March 1978 The Journal o f P E D I A T R I C S

461

Cord blood fatty acid composition in infants and in their mothers during the third trimester since essential fatty acids are required for normal brain development, we studied plasma lipids and EFA levels in 16"postpartum mothers (28 to 44 weeks) and in the umbilical vein and artery of 32 newborn infants. Groups of eight 24 to 33-, 34 to 37-, 38 to 42-, and 43 to 44-week-old infants were studied. Plasma fatty acid composition was studied in PL, CE, TG, and FFA by thin-layer and gas-liquid chromatography. Increased values for PL, CE, and TG (P < 0.001) were noted in maternal plasma compared to cord plasma; linoleic acid was lower (P < 0.001) in cord plasma PL, CE, and FFA. EFA derivatives dihomo-y-linolenic, arachidonic, and docosahexaenoic acids' were higher in cord plasma (P < 0.001). Total polyenoic EFA increased with advanced gestation, and at term, was close to maternal levels. A-5,8,11-eicosatrienoic acid (elevated in EFA deficiency) was elevated in cord plasma as compared with maternal values (P < 0.001)," other criteria of EFA deficiency were absent. These data indicate that fetal EFAs are elongated and desaturated during the third trimester. These higher polyenoic acids may incorporate into lipids in the developing CNS. The lower linoleie acid levels in the fetus may be important to the transplacental transport of EFA.

Zvi Friedman, M.D., F.R.C.P.(C),* A b r a h a m D a n o n , M.D., Ph.D., Edwin L. Lamberth, Jr., M.D., and W i l l i a m J. M a n n , M . D . ,

Hershey,

Pa.,

N e g e v , Israel, a n d N a s h v i l l e , T e n n .

NORMAL GROWTH of infants is dependent upon an adequate supply of essential fatty acids.' The human fetus, like the adult, is unable to synthesize the essential fatty acids, which must be derived from the maternal circulation and pass through the placenta. Polyunsaturated fatty acids derived from the dietary essential fatty acids, linoleic and linolenic, occur in high concentration in the central nervous System,-' and the brain content of longchain polyunsaturated fatty acids--arachid0nic and docosahexaenoic-increases rapidly during brain organogenesis.:~ Prolonged limited periods of essential fatty acid

deficiency during pregnancy in mice produced irreversible impairment of the offspring's behavior. ~ Although human brain contains a considerable amount of polyunsaturated fatty acids, very little is known of the requirements for fatty acids essential to support normal development of the human fetus. The incidence of neurologic and psychological handicaps is higher in low-birthAbbreviations used CNS: central nervous system EFA: essential fatty acid PL: phospholipid CE: cholesterol ester TG: triglyceride FFA: free fatty acid

From the Departments of Pediatrics and Obstetrics and Gynecology, The Milton S. Hershey Medical Center, The Pennsylvania State University, the Department of Pharmacology, The Ben Gurion University of the Negev Israel, and the Department of Medicine, Vanderbilt University Hospital *Reprint address: Department of Pediatrics, Division of Newborn Medicine, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033.

weight infants than in appropriately grown term infants, ~-7 and the level of linoleic acid in early fetal tissues is less than that seen in adults? but the level is known to increase with advancing gestational age? Low-birth-weight infants sustained on fat-free paren-

0022-3476/78/0392-0461500.60/0 9 1978 The C. V. Mosby Co.

VoL 92, No. 3, pp. 461-466

4 62

Friedman et aL

The Journal of Pediatrics March 1978

Table I. Clinical data for study groups

Data

[

Time of study (gestational wk) Range Mean • SD Birth weight (gm) Range Mean • SD Sex Male Female Number of subjects

Mothers

28-36 32.4 ___2.5

Infants

37-44 39.5 • 2.5

8

24-33 28 • 3.5

34-37 35.3 • 1.2

38-42 39.8 _+ 1.5

43-44 43.3 _+ 0.5

490-1,720 955 _+ 394

1,750-2,636 2,269 ___506

3,120-4,125 3,541 • 329

3,231-4,564 3,853 • 347

4 4 8

5 3 8

4 4 8

6 2 8

8

Table II. Concentration of plasma lipids at birth* (mg/dl)

Mother (wk of pregnancy) Constituent Phospholipids Cholesterol esters Triglycerides Free fatty acids

Infant? (gestationalage in wk)

