Early Growth and Cognitive Development in Children Born Preterm: Relevance of Maternal Body Mass Index.

OBJECTIVE: Maternal prepregnancy body mass index (BMI) represents a surrogate marker of fetal exposures to the maternal metabolism during pregnancy. Yet, it remains poorly understood whether this marker indicates risk of altered trajectories in postnatal growth and development in children born preterm. This study aimed to determine whether maternal prepregnancy BMI is associated with altered growth and development in children born preterm. STUDY DESIGN: A retrospective cohort study evaluated prepregnancy BMI as the exposure for childhood outcomes using linear regression and mixed effects models. The 38 children included in this follow-up evaluation originally participated in a prospective, observational cohort study to determine longitudinal levels of lipid species in preterm human milk expressed by women who delivered prior to 32 weeks. Childhood outcomes in this study were anthropometric measures during hospitalization (n = 38), after discharge through 36 months (n = 34) and Bayley-III developmental scores through 18 months corrected age (n = 26). RESULTS: In 38 children born prior to 32 weeks, higher maternal prepregnancy BMI was independently associated with higher preterm infant growth velocity during hospitalization, but not associated with in-hospital change in length or head circumference and/or postdischarge growth. In univariate linear regression models, higher maternal BMI was associated with lower cognitive scores at 18 months corrected age. This significant association remained in an adjusted model accounting for relevant influences on early childhood development. CONCLUSION: Increasing maternal prepregnancy BMI may reflect risk of altered growth and cognitive development in children born preterm. KEY POINTS: · Maternal BMI was associated with early preterm infant weight gain.. · Maternal BMI was not associated with postdischarge growth.. · Increased maternal BMI may be associated with lower cognitive function scores in offspring..

Randomized Controlled Trial of Early Docosahexaenoic Acid and Arachidonic Acid Enteral Supplementation in Very Low Birth Weight Infants.

OBJECTIVE: To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation. STUDY DESIGN: This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks. RESULTS: Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003). CONCLUSIONS: Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03192839.

Considerations for Preterm Human Milk Feedings When Caring for Mothers Who Are Overweight or Obese.

BACKGROUND: Mother's milk is the recommended source of nutrition for all newborns. Preterm infants may be further compromised by maternal factors that impede successful lactation and alter milk composition. PURPOSE: To review and summarize the state of the science regarding implications of maternal overweight and obesity on successful lactation and associated alterations in preterm mother's milk composition. METHODS/SEARCH STRATEGY: PubMed, EMBASE, and Web of Science searches were performed using relevant key words to identify references addressing maternal overweight or obesity, prematurity, human milk, and lactation. FINDINGS/RESULTS: In the United States, more than half of women enter pregnancy with an overweight or obese body mass index. These women have increased risk of adverse pregnancy outcomes and obstetric complications that can undermine successful initiation and continuation of lactation, including preterm birth. Maternal overweight and obesity are also associated with alterations in mother's milk composition. IMPLICATIONS FOR PRACTICE: Mother-preterm infant dyads affected by maternal overweight and obesity are at risk for barriers to initiation and continuation of lactation. Support for early initiation of milk expression is needed. Continued support, especially during the first weeks of lactation, can facilitate sustained milk production. IMPLICATIONS FOR RESEARCH: Considerable knowledge gaps remain in this area of human milk science. Future research is needed to facilitate more comprehensive understanding of differences in milk composition associated with maternal overweight and obesity and their impact on clinical outcomes in the preterm infant.

Energy and Protein Intake During the Transition from Parenteral to Enteral Nutrition in Infants of Very Low Birth Weight.

