INTRODUCTION — Undernutrition in pregnancy can be defined as a maternal nutritional state in which nutrient stores and macronutrient/micronutrient intake are less than that needed to achieve optimal maternal, fetal, and newborn outcomes. It is also a risk factor for development of adverse outcomes. Thus, identification and management of maternal undernutrition is important.
This topic will discuss issues related to both macronutrient and micronutrient deficiencies common to pregnancies in resource-limited settings. General issues regarding nutrition in pregnancy and issues related to malnutrition in children in resource-limited areas are reviewed separately:
●(See "Nutrition in pregnancy: Dietary requirements and supplements".)
●(See "Malnutrition in children in resource-limited settings: Clinical assessment".)
●(See "Management of moderate acute malnutrition in children in resource-limited settings".)
●(See "Management of uncomplicated severe acute malnutrition in children in resource-limited settings".)
●(See "Management of complicated severe acute malnutrition in children in resource-limited settings".)
CONSEQUENCES OF MATERNAL UNDERNUTRITION — The majority of direct experimental evidence regarding effects of maternal undernutrition on offspring development is derived from animal studies, given the ethical concerns of conducting this research in humans [1,2]. However, some data from human epidemiologic studies are available and show that, in general, maternal undernutrition impairs placental development, including a reduction in placental size, alterations in histomorphology, and reduction of blood flow, which can diminish nutrient delivery to the fetus [3]. In addition to fetal growth restriction, maternal undernutrition has been associated with low birth weight (LBW) and preterm birth and, in turn, the short- and long-term complications associated with these outcomes, and with maternal complications, such as life-threatening hemorrhage [4-7]. A systematic review noted a potential link between maternal nutrition, offspring telomere length, and preterm birth [8]. (See "Fetal growth restriction (FGR) and small for gestational age (SGA) newborns" and "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality" and "Overview of short-term complications in preterm infants" and "Overview of the long-term complications of preterm birth".)
The Barker hypothesis postulates that undernutrition during critical periods of pregnancy alters fetal morphology and physiology in permanent ways ("fetal programming") [9,10]. While these alterations provide short-term advantages to survival in utero, they restrict the individual's ability to adapt to a different environment after birth. The hypothesis is supported by numerous epidemiologic studies of populations that have experienced famine during pregnancy and reported offspring of such pregnancies are at increased risk for ischemic heart disease and related disorders in adult life [11-13]. (See "Fetal growth restriction (FGR) and small for gestational age (SGA) newborns", section on 'Impact on health status in adulthood'.)
The processes by which maternal undernutrition exerts fetal effects are not strictly caloric; they may also involve scarcities of specific micronutrients at critical stages in embryonic and fetal development [14]. However, many of these specific micronutrient deficiencies can be mitigated by supplementation.
For example:
●Vitamin A deficiency may cause night blindness, and supplementation of vitamin A is recommended by the World Health Organization (WHO) in areas where ≥5 percent of females have a history of night blindness in their most recent pregnancy or if ≥20 percent of pregnant people have a serum retinol level <0.70 micromol/L [15]. Vitamin A supplementation does not reduce perinatal or maternal mortality [16]. (See "Overview of vitamin A".)
●Calcium deficiency has been associated with hypertension and preterm birth, and high-dose calcium supplementation (>1 gram/day) in pregnant people with low-calcium diets has been associated with reduced risk of preeclampsia and preterm birth [17]. (See 'Calcium' below and "Preeclampsia: Prevention", section on 'Calcium supplementation when baseline dietary calcium intake is low'.)
●Zinc deficiency has been associated with LBW, preterm birth, and postpartum hemorrhage related to atony [18,19]. Although a Cochrane review reported a 14 percent relative reduction in preterm birth for patients receiving zinc supplementation compared with placebo in low-income settings and areas of high perinatal mortality [20], the WHO only recommends zinc supplementation in research settings [15].
●Iron deficiency anemia during pregnancy may be attributed to poor dietary intake of iron, inadequate iron absorption, and blood loss from intestinal helminths or malaria [21]. Iron supplementation reduces the frequency of maternal anemia and may have other fetal/neonatal benefits as well. (See 'Iron and folic acid' below and "Anemia in pregnancy", section on 'Iron deficiency'.)
