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Lipids do not seem to be transported across the placenta and are not found in AF after maternal injection. Biezenski⁸⁷ described the lipid content of AF from the 26th week of gestation. The phospholipids measured included lysophosphatidylcholine, sphingomyelin, phosphatidylcholine, inositol, serine, ethanolamine, phosphatidic acid, and cardiolipin. Biezenski also established values for total fatty acids, including palmitic acid, palmitoleic acid, stearic acid, oleic acid, and linoleic acid. This author concluded that total lipid was about 1–2 percent of that found in maternal plasma during pregnancy and about 5 percent of that found in fetal plasma.

Phosphatidylserine normally found in AF and in the placenta is not present in maternal plasma, whereas the sphingomyelin content of AF is much lower than in plasma.⁸⁷ Total cholesterol represents roughly one‐third of the total lipids in AF. Biezenski⁸⁷ observed that the lipid profile remained essentially unchanged in the third trimester, despite the striking increase in AFV during this period. Near term, the placenta prevents the transfer of maternal esterified fatty acids in the form of phospholipids, triglycerides, or cholesteryl esters, although appreciable amounts of unesterified fatty acids and free cholesterol are transferred.⁸⁸ AF collected more than 2 weeks after fetal death shows increased total lipid concentrations due mainly to increased free cholesterol, unesterified fatty acids, and hydrocarbons.

Pomerance et al.⁸⁹ observed no specific diagnostic lipid pattern in their detailed lipid analyses of various complicated pregnancies, including hemolytic disease of the newborn, toxemia of pregnancy, diabetes, anencephaly, and hydramnios. Gardella et al.⁹⁰ found an association between lipopolysaccharide‐binding protein and soluble CD14 and preterm labor.

In pregnancies affected by autosomal recessive Smith–Lemli–Opitz syndrome (SLOS), Dallaire et al.⁹¹ and Tint et al.⁹² found that low cholesterol and elevated 7‐dehydrocholesterol (7‐DHC) values were pathognomonic of the disorder. Mutation analysis of the 7‐dehydrocholesterol reductase gene⁹³ on DNA derived from chorion villus samples or AF cells^{94, 95} has brought precision to this prenatal diagnosis. Observation of low maternal serum unconjugated estriol,⁹⁶ or accumulation of 7‐ and 8‐DHC in AF,⁹⁷ would prompt mutation analysis.^98–100 Prenatal diagnosis can be made on the basis of malformations consistent with the syndrome, intrauterine growth restriction, and sterol analysis in AF or chorionic villi.^{101, 102}

Other sterols in AF including lathosterol, desmosterol, lanosterol, and dimethylsterol, when deficient, may signal a prenatal diagnosis of lathosterolosis, desmosterolosis, X‐linked chondrodysplasia, and the Antley–Bixler syndrome.⁹⁷

The fatty acid composition of AF¹⁰³ differs considerably from that found in maternal plasma. Fetal renal excretion seems to be the origin of part of the free fatty acids in AF, at least during the third trimester. The immunosuppressive activity of AF may be due to lipid‐like factors providing a nonspecific immunoregulatory mechanism that prevents the immune rejection of the conceptus by the mother.¹⁰⁴

Studies of bile acid concentrations in normal and pathologic pregnancy revealed elevated bile acid concentrations in the AF of fetuses with intestinal obstructions.^{105, 106} Such results are expected for all intestinal obstructions distal to the ampulla of Vater, where the fetal stomach content will be regurgitated into AF.¹⁰⁷ In general, the mean bile acid concentrations in the AF were similar to those in the serum. However, in paired samples from individual patients, these two values did not correlate well.¹⁰⁵

Gluck and Kulovich pioneered the analysis of AF phospholipids for the assessment of fetal pulmonary maturity.¹⁰⁸ The surface‐active phospholipids lecithin (L) and sphingomyelin (S) originate from the fetal lungs. A marked increase in the production of lecithin occurs at about 35 weeks of gestation.¹⁰⁹ As lecithin passes from the lung into the AF, an increase in the L/S ratio in AF occurs. The correlation of L/S ratio with gestational age is well established.¹¹⁰ Various pregnancy complications have a marked effect on the maturation of the fetal lung and hence the L/S ratio. Conditions that affect fetal lung maturation, including maternal hypertension, placental insufficiency, and diabetes mellitus, render the L/S ratio less valuable.¹⁰⁸

Lamellar bodies store phospholipids that serve as pulmonary surfactant to reduce surface tension, which is essential for lung maturity. Lamellar body count¹¹¹ and surfactant‐to‐albumin ratio in AF for predicting the risk of respiratory distress syndrome are equally accurate and to an important extent eliminate L/S ratio‐identified false‐positive cases of fetal lung maturity.¹¹² Whereas the general consensus is that amniocentesis to determine fetal lung maturity should not guide timing of delivery,¹¹³ this remains controversial especially for rural obstetrics practices.¹¹⁴ At Mayo Clinic, lamellar body count (LBC) is the test of choice for fetal lung maturity, with reflex to L/S ratio when LBC is indeterminate (MJ Wick, personal communication).