OBJECTIVE: To evaluate the association between nutrition delivery practices and energy and protein intake during the transition from parenteral to enteral nutrition in infants of very low birth weight (VLBW). STUDY DESIGN: This was a retrospective analysis of 115 infants who were VLBW from a regional neonatal intensive care unit. Changes in energy and protein intake were estimated during transition phase 1 (0% enteral); phase 2 (>0, ≤33.3% enteral); phase 3 (>33.3, ≤66.7% enteral); phase 4 (>66.7, <100% enteral); and phase 5 (100% enteral). Associations between energy and protein intake were determined for each phase for parenteral nutrition, intravenous lipids, central line, feeding fortification, fluid restriction, and excess non-nutritive fluid intake. RESULTS: In phases 2 and 3, infants receiving feeding fortification received less protein than infants who were unfortified (-1.1 and -0.3 g/kg/d, respectively; P < .001). However, this negative association was not observed after adjusting for relevant nutrition delivery practices. Despite greater enteral protein intake during phases 2 and 3 (0.3 and 0.8 g/kg/d, respectively; P < .001), infants with early fortification received less parenteral protein than infants who were unfortified (-1.4 and -1.1 g/kg/d, respectively; P < .001). Similar patterns were observed for energy intake. Protein intake declined during phases 3 and 4. CONCLUSIONS: Infants paradoxically received less protein and energy on days with early fortification, suggesting that clinicians may lack easily accessible data to detect the association between nutrition delivery practices and overall nutrition in infants who are VLBW.

Nutritional Practices and Growth in Premature Infants After Surgical Necrotizing Enterocolitis.

OBJECTIVE: The aim of the study was to describe the nutritional provisions received by infants with surgical necrotizing enterocolitis (NEC) and the associated effects on short-term growth. METHODS: Through the Children's Hospitals Neonatal Database, we identified infants born ≤32 weeks' gestation with surgical NEC from 5 regional neonatal intensive care units for 4 years. Excluded infants had isolated intestinal perforation and died <14 days postoperatively. Infants were stratified by their median parenteral protein dose (low [LP] or high [HP] protein) for the first postoperative week. The primary outcome was postoperative weight growth velocity. Growth (weight, length, and head circumference [HC]) was measured and the effects related to protein dose were estimated using multivariable analyses. RESULTS: There were 103 infants included; the median parenteral protein dose received was 3.27 g ·â€Škg ·â€Šday (LP: 2.80 g ·â€Škg ·â€Šday; HP: 3.87 g ·â€Škg ·â€Šday). Postoperative weight (11.5 ±â€Š6.5 g ·â€Škg ·â€Šday) and linear growth (0.9 ±â€Š0.2 cm/wk) were similar regardless of dose (P > 0.3 between groups for weight and length). Unadjusted and independent associations were identified with HC changes and HP dose (ß = 0.1 cm/wk, P = 0.03) after adjusting for gestational age, the presence of severe bronchopulmonary dysplasia, short bowel syndrome, blood stream infection, severe intraventricular hemorrhage, small for gestational age, and calorie intake. Eventual nonsurvivors received 18% less protein and 14% fewer calories over the first postoperative month. CONCLUSIONS: Postoperative protein doses in infants with surgical NEC appear related to increases in HC. The influence of postoperative nutritional support on risk of adverse outcomes deserves further attention.

Growth and Development in Extremely Low Birth Weight Infants After the Introduction of Exclusive Human Milk Feedings.

Objective To estimate associations of exclusive human milk (EHM) feedings with growth and neurodevelopment through 18 months corrected age (CA) in extremely low birth weight (ELBW) infants. Study Design ELBW infants admitted from July 2011 to June 2013 who survived were reviewed. Infants managed from July 2011 to June 2012 were fed with bovine milk-based fortifiers and formula (BOV). Beginning in July 2012, initial feedings used a human milk-based fortifier to provide EHM feedings. Infants were grouped on the basis of feeding regimen. Primary outcomes were the Bayley-III cognitive scores at 6, 12, and 18 months and growth. Results Infants (n = 85; 46% received EHM) were born at 26 ± 1.9 weeks (p = 0.92 between groups) weighing 776 ± 139 g (p = 0.67 between groups). Cognitive domain scores were similar at 6 months (BOV: 96 ± 7; EHM: 95 ± 14; p = 0.70), 12 months (BOV: 97 ± 10; EHM: 98 ± 9; p = 0.86), and 18 months (BOV: 97 ± 16; EHM: 98 ± 14; p = 0.71) CA. Growth velocity prior to discharge (BOV: 12.1 ± 5.2 g/kg/day; EHM: 13.1 ± 4.0 g/kg/day; p = 0.33) and subsequent growth was similar between groups. Conclusion EHM feedings appear to support similar growth and neurodevelopment in ELBW infants as compared with feedings containing primarily bovine milk-based products.