●Folate deficiency increases the risk for neural tube defects, and periconceptional folic acid supplementation decreases the occurrence and recurrence of these defects. Supplementation also reduces the maternal risk of developing anemia since the increase in red blood cell production during pregnancy creates an increased demand for folate. (See "Preconception and prenatal folic acid supplementation" and "Maternal adaptations to pregnancy: Hematologic changes".)
●Iodine deficiency has potentially harmful effects, such as maternal and fetal/neonatal hypothyroidism. Low iodine intake can occur in areas where non-iodized salt and seafood low in iodine are consumed. (See "Nutrition in pregnancy: Dietary requirements and supplements", section on 'Iodine'.)
EPIDEMIOLOGY — Undernutrition in pregnancy remains a significant problem throughout low- and middle-income countries (LMICs). Rates of underweight pregnant people are up to 10 times higher in the poorest countries when compared with the richest countries [22]. The United Nations Children's Fund (UNICEF) 2018 Global Nutrition Report noted that 9.7 percent of pregnant people were underweight as defined by body mass index [23]. A 2019 meta-analysis estimated maternal undernutrition affected up to 23.5 percent of pregnant people in sub-Saharan Africa [24]. Since 2000, the overall rate has declined only slightly, and the rate in adolescent females has increased. A 2021 analysis of trends of low BMI among young and adult females in 40 LMICs reported that the prevalence decreased among adults but remained unchanged among 15 to 19 year olds [25].
Undernutrition is commonly associated with both being underweight and inadequate gestational weight gain. In a meta-analysis of studies from sub-Saharan Africa, up to 20 percent of pregnant people were underweight, and gestational weight gain was inadequate in 67 to 98 percent of these individuals [26].
RISK FACTORS
●Adolescents are at high risk for nutritional depletion as the mother and fetus are competing for nutrients to support adequate growth and development [27]. Many adolescents in resource-limited settings have inadequate nutrient reserves elevating their risk for adverse outcomes [28]. In addition, they may have low nutritional knowledge and poor understanding of severity of the condition [29] and may be less responsive to nutritional interventions than older pregnant people [30]. Adolescent pregnancy and nutritional status may be associated with early child wasting and underweight in their offspring, resulting in an intergenerational cycle of malnutrition [31]. The optimal strategies for managing pregnant adolescents with undernutrition require further study and may include increased ration provision.
●Patients carrying twins or higher order multiple gestations have higher nutritional requirements than those carrying singleton pregnancies. The higher caloric and micronutrient requirements place them at an up to twofold higher risk for developing undernutrition and micronutrient deficiencies [24]. As an example, the maternal basal metabolic rate in twin pregnancies increases approximately 10 percent above that in singleton pregnancies [32].
●Food insecurity is an established risk factor for undernutrition at all life stages, including pregnancy. Food insecurity has increased since 2014, with the sharpest increase in 2020 [33]. The Food and Agriculture Organization of the United Nations (FAO) estimates that nearly 12 percent of the world's population (928 million people) is exposed to severe food insecurity, with the prevalence of moderate or severe food insecurity 10 percent higher among females than among males [33].
●Residing in rural areas confers a 2.6-fold higher risk of undernutrition in pregnancy [24]. This may be due to less access to health care and nutritious foods in rural compared with urban areas.
NUTRITIONAL REQUIREMENTS DURING PREGNANCY
General dietary recommendations — Pregnancy is a time of increased nutritional requirements. For example, caloric requirements are increased by 340 to 450 kcal/day during the second and third trimesters and there are increased requirements for some micronutrients. General nutritional requirements during pregnancy are discussed in detail separately. (See "Nutrition in pregnancy: Dietary requirements and supplements".)
Recommendations for underweight patients — There are no formal dietary recommendations available for pregnant patients with undernutrition, regardless of country of residence. Most intake recommendations are based on the National Academy of Medicine (formerly the Institute of Medicine [IOM]) report on nutrition during pregnancy [34] and report on weight gain during pregnancy [4].
Although recommended dietary allowances have been developed by the National Academy of Medicine and are often used as a guide for dietary intake in the United States and Canada [35-38] (see "Nutrition in pregnancy: Dietary requirements and supplements"), these recommendations may not apply to patients who have preexisting micronutrient deficiencies and who require extra supplementation to recover. The World Health Organization (WHO), United Nations Children's Fund (UNICEF), and World Food Programme (WFP) have developed recommendations for micronutrient supplementation in low-income and emergency settings [39,40]. The recommended values of each micronutrient are shown in the table (table 1).
