Weight and gestational age at birth are the most critical determinants of infant morbidity and mortality. Preterm deliveries resulting in low or very low birth weight (LBW and VLBW)—less than 2500 g or 1500 g, respectively—remain a serious problem in perinatal health care worldwide. In industrial countries, such as the United States, 6–10% of infants, approximately 300,00 annually, are LBW (1). Preterm is the most common cause of infant morbidity and mortality (1). The immediate consequences of immaturity at birth include respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis; long-term morbidity includes cerebral palsy, impaired vision and hearing, cognitive impairment, and possible cardiovascular disease in adulthood (2–4). Costs associated with preterm birth are estimated at several billion dollars per year (4). Reducing the incidence of preterm birth and prolonging gestation for those at risk of delivering preterm depend on the identification and remediation of factors causing preterm birth and premature rupture of membranes. Evidence suggests that aspects of essential fatty acids (EFA) and their metabolites of both the linoleic acid (n-6) and the linolenic acid series (n-3) play important and perhaps modifiable roles in prolonging gestation in both laboratory animal and human studies. Essential Fatty Acid Metabolism Synthesis of linoleic acid (18:2n-6, LA) and α-linolenic acid (18:3n-3, LnA) does not occur in higher animals; these EFA are required in the diet. Dietary LA serves as the precursor for the n-6 series of polyunsaturated fatty acids (PUFA), and dietary LnA is the precursor for the n-3 PUFA series. It has been suggested that man evolved on a diet with a n-6:n-3 ratio of approximately 1:1, whereas the current diet ranges from 10:1 to 25:1 (5). This leads to concerns that today’s diet may be insufficient to meet n-3 EFA requirements. Particular concern regarding docosahexaenoic acid (DHA, an elongation and desaturation metabolite of LnA) has been voiced, since evidence suggests that it has an essential function in neural and other tissues (6,7). Arachidonic acid (AA) and other long-chain n-6 and n-3 PUFA are not essential per se since they can be synthesized from dietary LA and LnA. Long-chain PUFA derivatives of LnA and LA, however, are not functionally interchangeable, and biosynthetic problems could arise given the present dietary n-6:n-3 ratio. The same series of microsomal desaturase and elongation enzymes metabolize both the n-6 and n-3 families of PUFA. Kinetic studies in liver microsomes (8) and isolated hepatocytes (9,10) report that ∆6-desaturase is the rate-limiting enzyme in this process. The two parent EFA (LA and LnA) and oleic acid (18:1n-9) compete for the microsomal enzyme systems that allow further desaturation and elongation. Binding affinity for ∆6-desaturase is highest for LnA, high for LA, and lowest for oleic acid (11). For this reason, desaturation and elongation of 49 PUFA generally is observed only under conditions of n3 and n-6 EFA deficiency (EFAD). A common metabolic response seen in n-3 EFAD is a compensatory increase in n-6 FA, particularly docosapentaenoic acid (22:5n-6, DPA) and to a lesser extent, 22:4n-6. Neural tissue of n-3 FA deficient animals showed a 45-fold increase in DPA compared to controls (12–15). Faced with both n-3 and n6 EFA deficiencies, n-9 long-chain (LC) PUFA derivatives, especially eicosatrienoic acid (20:3n-9), are elevated. Humans convert dietary LnA to both eicosapentaenoic acid (20:5n-3, EPA) and DHA, but the capacity for this conversion is limited. If dietary LnA is sufficient and the diet does not provide excessive LA, humans can synthesize sufficient EPA and DHA for tissue needs. However, the amount of dietary LnA and the n-6:n-3 ratio of the diet, due to excessive LA consumption (estimated to provide 7% of caloric intake), is of concern because conversion to n-3 long-chain polyunsaturated fatty acids (LCPUFA) may be limited. Dietary sources of preformed n-3 long-chain fatty acids (LCFA) can provide large amounts of these fatty acids and are primarily derived from certain species of fish in human diets (also fish oils or marine lipids). Thus, commonly consumed human diets in the United States may provide small amounts of LnA, and large amounts of LA that decrease LnA conversion to its desaturation and elongation products, EPA and DHA; this combined with infrequent fish consumption could lead to low n-3 LCPUFA status.