Early docosahexaenoic and arachidonic acid supplementation in extremely-low-birth-weight infants.

BACKGROUND: Extremely-low-birth-weight (ELBW) infants accrue large deficits in docosahexaenoic acid (DHA) and arachidonic acid (ARA) and require improved supplementation strategies. We hypothesized that once daily DHA+ARA drops applied to buccal mucosa will increase blood levels. METHODS: Thirty ELBW infants were randomized to receive DHA 20 mg/kg/d + ARA 40 or 60 mg/kg/d + ARA 120 mg/kg/d or placebo within 72 h of age for 8 wk duration. Red blood cell phospholipid levels of DHA (primary) and ARA (secondary) were measured at 2 and 8 wk of age. RESULTS: Twenty-eight survivors with a median birth weight of 806 g completed dosing and sampling. Red blood cell levels were similar between the three groups at 2 wk (DHA: 4.62 wt% (interquartile range (IQR) 4.1-5.5) for all, P = 0.29 between groups; ARA: 21.1 wt% (IQR 18.78-22.6) for all, P = 0.41 between groups) and 8 wk (DHA: 6.0 wt% (IQR 5.1-7.1) for all, P = 0.57 between groups; ARA: 20.1 wt% (IQR 18.3-23.1) for all, P = 0.63 between groups). DHA in all infants showed a median increase of 31% from 2 to 8 wk (P < 0.04). ARA levels did not significantly change over time (P > 0.6). CONCLUSION: Daily buccal DHA and ARA supplements did not affect fatty acid levels in ELBW infants.

Linking fat intake, the intestinal microbiome, and necrotizing enterocolitis in premature infants.

Components of diet, including the total amounts and specific types of fat, affect the composition of the intestinal microbiome in both animal models and cohort studies of humans. Amounts of total fat and specific fatty acids (FA) are some of the most variable nutritional components of breast milk. Evaluations of the microbiome in premature infants have shown decreased diversity of species and increased proportions of potentially pathogenic bacteria. Microbial patterns in premature infants may be affected by nutritional fat intake, altering risk of diseases such as necrotizing enterocolitis. Dietary FA may also impact disease susceptibility through molecular mechanisms. Specifically, intestinal Toll-like receptor 4 expression is altered by manipulation of FA in murine models. Abnormal increased expression of Toll-like receptor 4, the receptor for lipopolysaccharide, has been implicated in necrotizing enterocolitis. This report will review the role of dietary fat in the composition of the intestinal microbiome, the extreme variability of FA intake in premature infants, and associations of both dysbiosis and FA intake with the development of necrotizing enterocolitis.

Parenteral nutrition use and associated outcomes in a select cohort of low birth weight neonates.

OBJECTIVE: The aim of this study is to assess the influence of parenteral nutrition (PN) on the time to regain birth weight in premature neonates born between 1,500 and 2,499 g. STUDY DESIGN: A retrospective analysis stratified premature neonates born between 1,500 and 2,499 g by receipt of PN or intravenous dextrose at ≤ 72 hours of age. The primary outcome was the time to regain birth weight. Secondary measures included preterm-associated morbidities, time to achieve predefined enteral nutrition milestones, and length of stay. Multivariable regression estimated associations between PN and time to achieve nutrition milestones. RESULTS: Among 260 eligible neonates, those receiving PN (53%) were less mature, weighed less at birth, had a higher index of illness severity, and higher prevalence of preterm-associated morbidities (p < 0.01). The time to regain birth weight (PN, 9.4 ± 3.5 d; no PN, 9.5 ± 3.4 d) was similar between groups. Regression analysis adjusting for gestational age, illness severity, and sepsis demonstrated that PN exposure was associated with a greater time to achieve nutrition milestones and length of stay (p < 0.05). CONCLUSION: Although its impact on growth remains uncertain among premature neonates born between 1,500 and 2,499 g, PN was independently associated with a greater time to achieve nutrition milestones.

Targeting optimal protein delivery in parenteral and enteral nutrition for preterm infants: a review of randomized, controlled trials.