Clinical signs of micronutrient deficiencies are often nonspecific and may not be identified until whole body stores are severely depleted. This has been referred to as "hidden hunger" and affects up to two billion of the world's population, with high prevalence among pregnant people [41,42]. The most common micronutrient deficiencies are for iron, vitamin A, calcium, and zinc. For example, up to 40 percent of pregnant people in resource-limited settings suffer from anemia [43], and iron deficiency may account for up to 50 percent of global cases of anemia [44]. Vitamin A deficiency is estimated to affect 9.8 million pregnant people and 15.3 percent of pregnant people in at-risk populations [45].
EVALUATION FOR UNDERNUTRITION — An important component of routine prenatal care for all pregnant patients is a thorough, context-specific nutritional assessment [15]. (See "Prenatal care: Initial assessment" and "Prenatal care: Second and third trimesters".)
Dietary evaluation — A thorough evaluation of dietary intake and diversity is warranted in all pregnant patients. There are a number of approaches to this assessment, including 24-hour dietary recall, food diary, and food frequency questionnaires, which are discussed in detail separately (see "Dietary assessment in adults"). The minimum dietary diversity for women of reproductive age (MDD-W) is another approach that measures women's dietary diversity via a survey for 10 food groups [46,47]. It is a good predictor of micronutrient status in pregnant individuals in low- and middle-income countries (LMICs) [48].
Assessment of food security — Assessment of food security using standard tools is recommended. The Household Food Insecurity Access Scale (HFIAS) is a nine question tool validated across multiple settings that can be used for screening in pregnant patients (table 2) [49].
Physical examination — An anthropometric assessment should be performed at each prenatal visit. This includes review of baseline height, prepregnancy weight and body mass index (BMI), current weight and BMI, and mid-upper arm circumference (MUAC). (See 'Anthropometric diagnosis of undernutrition' below.)
In addition, undernourished patients should be evaluated for clinical instability, which may include hypotension, hypothermia, tachycardia, tachypnea, and inability to eat food. Any patient identified as unstable should be referred for inpatient evaluation and management.
Evaluation for physical signs and symptoms of micronutrient deficiencies is required as many of these individuals will have multiple micronutrient deficiencies (table 3).
Anthropometric diagnosis of undernutrition
Mid-upper arm circumference — A MUAC <23 cm is a reasonable threshold to identify maternal undernutrition as it is reproducible, reflects maternal fat stores and lean mass, correlates strongly with low BMI [50-52], and predicts the risk of delivering a low birth weight (LBW) infant [50,52-54]. A meta-analysis of anthropometric indicators for acute malnutrition associated with adverse birth outcomes in humanitarian conflict zones concluded MUAC is the preferred indicator because of a relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings), and prior knowledge of gestational age is unnecessary [50].
Further research is needed to determine if MUAC cutoff values should differ between different geographic regions, but available data suggest a MUAC <23 cm can be applied worldwide [55]. The Sphere guidelines recommend using a MUAC cutoff range of 21 to 23 cm for maternal enrollment into supplementary feeding programs, and MUAC <21 cm in humanitarian emergencies when resources are severely limited [56]. Some countries have guidelines for the appropriate MUAC cutoff in various clinical settings, and these should be consulted where available.
The World Health Organization (WHO) does not have standard recommendations regarding MUAC use during pregnancy, but the United Nations Children's Fund (UNICEF) and several other international organizations use it as a screening tool for children.
Low body mass index — Some programs use a BMI cutoff of 18.5 kg/m2 for undernutrition as <18.5 kg/m2 is considered underweight for a nonpregnant female [57] and, in pregnancy, associated with an increased risk for LBW [58] and preterm birth [59]. A BMI of 16 to 18.49 kg/m2 is considered moderate undernutrition; a BMI <16.0 kg/m2 is considered severe undernutrition and has a particularly high risk for LBW and preterm birth. However, a meta-analysis of anthropometric indicators for acute malnutrition associated with adverse birth outcomes in humanitarian conflict zones found that data were insufficient to establish a narrow range of BMI cut-off points by gestational age for identifying pregnant individuals at increased risk for LBW [50].
Of note, although BMI is readily determined in resource-rich countries, the staff in many resource-limited countries may have difficulty determining BMI compared with MUAC.
