional Sciences, University of Toronto, Toronto, Trial status 3 ON, Canada. Centre of Excellence in Women and Child Health, Aga Khan As of May 2018, participants are still being enrolled in University, Stadium Road, Karachi, Pakistan. the trial. Received: 14 May 2018 Accepted: 24 May 2018 Additional file References 1. Prentice AM, Ward KA, Goldberg GR, Jarjou LM, Moore SE, Fulford AJ, Additional file 1: Additional tables detailing secondary outcome measures Prentice A. Critical windows for nutritional interventions against stunting. and cut-points. Description of data: The additional file includes 3 tables Am J Clin Nutr. 2013;97(5):911–8. detailing secondary outcome measures for participants and their infants. 2. Ganchimeg T, Ota E, Morisaki N, Laopaiboon M, Lumbiganon P, Zhang J, et (DOCX 24 kb) al. Pregnancy and childbirth outcomes among adolescent mothers: a World Health Organization multicountry study. BJOG. 2014;121(Suppl 1):40–8. Abbreviations 3. Olausson PO. Teenage childbearing and long-term socioeconomic AKU: Aga Khan University; ANC: Antenatal care; BEP: Balanced energy and protein; consequences: a case study in Sweden. Fam Plan Perspect. 2001;33:70–4. BMI: Body mass index; DSMB: Data safety monitoring board; GEE: Generalized 4. World Health Organization. Adolescent pregnancy: unmet needs and estimating eqs.; HC: Head circumference; IFA: Iron and folic acid; LBW: Low birth undone deeds: a review of the literature and programmes. Geneva: World weight; LHS: Lady health supervisor; LHW: Lady health worker; LMIC: Low- and Health Organization; 2007. middle-income country; LNS: Lipid-based nutrient supplements; MaPPS 5. World Health Organization. WHO guidelines on preventing early pregnancy Trial: Matiari emPowerment and Preconception Supplementation Trial; and poor reproductive health outcomes among adolescents in developing MMN: Multiple micronutrient; MUAC: Middle-upper arm circumference; countries. Geneva: World Health Organization; 2011. NRL: Nutrition Research Lab; UNIMMAP: UNICEF/ WHO/UNU international multiple 6. Bhutta ZA, Das JK, Rizvi A, Gaffey MF, Walker N, Horton S, Webb P, Lartey A, micronutrient preparation; WHO: World Health Organization Black RE. Lancet nutrition interventions review group; maternal and child nutrition study group. Evidence-based interventions for improvement of Acknowledgements maternal and child nutrition: what can be done and at what cost? Lancet. The authors wish to acknowledge the entire MaPPS Trial study team for their 2013;382(9890):452–77. contributions to data collection, monitoring, logistics, and general study 7. Cetin I, Berti C, Calabrese S. Role of micronutrients in the periconceptional operation, particularly Qamaruddin Junejo (field supervisor). We would also period. Hum Reprod Update. 2010;16(1):80–95. acknowledge the collaboration of the following groups within District 8. Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M. Matiari: the District of Health, Lady Health Worker Programme, and Education Grantham-McGregor S, Katz J, Martorell R, Uauy R; maternal and child Department. We appreciate the ongoing assistance and support provided by nutrition study group. Maternal and child undernutrition and overweight in Imran Ahmed, Arjumand Rizvi, Rasool Bux, and the members of the Data low-income and middle-income countries. Lancet. 2013;382(9890):427–51. Management Unit at AKU; Didar Alam and members of the Nutrition 9. De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon P. Effects Research Lab at AKU for ongoing laboratory coordination and logistics; and and safety of periconceptional oral folate supplementation for preventing Mir Asghar Ali Khan and Ishrat Abbas for grant and budgetary assistance. We birth defects. Cochrane Database Syst Rev. 2015;12:CD007950. Baxter et al. Reproductive Health (2018) 15:104 Page 13 of 13 10. World Health Organization. WHO recommendations on antenatal Care for a 31. Currie C, Inchley J, Molcho M, Lenzi M, Veselska Z, Wild F. Health Behaviour Positive Pregnancy Experience. Geneva: World Health Organization; 2016. in School-aged Children (HBSC) Study Protocol: Background, Methodology, 11. Ramakrishnan U, Grant F, Goldenberg T, Zongrone A, Martorell R. Effect of and Mandatory items for the 2013/14 Survey. St. Andrews: CAHRU; 2014. women's nutrition before and during early pregnancy on maternal and 32. Zimet GD, Dahlem NW, Zimet SG, Farley GK. The multidimensional scale of infant outcomes: a systematic review. Paediatr Perinat Epidemiol. 2012; Percieved social support. J Pers Assess. 1988;52:30–41. 26(Suppl 1):285–301. 