Close attention to nutritional management is essential for optimizing growth and neurodevelopment of the preterm infant. Protein intake and the protein to energy ratio are the main determinants of growth and body composition. Yet large, multi-center, randomized controlled trials are lacking to guide protein delivery for the preterm infant. Until these studies are pursued, smaller trials must be used to inform clinical practice. This review summarizes the randomized controlled trials that have been performed to test the impact of higher vs. lower protein delivery to the preterm infant. We consider the trials that varied protein delivery rates during parenteral and enteral phases of nutrition. Considerable heterogeneity exists across study designs. Still, cumulative evidence from these trials provides a framework for current recommendations for protein intake in the preterm infant.

Docosahexaenoic and arachidonic acid levels in extremely low birth weight infants with prolonged exposure to intravenous lipids.

OBJECTIVE: To report changes in red blood cell long-chain polyunsaturated fatty acids levels in extremely low birth weight (ELBW) infants relative to duration of intravenous lipid emulsion. STUDY DESIGN: Serial blood samples were collected from 26 ELBW infants during the first 2 months of life in the neonatal intensive care unit using a prospective cohort study design. The primary outcome was the change in long-chain polyunsaturated fatty acids levels over the study period relative to a duration of intravenous lipid emulsion of either ≤ 28 days or >28 days. Secondary outcomes included parenteral and enteral nutritional exposures as well as prematurity-associated morbidities. Longitudinal regression estimated changes in fatty acid levels between the 2 exposure groups. RESULTS: Infants with >28 days intravenous lipid emulsion had 36 more days of intravenous lipid emulsion than did those with ≤ 28 days (P < .001). Docosahexaenoic acid significantly decreased over time in all infants and decreased significantly more in infants exposed to intravenous lipid emulsion for >28 days (P = .03). Arachidonic acid significantly decreased over the study period but the decrease was not related to intravenous lipid emulsion duration. Linoleic and α-linolenic acids had significantly larger increases over time in those with longer exposure to intravenous lipid emulsion (P < .01). CONCLUSION: Docosahexaenoic acid status of ELBW infants declined significantly in the first 2 months of life and the decline was significantly greater in those exposed to intravenous lipid emulsion >28 days compared with those exposed ≤ 28 days.

Preterm infant nutrition: considerations for infants at risk of refeeding syndrome.

Refeeding syndrome (RS) in preterm infants is a scenario of fetal malnutrition, primarily resulting from placental insufficiency, followed by a postnatal physiologic adaptation and response to an imbalance of nutrients provided parenterally. Growth restriction and small gestational age status are common findings in infants at risk of developing RS. Adverse clinical outcomes associated with RS may be severe and life-threatening. The biochemical abnormalities that occur in RS may be mitigated through careful monitoring and adaptation of the clinical management of parenteral and enteral nutrition. This perspective reviews the physiology and metabolism in infants with RS and provides suggested approaches to their clinical monitoring and nutritional management.

Administering Parenteral Nutrition in the Neonatal Intensive Care Unit: Logistics, Existing Challenges, and a Few Conundrums.

Use of parenteral nutrition (PN) in the neonatal intensive care unit (NICU) requires evaluating the need for central venous catheters, potential drug incompatibilities, unintentional exposures, and suboptimal energy and nutrient intake during the transition to full enteral nutrition. Risks of photooxidation reactions in PN components, refeeding syndrome, and excess early amino acid intake should prompt the reevaluation of routine practices. The goal of this paper is to review the practicalities, challenges, and conundrums of administering PN in the NICU.

Guidelines for parenteral nutrition in preterm infants: The American Society for Parenteral and Enteral Nutrition.