Other approaches
●Low gestational weight gain — Specific guidelines for appropriate gestational weight gain have been published by the National Academy of Medicine (formerly the Institute of Medicine [IOM]). Over the course of a term pregnancy, gestational weight gain below the levels recommended by these guidelines (table 4) increases the risk for small for gestational age (SGA) infants [60,61]. When considered in terms of weekly maternal weight gain, weight gain <300 grams/week correlates with an increased risk of LBW [50]. The LifeCycle Project-Maternal Obesity and Childhood Outcomes Study Group has published slightly different appropriate gestational weight gain ranges, with adjustments that account for preeclampsia, gestational diabetes, and different degrees of obesity. (See "Gestational weight gain", section on '2009 IOM weight gain recommendations' and "Gestational weight gain", section on 'Subsequent data that may inform guidance for gestational weight gain'.)
Specific recommendations are needed for appropriate gestational weight gain in Asian populations [62] as they are more likely to be classified as having inadequate gestational weight gain when universal criteria are applied.
●Maternal weight for gestational age — There is no clear cutoff value for maternal weight for gestational as a screening tool to predict LBW, but <45 kg at any gestational age suggests a high risk of LBW in Asian countries and could be used as an enrollment criterion in feeding programs [50].
Maternal weight for gestational age Z-score charts are available and have been proposed as a new tool to more accurately predict needed weight gain in underweight patients [63-65]. Undernutrition is defined as a weight for gestational age Z-score more than two standard deviations below the mean. However, in resource-limited settings, an accurate estimate of gestational age is often not possible, making this measurement difficult to implement effectively.
Laboratory examination — Prenatal laboratory examination is guided by local and national recommendations and available resources. Other laboratory tests are ordered based on suspicious clinical findings rather than undernutrition alone. (See "Prenatal care: Initial assessment", section on 'Laboratory tests' and "Prenatal care: Second and third trimesters".)
TREATMENT OF UNDERNUTRITION
Basic principles — Pregnant patients identified as undernourished should receive nutritional education about selecting and increasing intake of energy-dense, locally available foods, when food is secure and available [15]. Educational programs may include recipes for these foods. This educational approach has been demonstrated to be effective in increasing protein intake and reducing the risk of preterm birth and low birth weight (LBW) [66,67]. A systematic review of the effects of nutritional counseling on maternal and infant outcomes in low- and middle-income countries (LMICs) demonstrated improved caloric and protein intake, improved gestational weight gain, and initiation of breastfeeding after giving birth [68]. Design of educational programs varies widely, and further research is required to identify optimal design and outcome assessment.
Use and types of supplements — Provision of supplementation should begin in the preconception period or as early in pregnancy as possible to maximize maternal and neonatal benefits [69].
If locally available foods are not sufficient to correct undernutrition, which is common in resource-limited settings, then specially formulated products, including multiple micronutrient supplements (MMNs), fortified blended flours, or lipid-based nutrient supplements (LNS), may be used to address both macronutrient and micronutrient deficiencies [39]. Micronutrient supplements should be used in conjunction with locally available, nutrient-dense foods or with balanced energy and protein supplements to provide required macronutrients. Choice of supplement is largely based on product availability.
Balanced energy and protein supplementation — Balanced energy and protein supplements are generally considered to be those products that provide less than 25 percent of energy from protein. The World Health Organization (WHO) recommends them for pregnant people with undernutrition [15] based on evidence of a possible modest reduction in the rates of stillbirth and small for gestational age infant (SGA) in a meta-analysis of randomized trials (stillbirth: risk ratio [RR] 0.60, 95% CI 0.39-0.94; SGA: RR 0.79, 95% CI 0.69-0.90) [66]. The same meta-analysis did not support use of high-protein supplementation; thus, high-protein supplements are not recommended to improve birth outcomes [15]. A subsequent systematic review of studies conducted in low- and middle-income countries (LMICs) also found that balanced energy and protein supplementation reduced the incidence of stillbirth (RR 0.39, 95% CI 0.19-0.80) and LBW (RR 0.60, 95% CI 0.41-0.86) [70].
The types of foods used to deliver balanced protein and energy supplementation are diverse and include beverages, biscuits, milk products, and enriched breads [71]. Commercially available products include high-energy biscuits and fortified spreads. The nutrient content of these products is summarized in the table (table 5). The type and amount of supplement should be chosen based on local availability of products, acceptability of the product among the target population, and the nutrient deficiency targeted [15]. Many balanced protein and energy supplements have been developed for local use and are not commercially available.