37-44

24-33

314.0 • 24.7

313.3 _+ 17.7

95.9 • 15.2

98.1 _+ 20.2

102.3 • 13.3

106.9 • 14.3

1995 _+ 24.3 185.0 • 42.2

193.0 _+ 37.0 193.6 • 56.0

50.0 • 22.5 28.1 _+ 11.7

51.5 _+ 12.8 27.6 • 12.5

54.0 • 17.6 25.3 _+ 10.6

55.7 • 20.1 30.0 • 9.1

16.0 _+ 9.5

18.0 _+ 8.9

7.6 • 4.1

8.4 • 5.2

6.8 • 4.3

8.7 • 3.9

28-36

I

[34-37138-42{43-44

*Mean _+ SD. tConcentration of lipids in cord blood is presented as the mean concentration of lipids in umbilical vein and artery. teral alimentation rapidly develop essential fatty acid deficiency during the first few days of life. 1~ Since lipids, and in particular those containing the essential fatty acids, are important constituents of biological m e m b r a n e s and also serve as prostaglandin precursors, we have measured their levels in cord venous and arterial blood of infants and compared them to maternal plasma levels during the second half of pregnancy, in order to gain further understanding of the role of essential fatty acids in the nutrition of the developing h u m a n being. MATERIALS

AND METHODS

Patients. The series comprised 16 healthy postpartum women and 32 Caucasian infants. All were selected at random from the obstetric and nursery services at Vanderbilt University Medical Center and the Milton S. Hershey Medical Center. Consent was obtained from each mother. Gestational age was estimated according to the last menstrual period and examination o f the infant, tl The clinical data of the study group are shown in Table I. All the mothers consumed a diet that did not differ significantly from that of an average American middleclass population. All had supervised, uncomplicated pregnancies and deliveries, and the infants were all born after

vaginal delivery. Only normally grown (tenth to ninetieth percentile) infants were studied. 1~ The infants and mothers were divided randomly into study groups according to gestational age. Each group contained eight subjects (Table I). Methods. Whole blood with E D T A added was obtained via peripheral venipuncture from mothers within 15 minutes after delivery. At the time of delivery the umbilical cord was doubly clamped (first distally), and 1.0 ml of blood was obtained by puncture of the umbilical vein and artery. The blood was centrifuged at 4~ and the plasma was removed and stored at - 2 0 ~ in 100% nitrogen until lipid-extraction was begun. The various lipid fractions, i.e., PL, CE, TG, and FFA, were separated by thin-layer chromatography. The fatty acid composition of each lipid fraction was then determined by gas-liquid chromatography. These methods have been described previously. 1~ Student's t test for paired and unpaired data was used for statistical analysis. RESULTS

Concentrations of main lipid classes in plasma (Table lI). Maternal and cord plasma concentrations of PL, CE, TG, and F F A were found to be similar for different

Volume 92 Number 3

Cord blood fatty acid

463

Table llI. Fatty acid composition of plasma phospholipids in mothers and their infants*

Gestational age (wk)

Difference mother-infant (UV)

Mothers

24-33 UV

34-37 UV

c 16:0 c 16:1

30.0 4- 3.1 0.8 • 0.3

32.1 • 4.0 2.0 • 0.4

31.9 • 2.8 1.2 ___ 0.2

29.8 • 2.1 29.4 4- 0.6 1.1 4- 0.4 1.5 • 0.2

--2.1 -1211

--1.9 -0.4ll

+0.2 -0.3~

+0.6 -0.711

c 18:0

10.4 • 0.9

14.1 • 1.0

15.4 •

1.5

14.5 _+ 0.5

-1.6

-3.711

-5.011

4.111

c 18:1 099

15.6 •

12.2 •

1.3

10.7 ___ 1.6

11.2 • 2.0

+0.5

+3.411

+4.411

+3.911

c 18:2 096 c 20:3 099

21.2• N

12.0 • 3.0 aw bll 15.1 _+ 3.0 a,b,dw 5.44-2.7 1.5 4- 0.1

7.9• 1.6 _+ 0.7

7.1 • 0.9 1.8 • 0.6

7.3 ___ 0.8 2.5 + 0.5

-1.511

+ 13.311 -1.611

+ 14.111 -1.811

+ 13.911 2.511

4.3 4- 0.7

4.5 _+ 1.0

5.0 4- 0.3

+1.1:~

-0.7

0.9w

-1.411

1.9

17.2 + 0.7

--2.811

-2.011

-6.511

-6.0[[

6.6 4- 1.9

6.5 _+ 2.4

+0.3

--0.2

-2.75

-2.6~

Fatty acid~ methyl esters

I 38-42 UV

43-44 UV

I

24-33

34-37

38-42

I

43-44

b~ 1.4

+

15.811

b, dll c 20:3 09 6

3.6 4- 0.7

c 20:4 096

11.2_+2.4

c22:6093

3.9+2.1

2.5 • 0.6 a, b, d~ 14.04-3.9 b, dw 3 . 6 + 1.0

17.4• 4.1 4-2.5

17.7 •

N = Data omitted less than 0.5% of total. a = Comparison of values between 24-33 to 34-37 weeks. b = Comparison of values between 24-33 to 38-42 weeks. d = Comparison of values between 24-33 to 43-44 weeks. *Data reported as mean percentage _+ SD of total fatty acid methyl esters. tc 16:0 (palmitic), c 16:1 (palmitoleic), c 18:0 (stearic), c 18il 09 9 (oleic), c 18:2 09 6 (linoleic), c 20:3 099 (5, 8, 11 eicosatrienoic), c 20:3 09 6 (dihomo-'~-linolenic acid), c 20:4 09 6 (arachidonic), c 22:6 09 3 (docosahexaenoic). :~Significant level < 0.05. w level < 0.01. [[Significant level < 0.001.

Table IV. Fatty acid composition of plasma cholesterol esters in mothers and their infants*

Gestational age (wk) Mothers

24-33 UV

34-37 UV

c 16:0 c 16:1

11.9 • 1.0 4.0 + 0.9

17.3 4- 4.0 8.6 + 1.8

20.0 + 1.6 10.3 + 1.1

c 18:0

0.9 4- 0.5

Fatty acid'~ methyl esters

Difference mother-infant (UV) I

38-42 I UV I

43-44 UV

19.8 + 1.7 20.2 4- 0.6 8.1 • 1.9 10.1 + 1.7

24-33

34-37

38-42

43-44

--5.4w --4.611

--8.111 --6.311

--7.9[[ --4.111

--8.311 --6.111

a~ c 18:1o9 9

23.5 4- 1.8

c 18:2 096

48.1 +_ 4.7

4.3 +_ 0.8 aw d II 42.2 4- 1.2 a,b,d]] 8.0 + 3.0

0.5_+0.2

a, b, all 0.4+0.6

c 20:3 096

aw c20:4096

7 . 0 4 - 1.8

b,d,I I

2.9 • 0.8 c~ 36.2 • 3.7

2.6 _+ 0.7

-3.41[

-2.0w

--1.9w

-1.7w

31.1 4- 3.4 33.1 • 6.4

-18.711

-12.711

-7.611

9.611

16.0 _+ 0.8

16.8 +_ 1.9

+40.111

+32.111

+31.311

+32.411

+0.1

-0.3~

-0.611

+0.2

--4.0w

8.611

0.8•

2.8 4- 1.0

1.1_+0.2

15.7 • 5.5 0.7•

-0.2

c,e~ 11.0+3.0

15.6•

15.5+3.9

-8.511

6.8 4- 2.7 a = Comparison of values between 24-33 to 34-37 weeks_ b = Comparison of values between 24-33 to 38-42 weeks. c = Comparison of values between 34-37 to 38-42 weeks. d = Comparison of values between 24-33 to 43-44 weeks. e = Comparison of values between 34-37 to 43-44 weeks. *Data reported as mean percentage _+ SD of total fatty acid methyl esters. tc 16:0 (palmitic), c 16:1 (palmitoleic), c 18:0 (stearic), c 18:1609 (oleic), c 18:2096 (linoleic), c 20:3096 (dihomo-3,-linolenic acid), c 20:4096 (arachidonic). ~Significant level < 0.05. w level < 0.01. IISignificant level < 0.001.

464

Friedman et al.

The Journal of Pediatrics March 1978

T a b l e V. F a t t y a c i d c o m p o s i t i o n o f p l a s m a t r i g l y c e r i d e s in m o t h e r s a n d t h e i r i n f a n t s *

Gestational age (wk) Fatty acidt methyl esters

Mothers

24-33 UV

32.3 _ 2.5

25.6 • 3.2

34-37 UV

38-42 UV

Difference mother-infant (UV) 43-44 UV

] 24-33

I 34-37

38-42

43-44

+6.7w

+3.1

+3.7

+3.2

7.9 • 0.4 6.4 _+ 0.8

3.3 --3.711

4.0~ --3.5il

--4.3w ~2.911

-5.4H -3.611

42.6 • 4.1

37.7 _+ 5.5 38.3 _+ 7.7

-6.4w

+0.2

+5.12

+4.5~

9.3 • 1.8

11.8 _+ 2.1 10.9 • 3.3

+9.611

+8.411

+5.9w

+6.8w

-1.4:[:

-1.6~

-3.7w

--2.9w

a~ 16:0

29.2 _+ 1.5

28.6 • 2.9 29.1 • 2.0

d~ 16:1 18:0

2.5 • 2.0 2.8 • 0.7

18:1 co9

42.8 • 3.2

18:2o96

17.7 • 2.8

20:4oJ6

0.5 • 0.3

5.8 • 1.6 6.5 • 2.3 aw b, dll 49.2 • 0.5 b, d$ 8.1 • 2.0 b2 1.9 • 2.1

6.5 _+ 1.5 6.3 _+ 1.5

2.1 • 1.2

6.8 • 1.6 5.7 • 1.5

4.2 • 1.7

3.4 • 2.0

a = Comparison of values between 24-33 to 34-37 weeks. b = Comparison of values between 24-33 to 38-42 weeks. d = Comparison of values between 24-33 to 43-44 weeks. *Data reported as mean percentage _+ SD of total fatty acid methyl esters. tc 16:0 (palmitie), e 16:1 (palmitoleic), c 18:0 (stearic), c 18:1 r 9 (oleic), e 18:20l 6 (linoleie), c 20:4 co 6 (arachidonic). :~Significant level < 0.05. w level < 0.01. I/Significant level < 0:001.

T a b l e VI. C o m p o s i t i o n o f p l a s m a free f a t t y a c i d s i n m o t h e r s a n d t h e i r i n f a n t s *

Gestational age (wk) Fatty acids~ methyl esters

Mothers

16:0 16:1 18:0 18:1 o)9

27.6 3.5 14.8 42.0

-+ 2.3 -+ 2.0 -+ 3.5 • 3.2

18:2 r 6

12.0 _ 1.9

24-33 UV 36.7 4.3 19.6 21.6 b, 3.2

• 3.6 • 0.6 • 3.2 • 5.8 d~ + 1.9

34-37 UV

38-42 UV

38.7 • 1.0 5.2 _+ 0.5 19.6 • 2.7 21.3 _+ 3.0 c, e2 3.2 • 2.8

34.2 4.2 18.2 24.2

Difference mother-infant (UV) i I 43-44 I UV

__+ 5.7 40.9 • 5.1 + 0.9 5.5 • 0.5 • 3.0 20.1 _+ 2.9 • 5.9 17.3 _+ 0.6

10.1 +_4.0

9.4_+ 1.6

24-33

34-37

38-42

43-44

--9.1w --0.8 --4.82 +20.411

-11.ill --1.73~ --4:8:~ --20.7Jl

-6.6 --0.7 --3.42 + 17.811

-13.311 --2.0 --5.3:~ +24.7dl

+8.811

+8.811

+1.9

+2.6

b = Comparison of values between 24-33 to 38-42 weeks. c = Comparison of values between 34-37 to 38-42 weeks. d = Comparison of values between 24-33 to 43-44 weeks. e = Comparison of values between 34-37 to 43-44 weeks. *Data reported as mean percentage _+ SD of total fatty acid methyl esters. % 16:0 (palmitic), c 16:1 (palmitoleic), c 18:0 (stearic), c 18:1609 (oleic), c 18:2~06 0inoleic). :~Significant level < 0.05. w level < 0.01. IlSignificant level < 0.001.

g e s t a t i o n a l ages, N o d i f f e r e n c e s in t h e c o n c e n t r a t i o n s o f

( P < 0.001). T h e l o w e s t levels o f this f a t t y acid w e r e

the m a i n lipid c l a s s e s w e r e f o u n d in c o r d v e n o u s a n d

n o t e d b e f o r e 34 w e e k s g e s t a t i o n . H o w e v e r , v e n o u s a n d

arterial p l a s m a . T h e c o n c e n t r a t i o n s o f P L , CE, a n d T G

arterial

were

in

( P < 0.001) o f t h e m o r e u n s a t u r a t e d e s s e n t i a l f a t t y a c i d -

Fatty acid composition of plasma phospholipifls (Table

c o n c e n t r a t i o r r o d d o c o s a h e x a e n o i c acid, w h i c h is a h o m o -

III). N o d i f f e r e n c e s in t h e f a t t y acid c o m p o s i t i o n o f t h e

l o g u e o f t h e " l i n o l e n i c a c i d " series, w a s n o t e d to b e h i g h e r

phospholipids were found in cord venous and arterial

in c o r d b l o o d p l a s m a at t e r m as c o m p a r e d w i t h m a t e r n a l

p l a s m a . T h e c o n c e n t r a t i o n o f linoleic acid in c o r d p l a s m a

levels23 T h e c o n c e n t r a t i o n o f t h e f a t t y acid 5 , 8 , 1 1 - e i c o s a -

p h o s p h o l i p i d w a s less t h a n 40% t h a t o f t h e m a t e r n a l v a l u e

trienoic acid w a s f o u n d to b e h i g h e r ( P < 0.001) in c o r d

significantly

higher

(P

Cord blood fatty acid composition in infants and in their mothers during the third trimester.

March 1978 The Journal o f P E D I A T R I C S 461 Cord blood fatty acid composition in infants and in their mothers during the third trimester sinc...
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