BACKGROUND: Parenteral nutrition (PN) is prescribed for preterm infants until nutrition needs are met via the enteral route, but unanswered questions remain regarding PN best practices in this population. METHODS: An interdisciplinary committee was assembled to answer 12 questions concerning the provision of PN to preterm infants. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used. Questions addressed parenteral macronutrient doses, lipid injectable emulsion (ILE) composition, and clinically relevant outcomes, including PNALD, early childhood growth, and neurodevelopment. Preterm infants with congenital gastrointestinal disorders or infants already diagnosed with necrotizing enterocolitis or PN-associated liver disease (PNALD) at study entry were excluded. RESULTS: The committee reviewed 2460 citations published between 2001 and 2023 and evaluated 57 clinical trials. For most questions, quality of evidence was very low. Most analyses yielded no significant differences between comparison groups. A multicomponent oil ILE was associated with a reduction in stage 3 or higher retinopathy of prematurity (ROP) compared to an ILE containing 100% soybean oil. For all other questions, expert opinion was provided. CONCLUSION: Most clinical outcomes were not significantly different between comparison groups when evaluating timing of PN initiation, amino acid dose, and ILE composition. Future clinical trials should standardize outcome definitions to permit statistical conflation of data, thereby permitting more evidence based recommendations in future guidelines. This guideline has been approved by the ASPEN 2022-2023 Board of Directors.

The Role of Work as a Social Determinant of Health in Mother's Own Milk Feeding Decisions for Preterm Infants: A State of the Science Review.

In the United States, 10% of infants are born preterm (PT; <37 weeks gestational age) each year and are at higher risk of complications compared to full term infants. The burden of PT birth is borne disproportionately by Black versus non-Black families, with Black mothers significantly more likely to give birth to a PT infant. One proven strategy to improve short- and long-term health outcomes in PT infants is to feed mother's own milk (MOM; breast milk from the mother). However, mothers must make decisions about work and MOM provision following PT birth, and more time spent in paid work may reduce time spent in unpaid activities, including MOM provision. Non-Black PT infants are substantially more likely than Black PT infants to receive MOM during the birth hospitalization, and this disparity is likely to be influenced by the complex decisions mothers of PT infants make about allocating their time between paid and unpaid work. Work is a social determinant of health that provides a source of income and health insurance coverage, and at the same time, has been shown to create disparities through poorer job quality, lower earnings, and more precarious employment in racial and ethnic minority populations. However, little is known about the relationship between work and disparities in MOM provision by mothers of PT infants. This State of the Science review synthesizes the literature on paid and unpaid work and MOM provision, including: (1) the complex decisions that mothers of PT infants make about returning to work, (2) racial and ethnic disparities in paid and unpaid workloads of mothers, and (3) the relationship between components of job quality and duration of MOM provision. Important gaps in the literature and opportunities for future research are summarized, including the generalizability of findings to other countries.

Hypertriglyceridemia in Preterm Infants.

Preterm and critically ill infants are at risk for hypertriglyceridemia (HTG). Common risk factors for HTG include prematurity, intravenous lipid emulsion dose and oil composition, reduced lipoprotein lipase activity, fetal growth restriction, sepsis, and renal failure. Despite these risk factors, clinicians lack a universally agreed upon definition for HTG and evidence-based approach to HTG management. This review provides a detailed overview of triglyceride and intravenous lipid emulsion metabolism and how this relates to specific HTG risk factors, along with some practical considerations for managing HTG in the neonatal population.

Providing Breastfeeding Support During COVID-19: A Survey of Staff Experiences.

BACKGROUND: The COVID-19 pandemic presents unique challenges to maternity settings. Its influence on providing in-hospital lactation support has not been well described. RESEARCH AIM: To describe the experiences of healthcare workers as they provided in-hospital lactation support during the pandemic. METHODS: A prospective, cross-sectional, online survey evaluated healthcare providers working with postpartum women and newborns affected by COVID-19 at an academic center during March-June 2020. Providers were queried regarding the influence of COVID-19 and COVID-19-specific policies on providing lactation support. Questions assessed guidance received, perceived stress, difficulty providing care, and solicited qualitative responses. The constant comparative method was used to analyze qualitative data. RESULTS: Of 108 providers, 70 (65%) completed the survey. Of 57 providing direct lactation support to women affected by COVID-19, most (n = 39, 67%) reported increased stress. Participants reported lower stress scores when receiving guidance through shift meetings or email compared to those not receiving this guidance [stress score with shift meeting guidance (M [SD]): 3.10 (0.88); score without guidance: 3.83 (0.66); n = 39, p = .009; score with email guidance: 3.79 (0.58); score without guidance: 4.50 (0.58); n = 18, p = .045). Qualitative responses (n = 67; 96%) identified three themes: visitor restrictions allowed less distraction during lactation support; physical separation disrupted maternal/infant bonding; workflow challenges resulted from policy changes and supply access. CONCLUSIONS: Most participating staff providing lactation support to participants affected by COVID-19 reported increased stress. Ensuring written or verbal guidance may reduce staff's experiences of stress. Efforts to optimize lactation support during COVID-19 should consider reducing distractions, physical separation, and logistic challenges.

Body composition measurement for the preterm neonate: using a clinical utility framework to translate research tools into clinical care.

Body composition analysis to distinguish between fat mass and fat-free mass is an established research approach to assess nutritional status. Within neonatal medicine, preterm infant body composition is linked with later health outcomes including neurodevelopment and cardiometabolic health. Mounting evidence establishing fat-free mass as an indicator of nutritional status, coupled with the availability of testing approaches that are feasible to use in preterm infants, have enhanced interest in measuring body composition in the neonatal intensive care unit (NICU) setting. In this paper, we use the concept of clinical utility-the added value of a new methodology over current standard care-as a framework for assessing several existing body composition methodologies with potential for clinical application to preterm neonates. We also use this framework to identify remaining knowledge gaps and prioritize efforts to advance our understanding of clinically-oriented body composition testing in the NICU.

Human Milk Growth Factors and Their Role in NEC Prevention: A Narrative Review.

Growing evidence demonstrates human milk's protective effect against necrotizing enterocolitis (NEC). Human milk derives these properties from biologically active compounds that influence intestinal growth, barrier function, microvascular development, and immunological maturation. Among these protective compounds are growth factors that are secreted into milk with relatively high concentrations during the early postnatal period, when newborns are most susceptible to NEC. This paper reviews the current knowledge on human milk growth factors and their mechanisms of action relevant to NEC prevention. It will also discuss the stability of these growth factors with human milk pasteurization and their potential for use as supplements to infant formulas with the goal of preventing NEC.

Dietary Fat and Fatty Acid Intake in Nulliparous Women: Associations with Preterm Birth and Distinctions by Maternal BMI.

BACKGROUND: Evidence documenting whether diet quality, particularly dietary fatty acids, is associated with preterm birth (PTB) is limited. OBJECTIVE: The aim was to measure associations between dietary fatty acid intake prior to pregnancy, specifically n-3 (É·-3) PUFAs and odds of PTB in US women and determine if associations differed by prepregnancy BMI. METHODS: We designed a secondary analysis of dietary intake in nulliparous women enrolled in a longitudinal cohort (NCT01322529). Participants completed an FFQ, modified to assess detailed PUFA intake, during the 3 mo preceding pregnancy. Inclusion in this analytic cohort required total energy intake within 2 SDs of the group mean. Prepregnancy BMI was categorized as underweight, normal, overweight, or obese. The primary exposure was estimated intake of EPA and DHA (combined EPA+DHA), in the context of a recommended intake of 250 mg. The primary outcome was PTB (<37 wk). Adjusted regression models controlled for maternal factors relevant to PTB and evaluated associations with PUFAs. Interaction terms estimated effect modification of BMI. A false discovery rate (FDR) correction accounted for multiple comparisons. RESULTS: Median daily intake of combined EPA+DHA in 7365 women was 70 mg (IQR: 32, 145 mg). A significant interaction term indicated the effects of EPA+DHA on odds of PTB were different for different BMI categories (P < 0.01). Specifically, higher intake of combined EPA+DHA was nominally associated with reduced odds of PTB in women with underweight (OR: 0.67; 95% CI: 0.46-0.98) and normal BMI (OR: 0.87; 95% CI: 0.78-0.96), yet was associated with increased odds of overweight BMI (OR: 1.21; 95% CI: 1.02-1.44). Associations remained significant after FDR correction. CONCLUSIONS: Based on a cohort of US women designed to identify predictors of adverse pregnancy outcomes, dietary intake of combined EPA+DHA was considerably lower than recommended. Associations between intake of these recommended n-3 fatty acids and risk of PTB differ by maternal BMI.