Fortified blended flours — Fortified blended flour products are designed to provide 10 to 15 percent of energy from protein, 20 to 25 percent of energy from fat, and two-thirds of the daily requirements for micronutrients [72]. Several fortified blended flour products are available for the treatment of undernutrition [73]. Most were developed for use in infants and children but can be used for supplemental nutrition in pregnancy in appropriate contexts [39]. Use of a fortified flour blend in pregnancy has been associated with reductions in both maternal anemia and preterm birth [74] and increased birth weight [75].
Super Cereal is the fortified blended flour product recommended by the World Food Programme (WFP) and the United States Agency for International Development (USAID). Several formulations of Super Cereal are available and include a grain product of corn, wheat, or rice added to soya, with vitamin and mineral fortification. Corn-soya blended flour is the most widely used for undernourished pregnant people; however, rice-soya and wheat-soya are appropriate products if more acceptable to the target population. Locally produced fortified blended flours have also been developed for use in a number of countries. Most of these products are based on the Super Cereal formulation but with alterations in the grain components to utilize locally available ingredients. The nutrient composition of Super Cereal is shown in the table (table 6).
The WFP and USAID recommend a ration of 200 to 250 grams of Super Cereal mixed with 25 grams of oil daily. This 250 gram ration includes provision for sharing [76]. The product is prepared as a porridge or gruel by mixing 40 grams of flour with 250 mL of clean water and simmering for 5 to 10 minutes.
Some negative aspects of fortified blended flours is that they require cooking and teaching of proper preparation of the product. Preparation requires the use of clean boiling water, which increases the time burden on the individual. Contamination of the product can occur during the cooking process, and it can spoil if not consumed within a few hours of preparation. Additionally, most flour products have lower energy density than lipid-based supplements, so they require larger amounts to be ingested to meet caloric needs. On the other hand, fortified blended flours are often similar to locally consumed foods and thus largely acceptable for consumption in target populations.
Lipid-based nutrient supplements — LNS are designed to deliver a food-safe, standard amount of calories and nutrients to individuals with undernutrition. A 2018 meta-analysis of four randomized trials of the use of LNS for the treatment of undernutrition in pregnancy identified a small benefit in infant weight and length compared with traditional iron-folic acid supplementation and/or MMNs [77]. No trials using LNS in emergency settings were available at the time of the review. In a subsequent meta-analysis of 11 randomized trials, LNS use during pregnancy significantly reduced the risks of LBW, SGA, and stunting compared with fortified corn-soya blend, iron-folic acid, and/or MMNs [78].
The majority of energy in LNS is provided by lipids, but the quantity of LNS prescribed varies among products and may be small (SQ-LNS), medium (MQ-LNS), or large (LQ-LNS). LQ-LNS are designed for treatment of severe undernutrition, while MQ-LNS are designed for treatment of moderate undernutrition. SQ-LNS have been used for the prevention rather than the treatment of undernutrition as they provide the majority of micronutrient requirements but only a fraction of daily caloric needs [79,80].
LNS products provide protein, lipids, fatty acids, and multiple micronutrients. The composition of these products varies but typically includes vegetable oil, peanut (groundnut) paste, milk powder, sugar, and micronutrients and vitamins. There is no standard composition for use in pregnant people, although many programs have designed them to meet the micronutrient needs required during pregnancy [79,81-84]. Commercial products are also available (table 7).
No standardized international guidance is available on dosing; most programs employ a daily ration of ready-to-use supplementary foods to provide an additional 118 to 1000 kcal [79,81-83,85]. Higher dose supplementation does not appear to be superior to lower dose rations. As there is no consensus on dosing and no clear evidence to support one regimen over another, we recommend rations of one to two sachets of LNS (providing 500 to 1000 kcal) daily as this may be the easiest to deliver operationally.
Multiple micronutrient supplements — Micronutrient deficiencies are common among pregnant people in resource-limited settings. MMNs are point-of-use fortification packets formulated to deliver standard concentrations of common micronutrients. They can reduce deficiencies but may not eliminate them [86]. The United Nations International Multiple Micronutrient Preparation (UNIMMAP) is a commonly recommended composition (table 8) [87].