33. Schwarzer R, Jerusalem M. Generalized self-efficacy scale. In: Weinman J, Wright S, Johnston M, editors. Measures in health psychology: a user’s 12. Haider BA, Bhutta ZA. Multiple-micronutrient supplementation for women portfolio. Causal and control beliefs. Windsor: NFER-NELSON; 1995. p. 35–7. during pregnancy. Cochrane Database Syst Rev. 2017;4:CD004905. 34. Cohen S, Williamson G. Perceived stress in a probability sample of the 13. Smith ER, Shankar AH, Wu LS, Aboud S, Adu-Afarwuah S, Ali H, et al. United States. In: Spacapan S, Oskamp S, editors. The social psychology of Modifiers of the effect of maternal multiple micronutrient health: Claremont Symposium on applied social psychology. Newbury Park: supplementation on stillbirth, birth outcomes, and infant mortality: Sage; 1988. a meta-analysis of individual patient data from 17 randomised 35. Lovibond SH, Lovibond PF. Manual for the Depression Anxiety Stress Scales. trials in low-income and middle-income countries. Lancet Glob Health. Sydney: Psychology Foundation; 1995. 2017;5(11):e1090–100. 36. Straus MA. Measuring Intrafamily conflict and violence: the conflict tactics 14. Dean SV, Lassi ZS, Imam AM, Bhutta ZA. Preconception care: promoting (CT) scales. J Marriage Fam. 1979;41:75–88. reproductive planning. Reprod Health. 2014;11(Suppl 3):S2. 15. Dean SV, Lassi ZS, Imam AM, Bhutta ZA. Preconception care: nutritional risks and interventions. Reprod Health. 2014;11(Suppl 3):S3. 16. Potdar RD, Sahariah SA, Gandhi M, et al. Improving women's diet quality preconceptionally and during gestation: effects on birth weight and prevalence of low birth weight–a randomized controlled efficacy trial in India (Mumbai maternal nutrition project). Am J Clin Nutr. 2014;100(5):1257–68. 17. Hambridge KM, Krebs NF, Westcott JE, et al. Preconception maternal nutrition: a multi-site randomized controlled trial. BMC Pregnancy and Childbirth. 2014;14:111. 18. Owens S, Gulati R, Fulford AJ, Sosseh F, Denison FC, Brabin BJ, et al. Periconceptional multiple-micronutrient supplementation and placental function in rural Gambian women: a double-blind, randomized, placebo- controlled trial. Am J Clin Nutr. 2015;102(6):1450–9. 19. Ramakrishnan U, Nguyen PH, Gonzalez-Casanova I, Pham H, Hao W, Nguyen H, et al. Neither Preconceptional weekly multiple micronutrient nor Iron- folic acid supplements affect birth size and gestational age compared with a folic acid supplement alone in rural Vietnamese women: a randomized controlled trial. J Nutr. 2016;146(7):1445S–52S. 20. Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586. 21. Baxter JB, Wasan Y, Soofi SB, Suhag Z, Bhutta ZA. Feasibility and effect of life skills building education and multiple micronutrient supplements versus the standard of care on anemia among non-pregnant adolescent and young Pakistani women (15–24 years): a prospective, population based cluster- randomized trial. Reprod Health. 2018. 22. Aga Khan University. National Nutrition Survey 2011. In: Government of Pakistan; 2013. 23. National Institute of Population Studies (NIPS) [Pakistan] and ICF International. Pakistan Demographic and Health Survey 2012–13. Islamabad, Pakistan, and Calverton, Maryland, USA: NIPS and ICF International; 2013. 24. World Health Organization, Global Health Workforce Alliance. Pakistan's Lady Health Worker Programme: Global Health Workforce Alliance, World Health Organization, Case study. Geneva: World Health Organization; 2008. 25. Hafeez A, Mohamud BK, Shiekh MR, Shah SA, Jooma R. Lady health workers programme in Pakistan: challenges, achievements and the way forward. J Pak Med Assoc. 2011;61:210–5. 26. World Health Organization. Daily iron and folic acid supplementation in pregnant women: guideline. Geneva: World Health Organization; 2012. 27. United Nations Children’s Fund, World Health Organization. United Nations University. Composition of a multi-micronutrient supplement to be used in pilot programmes among pregnant women in developing countries. New York: UNICEF; 1999. 28. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh postnatal depression scale. Br J Psychiatry. 1987;150:782–6. 29. Cheikh Ismail L, Knight HE, Bhutta Z, Chumlea WC, International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). Anthropometric protocols for the construction of new international fetal and newborn growth standards: the INTERGROWTH-21st project. BJOG. 2013;120(Suppl 2):42–7. 30. Coates J, Swindale A, Bilinsky P. Household food insecurity access scale (HFIAS) for measurement of household food access: Indicator guide (v. 3). Washington: Food and nutrition technical assistance project, academy for educational Development; 2007.
Reproductive Health – Springer Journals
Published: May 31, 2018
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera