Description of the condition

The nutritional status of women prior to and during pregnancy plays a key role in fetal growth and development, and women's energy and protein requirements significantly increase during pregnancy (FAO/WHO/UNU 2004). Maternal undernutrition is still prevalent, especially in low‐ and middle‐ income countries (LMICs), with approximately 20% of women in Asia and 10% women in Africa having a low body mass index (BMI; less than 18.5 kg/m² in adult women) (Black 2013). Apart from low BMI, deficiencies of micronutrients, including iron, folate, calcium, and vitamins A and D are also prevalent in LMICs. In 2011 the global prevalence of anaemia among pregnant women was estimated to be 38.2% (WHO 2015). At least half of this anaemia burden is assumed to be due to iron deficiency, with the rest due to other conditions, including folate, vitamin B12 or vitamin A deficiencies; chronic inflammation; parasitic infections; and inherited disorders (Black 2013). Calcium and vitamin D deficiencies are also a major public health problem worldwide in all age groups; however, most countries are still lacking reliable data, particularly population representative data, with limited information on infants, children, adolescents and pregnant women (Palacios 2014). Globally, the prevalence of night blindness in pregnant women is estimated to be around 8%, affecting around 10 million women, with an estimated 15.3% of pregnant women worldwide having low serum retinol levels (Black 2013). Estimates suggest that 28.5% of the world's population, or 1.9 billion individuals, are iodine deficient (Black 2013). Additionally, undernutrition and micronutrient deficiencies increase the risk of infections, and in turn lead to further undernutrition (Black 2013).

Maternal undernutrition causes maternal and child morbidity and mortality, also contributing to low birth weight (LBW) and small‐for‐gestational‐age (SGA) births, which can lead to stunting, wasting and micronutrient deficiencies in children (Black 2013). The placenta forms the interface between maternal‐fetal circulations, which is critical for fetal nutrition and oxygenation (Belkacemi 2010), while the placental supply of nutrients to the fetus depends on its size, morphology, blood supply, and transporter abundance. An optimal maternal nutrient supply has a critical role in placental‐fetal growth and development, while a suboptimum maternal nutrition supply during pregnancy results in intrauterine growth restriction (IUGR) and newborns with LBW (Belkacemi 2010). Maternal iron deficiency anaemia has been strongly associated with adverse birth outcomes, including LBW and increased perinatal mortality, while maternal zinc and iodine deficiencies have been suggested as risk factors for adverse fetal and infant growth (Black 2013). LBW, defined by the World Health Organization (WHO) as weight‐at‐birth of less than 2500 g (5.5 lb), continues to be a significant and global public health problem. Overall, about 15% to 20% of all births worldwide are LBW, representing more than 20 million births a year (WHO 2014). LBW is not only a major predictor of mortality and morbidity in infants and children, but recent studies have found that it also increases the risk for non‐communicable diseases, such as diabetes and cardiovascular disease, in later life (Larroque 2001; Risnes 2011). Nutriton is one of the factors influencing cognitive development, and there is some evidence that these nutritional deficiencies can impair child cognition (Shenkin 2004), as well as pose adverse health outcomes in adulthood (Harder 2007). Literature suggests that there is a connection between improved nutrition and optimal brain function since nutrients provide building blocks in cell proliferation, DNA synthesis, neurotransmitter and hormone metabolism, and they are important constituents of enzyme systems in the brain (Bhatnagar 2001; De Souza 2011; Lozoff 2006; Zeisel 2006; Zimmermann 2011). Brain development is faster in the early years of life, making children more vulnerable to maternal and early life dietary deficiencies (Nyaradi 2013).

Addressing undernutrition by achieving appropriate energy intakes (in the form macronutrients) and ensuring that the intakes of specific nutrients (like vitamins and minerals) are adequate to meet maternal and fetal need, is of the utmost importance for improving maternal and child health outcomes (Imdad 2011). Early preventive measures could address general deprivation and inequity, leading to substantial and long‐term improvements in outcomes. Implementation of nutrition interventions and provision of delivery platforms for hard‐to‐reach populations is also crucial (Black 2013). Disruption and displacement of populations in emergency situations (including conflicts and natural disaster) pose an additional threat to the existing situation of undernutrition. Statistics suggest that women and children represent over three‐quarters of the estimated 80 million people in need of humanitarian assistance, and many countries with high maternal, newborn and child mortality rates are affected by humanitarian emergencies (UNICEF 2014).

Description of the intervention

Various interventions are recommended (or have been implemented) to improve maternal nutrition, including education, food provision and micronutrient supplements (iron, folic acid, multiple micronutrients) as well as other indirect interventions such as agricultural and financial interventions (Bhutta 2013). One of the nutritional interventions advocated to improve undernutrition in pregnant women is lipid‐based nutrient supplements (LNS). Adequate consumption of long‐chain, omega‐3 polyunsaturated fatty acids in the diet of pregnant women is essential, particularly the most biologically active forms (docosahexaenoic acid and eicosapentaenoic acid) (Coletta 2010), as these fatty acids support fetal growth, especially the brain and eyes, and deficiency may be associated with visual deficit and suboptimal behavioural development. However, there is not enough evidence to support the routine use of marine oil or other prostaglandin precursor supplements during pregnancy to reduce the risk of pre‐eclampsia, preterm birth, LBW or SGA (Makrides 2006).

LNS are a family of products designed to deliver nutrients to vulnerable people. There is no standard composition of LNS; however, most of the energy is supplied from fats. Three main LNS products are currently used in maternal and child nutrition: ready to‐use therapeutic foods (RUTF) or large‐quantity (LQ) LNS; ready‐to‐use supplementary foods (RUSF) or medium‐quantity (MQ) LNS; and LNS for home fortification or small‐quantity (SQ) LNS (Arimond 2015). RUTF or LQ‐LNS are designed for treatment of severe acute malnutrition, provide almost all energy requirements, and are given in large daily doses (Diop 2003); RUSF or MQ‐LNS are designed for treatment of moderate acute malnutrition and provide 50% to 100% of energy needed; while SQ‐LNS products are designed to prevent undernutrition and promote growth and development through home fortification of the local diet, and they provide less than 50% of the energy needed (Arimond 2015).

LNS provide a range of vitamins and minerals, but unlike most other micronutrient supplements they also provide energy, protein and essential fatty acids (Chaparro 2010). They are considered 'lipid‐based' because most of the energy provided by these products is from lipids (fats). There is no recommended composition for LNS, so existing projects have used different composition mixes. LNS recipes can include a variety of ingredients, but they typically include vegetable fat, peanut or groundnut paste, milk powder and sugar; other ingredients include whey, soy protein isolate, and sesame, cashew and chickpea paste (iLiNS Project 2016). Various commercial and locally available products are being used as LNS; however, researchers are exploring alternative recipes and formulations in efforts to develop affordable and culturally acceptable products for a range of settings. Similar products combining vegetable oil, groundnut paste, milk, sugar and micronutrients are being used as RUTF for managing both moderate and severe acute malnutrition in infants and children (WHO 2012; WHO 2013). Some studies have evaluated the feasibility and acceptability of LNS, suggesting that it is acceptable to infants as well as pregnant and lactating women (Adu‐Afarwuah 2011). Corn soy blends are different from LNS, as these are fortified blended foods (FBF) used as complementary foods or as supplementary foods for pregnant women.

LNS can be used as point‐of‐use food fortification or can be consumed directly during pregnancy as a source of energy, as protein and micronutrients in public health programmes, and as an intervention to improve birth weight and other pregnancy outcomes in areas where maternal undernutrition is prevalent (Arimond 2015; iLiNS Project 2016). These are usually given at a daily dose of less than 120 kcal/day. The doses and formulations of LNS can be modified according to the needs of the specific target group, and to date, there is no widely accepted, standard formulation for women during pregnancy. Some of the advantages of LNS are that they are ready‐to‐eat (no cooking required) and can be stored for as long as 18 to 24 months even in hot climates (Phuka 2008). This makes LNS especially useful in emergency settings where safe water and hygiene are common issues.

How the intervention might work

Ready‐to‐use lipid‐based nutrients could be a good source of macro‐ and micronutrients in a highly nutrient‐dense supplement, and they could be used as a dietary supplement to address the nutrient requirements of undernourished populations of pregnant women. The supplement composition can be tailored to meet the nutritional requirements of the target population. Cost is an important consideration but should be weighed against the effectiveness in maintaining and improving nutritional outcomes (Chaparro 2010).

Multiple studies have evaluated the impact of LNS when given to pregnant women and children in LMICs. The use of LNS has been associated with improved nutritional status among pregnant women and thereby improved growth and development outcomes among infants and children (Arimond 2015; Iannotti 2014; Thakwalakwa 2010), mainly by focusing on promotion of fetal growth during pregnancy through maternal supplementation. Cord leptin, produced by fetal adipocytes and placenta, has been positively associated with birth size and fetal fat mass (Clapp 1998; Forhead 2009; Lepercq 2001). Some authors hypothesise that LNS increases birth size, possibly through a change in the endocrine regulation of fetal development, and it is associated with higher cord blood leptin in primigravidae and women from the highest BMI tertile (Huybregts 2013). One study suggested that the initial effects of LNS are not sustained during infancy based on the hypothesis that fetuses adapted to better nutritional conditions in utero, which could have made them more sensitive to suboptimal nutritional and environmental factors during the postnatal period (Lanou 2014). One study from Malawi suggested that LNS did not influence the occurrence of maternal infections with Plasmodium falciparum parasitaemia, trichomoniasis or vaginal candidiasis, or of urinary tract infection (Nkhoma 2017). Other studies have suggested that LNS are palatable and acceptable to women in LMIC settings (Adu‐Afarwuah 2011; Mridha 2012; Mridha 2016a), although there were variances to adherence within the population (Harding 2014), as beneficiaries tended to make their own adaptations in terms of how much and how often to consume (Harding 2014). A study evaluating home delivery of LNS products in rural Malawi suggested that the cost of procurement, storage and weekly home delivery of LNS was largely comparable to other product delivery mechanisms currently undertaken in the public sector; however, the study also suggested that the expected health and other benefits associated with each proposed intervention strategy should be compared to the costs to set priorities (Vosti 2015).

Why it is important to do this review

LNS are currently being used in programmes targeting pregnant women in LMICs like Ghana, Malawi and Burkina Faso, with the expectation of improving birth outcomes and reducing LBW (Schofield 2009; WHO 2007). Current studies have shown mixed effects of this intervention using varying compositions, doses, frequencies and comparison groups between studies. Various types of fortified foods are currently in use, including FBF, complementary food supplements and multiple micronutrient powders (MNPs). The type and amount of nutrient varies according to the various products and formulations (Schofield 2009). This review will assess the effects and safety of LNS for women during pregnancy on maternal, birth and infant outcomes, as there is currently no systematic evaluation on this topic. The findings could inform policy and would be highly relevant for countries or areas that have a high burden of undernutrition or those facing emergency situations. We will attempt to assess the appropriate composition, frequency and duration of this intervention through various subgroup analyses. In addition, we will carry out a subgroup analysis on whether the pregnant women were identified and the LNS distributed through a facility or in a community. We are also developing a companion review to assess the effectiveness of preventive LNS plus complementary foods for health, nutrition and developmental outcomes in non‐hospitalised infants and children aged 6 to 23 months (Das in press). Together, these reviews will inform policy decisions on the effectiveness and safety of LNS compared to other interventions, and to assess which delivery platforms are effective.

Multiple micronutrient supplements and powders are currently not recommended for pregnant women (WHO 2016), but we will compare them to the provision of LNS, given the assumption that other micronutrients contained in the micronutrient powders could have an impact on pregnancy, birth and infant developmental outcomes; for example, zinc on preterm births (Ota 2015a). We will also compare LNS to antenatal nutrition education, since nutrition education conducted during the antenatal period with the aim of increasing energy and protein intake appears to be effective in reducing the risk of preterm birth and LBW, increasing head circumference at birth, increasing birth weight among undernourished women, and increasing protein intake (Ota 2015b).