In a 2019 meta-analysis of randomized trials in pregnancy comparing MMNs with supplements of iron with or without folic acid, MMNs reduced the risk for LBW (187 versus 212 per 1000, RR 0.88, 95% CI 0.85-0.91) and SGA (310 versus 337 per 1000, RR 0.92, 95% CI 0.88-0.97) [88]. Risks for preterm birth and perinatal mortality were similar in both groups. After restricting analysis to trials including gestational age assessment, a 2023 meta-analysis continued to demonstrate that MMN probably reduced the risk of LBW (RR 0.87, 95% CI 0.78-0.97), preterm birth (RR 0.90, 95% CI 0.79-1.03), and SGA (RR 0.90, 95% CI 0.83-0.99) [89]. Long-term trials have found that MMNs consumed during pregnancy also have benefits extending into early childhood, such as improved body weight, mid-upper arm circumference, head circumference [90], and enhanced infant antibody responses to the diphtheria-tetanus-pertussis (DTP) vaccine [91].
WHO guidelines recommend use of MMNs in pregnant people receiving antenatal care in any health care facility or community-based setting, in the context of rigorous research [92]. The evidence for this recommendation was mainly derived from LMICs, thus they state that applicability to high-income countries or to populations not at risk of micronutrient (eg, adequate diet, food fortification programs) is unclear. Subsequently, the NiPPeR trial evaluated multiple-micronutrient supplementation with optimized riboflavin, vitamin B6, vitamin B12, and vitamin D to individuals of childbearing age in three high-income countries (United Kingdom, Singapore, New Zealand) [93]. Key findings were that over 90 percent of participants had inadequate concentrations of one or more of the micronutrients at the start of trial and that supplementation improved micronutrient levels in pregnancy and during lactation.
Other supplements
Iron and folic acid — The WHO recommends daily iron and folic acid supplementation with 30 to 60 mg of elemental iron and 400 micrograms of folic acid [15] or once weekly supplementation with 120 mg of elemental iron and 2800 micrograms of folic acid for pregnant people [15]. Alternate-day iron dosing is becoming more common since less frequent dosing reduces adverse effects and improves iron uptake. In a systematic review of periconception interventions in LMICs, iron plus folic acid supplementation reduced the risk of anemia, and folic acid supplementation reduced the risk of neural tube defects [94]. Folic acid has also been associated with increased birth weight and decreased incidence of LBW and SGA [95,96]. (See "Anemia in pregnancy", section on 'Prevention of iron deficiency' and "Preconception and prenatal folic acid supplementation", section on 'Administration'.)
Calcium — The WHO recommends 1.5 to 2 grams oral elemental calcium daily for pregnant people in populations with low dietary calcium intake to reduce the risk of preeclampsia [15,39]. Calcium supplementation at doses >1 gram/day has been associated with a reduced risk of preterm birth [67], likely related to the reduced risk of preeclampsia. (See "Preeclampsia: Prevention", section on 'Calcium supplementation when baseline dietary calcium intake is low'.)
Iodine — The WHO and United Nations Children's Fund (UNICEF) recommend iodine supplementation (250 micrograms daily) for pregnant people in countries where less than 20 percent of households have access to iodized salt [15]. (See "Nutrition in pregnancy: Dietary requirements and supplements", section on 'Iodine'.)
Vitamin A — The WHO recommends vitamin A supplementation in areas where ≥5 percent of females had a history of night blindness in their most recent pregnancy or where ≥20 percent of pregnant people have a serum retinol level <0.7 micromol/L [15]. The recommended dose is 10,000 international units daily or 25,000 international units weekly for a minimum of 12 weeks during pregnancy [15]. Vitamin A supplementation in combination with other micronutrients may decrease the risk of LBW [67].
Vitamins and other substances that do not need to be supplemented — The WHO does not recommend supplementation of vitamins B6, C, D, and E in pregnancy [15,97]. Although deficiencies can have health consequences, there is no evidence to support a benefit of routine use of any of these supplements. (See "Vitamin D and extraskeletal health", section on 'Pregnancy outcomes'.)
L-arginine — L-arginine is an essential amino acid and precursor to nitric oxide with roles in vascular development and fetal growth. Studies of oral low-dose supplementation in pregnancy have reported potential favorable effects for reducing the incidence of preeclampsia and improving birth outcomes, including higher birth weight, longer gestation, and less respiratory distress syndrome [98-100]. L-arginine has been safely administered in pregnancy in several clinical trials but additional research is needed to confirm its effectiveness before widespread adoption of the intervention.
In addition, the optimal dosing strategy is not well established for use in pregnancy. There is no established guideline for maximum intake of L-arginine. Typical diets in high-income Western settings include 4 to 5 g/day of arginine [101]. Arginine administration appears to be safe up to 20 to 30 g/day [102,103]. Higher doses (>9 g) are associated with increased adverse gastrointestinal symptoms [104]. Trials in pregnancy have included doses ranging from 3 to 30 g/day for varying durations with higher doses typically being administered for shorter durations.
Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) — Randomized trials have suggested a possible lower risk for preterm birth and a lower risk of persistent wheeze or asthma in offspring of pregnant individuals receiving n-3 LCPUFA supplementation during pregnancy. These and other outcome data are reviewed in detail separately. (See "Fish consumption and marine omega-3 fatty acid supplementation in pregnancy".)
The WHO recommends further research prior to widespread implementation of n-3 LCPUFA supplementation [105].
Distribution — There are two main approaches to community feeding programs: blanket distribution and targeted distribution.
●Blanket distribution – Blanket distribution provides supplementary food to an entire at-risk population, such as all females of childbearing age or all pregnant and lactating people in a given region. This strategy often aims to prevent development or progression of acute malnutrition. The United Nations High Commissioner for Refugees (UNHCR) recommends implementation of blanket supplementary feeding programs when the rate of undernutrition is ≥15 percent in a population or 10 to 14 percent in a population with aggravating factors (table 9) [106]. However, this approach is often cost prohibitive because large populations of individuals without acute malnutrition will receive treatment, but it may be highly effective in emergency settings.
●Targeted distribution – Targeted distribution identifies individuals meeting criteria for admission into a feeding program and provides rations to these individuals. This approach seeks to treat existing acute malnutrition. Targeted supplementary feeding is recommended by the UNHCR when global acute malnutrition is 10 to 14 percent or 5 to 9 percent in a population with aggravating factors (table 9) [106].
Adjunctive therapies — Pregnant individuals with undernutrition are at increased risk of infection and inflammation, which can lead to preterm birth, thus use of anti-infection therapies can improve pregnancy and newborn outcome.
●Prevention of malaria by mosquito avoidance and intermittent preventive treatment in pregnancy (IPTp) and treatment of malarial infection are established components of prenatal care in areas where malaria is endemic. (See "Malaria in pregnancy: Prevention and treatment".)
●Empiric anthelmintic treatment is a component of strategies to improve maternal nutrition in areas where helminths are endemic and anemia is prevalent [107-109]. Albendazole treats common helminth infections; reduces the frequency of anemia in pregnancy, especially when added to iron supplementation; and appears to be safe when administered after the first trimester [109]. Additionally, antenatal treatment may improve postnatal outcome as infections during pregnancy have been associated with lower cognitive and gross motor functioning in offspring [110]. There is limited information on fetal effects of early pregnancy exposure, so use during the first trimester is not recommended. (See "Anthelminthic therapies", section on 'Albendazole'.)
●Azithromycin is another empiric anti-infective prenatal treatment that has shown promising results for reducing low birth weight and infant death, but requires further study [111-116].
ASSESSING RESPONSE TO TREATMENT — Mid-upper arm circumference (MUAC), weight, and/or body mass index (BMI) should be measured at each prenatal visit to monitor for recovery, depending on which criteria were used to diagnose malnutrition and recovery. Additionally, gestational weight gain should be monitored closely and compared with existing guidelines, such as the widely used National Academy of Medicine (formerly the Institute of Medicine [IOM]) guideline (table 4) [117,118].
The National Academy of Medicine considers weekly maternal weight gain <230 grams as slow (below average) [4], which can be used as a criterion for gauging response to treatment.
When MUAC is used to identify malnourished patients needing supplementation, the United Nations High Commissioner for Refugees (UNHCR) suggests that supplemental feeding programs use MUAC ≥23 cm as the criterion for discharge from the feeding program [106]. When BMI is used as an entry criterion for a feeding program, a BMI >18.5 kg/m2 can be considered for discharge from the program. However, if resources allow, supplemental feeding should be continued until six months postpartum as nutrient demands remain high during this period of exclusive breastfeeding. A randomized trial of an LNS among pregnant individuals in Burkina Faso demonstrated that continued postpartum provision of LNS may modestly improve length-for-age z-score (LAZ) of offspring to age 12 months [119].
MANAGEMENT OF TREATMENT FAILURE — In most cases, therapy will be ineffective in alleviating undernutrition in pregnancy. For example, a trial of supplemental food (900 kcal/day and 33 to 36 grams of protein/day) for pregnant Malawian patients with moderate malnutrition (mean mid-upper arm circumference [MUAC] 22.3 cm) reported that mean MUAC did not increase by the end of the study and overall weight gain was modest [82]. The patients received a mean five rations of the supplemental food over a period of 11.4 weeks from enrollment until delivery. Additionally, in a secondary analysis of a randomized trial, pregnant adolescents had poorer response to nutritional interventions than adults >20 years old [30]. This may be attributable to increased nutritional needs of adolescents and nutritional competition, as well as social determinants of health among this population.
In cases of treatment failure, the clinician should reevaluate the patient, keeping in mind supplementary food is needed in wasting patients but may not be sufficient unless used in combination with other interventions:
●Reevaluate nutritional intake. Determine whether the patient is so poor that they have no other food. In such cases, the supplement is unlikely to be sufficient to help them recover and may need to be increased.
●Assess for nonadherence. Confirm consumption of the supplemental food as it may be voluntarily shared with others or sold, stolen, or controlled by family members, individuals residing with the patient, or community members rather than the beneficiary.
●Evaluate for an ongoing inflammatory process, such as an abscess, a chronic pelvic or bone infection, intestinal helminths, or a large burden of placental malaria. In settings where diagnostic capabilities are limited, it may be prudent to simply treat for malaria or sexually transmitted infections as they are so common. (See "Malaria in pregnancy: Prevention and treatment" and "Malaria in pregnancy: Epidemiology, clinical manifestations, diagnosis, and outcome".)
●Evaluate for a medical etiology of undernutrition. When a social etiology or inadequate nutritional intake is not identified, evaluation for HIV, tuberculosis, blood dyscrasias, malignancy, and other chronic conditions should be undertaken and may be facilitated by referral to an appropriate medical center with advanced diagnostic capabilities.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Nutrition and supplements in pregnancy" and "Society guideline links: Pediatric malnutrition".)
SUMMARY AND RECOMMENDATIONS
●Importance of adequate nutrition – Adequate maternal nutrient intake is required to promote optimal growth of the fetus and favorable outcomes for the mother and infant. Undernutrition during pregnancy can result in fetal growth restriction, preterm birth, and low birth weight infants. (See 'Consequences of maternal undernutrition' above.)
●Diagnosis of undernutrition – Undernutrition during pregnancy can be diagnosed based on a mid-upper arm circumference (MUAC) <23 cm, body mass index (BMI) <18.5 kg/m2, and/or gestational weight gain <230 grams/week. (See 'Anthropometric diagnosis of undernutrition' above.)
●Evaluation of undernourished patients – The work-up of undernourished pregnant patients should include an evaluation of dietary intake and diversity (eg, MDD-W), assessment of food insecurity, anthropometric assessment (eg, BMI, MUAC), evaluation for clinical instability, and examination for signs and symptoms of micronutrient deficiencies. The standard prenatal laboratory examination is based on local and national recommendations; additional laboratory tests are ordered based on suspicious clinical findings rather than undernutrition alone. (See 'Evaluation for undernutrition' above.)
●Treatment
•When food is secure and available, the initial treatment approach involves nutritional education on energy-dense, locally available foods. In endemic areas, empiric treatment of helminthic infection reduces the risk for anemia. (See 'Basic principles' above and 'Adjunctive therapies' above.)
•When locally available foods are not sufficient to correct undernutrition, then balanced energy and protein supplements such as lipid-based nutrient supplements, fortified blended flours, or multiple micronutrient supplements can be used to address both macronutrient and micronutrient deficiencies. (See 'Use and types of supplements' above.)
●Assessing response to treatment
•Response to treatment can be assessed by achievement of MUAC ≥23 cm, weight gain ≥230 grams/week, and/or BMI ≥18.5 kg/m2, depending on which criteria were used to diagnose undernutrition. If resources allow, supplemental feeding should be continued until six months postpartum as nutrient requirements remain high. (See 'Assessing response to treatment' above.)
•If recovery from undernutrition does not occur with treatment, dietary intake and use of supplemental food should be reassessed, and referral for in-depth work-up for underlying disease conditions should be undertaken. (See 'Management of treatment failure' above.)
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