Thoughts on fetal growth: tissues and nutrition

Professor Oreste Battisti,

Professor Oreste Battisti,

ULg Faculty of Medicine

ULg Faculty of Medicine

Pediatrics and neonatology

The Fetal and postnatal growth :

the analysis of commonly used anthropometric charts

CM Drillien and F Cockburn: « Neonatal medicine »

 Growth contains different dimensions or vectors

It can be assessed by

- absolute indices: Weight, length, HC, skinfolds, circumferences,… - relative indices (ratios between indices):

-The velocity of indices

 Difficulties of growth in utero and afterwards changes

the relative importance of vectors



The charts

Périods in weeks d BW g d BL cm d HC cm dBWg/dBLcm dBWg/dHCcm dBLcm/dHCcm 26-28 115 ( 70- 160 ) 1 (.85-1.15) 1.1( 0.9 -1 .2 ) 115( 35-115 ) 110( 100-133) 0.9( 0.95-1 ) 28-30 145 ( 100- 190 ) 1.13( 0.63-1.63) 0.9( 0.7 – 1.3 ) 125( 90-160 ) 164( 115-213 ) 1.34( 0.44-2.24 ) 30-32 170 ( 108-232 ) 1.2(.94– 1.54) 0.7( 0.7-1.3 ) 182( 86-288 ) 242( 117-376 ) 1.35( 0.9-1.79 ) 32-34 208 ( 148-268 ) 1.23(.94- 1.54 ) 0.8( 0.65-0.95 ) 178( 70-286 ) 253( 153-353 ) 1.56( 0.97-2.15 ) 34-36 242 ( 167-317 ) 1( 0.6 – 1.4 ) 0.7( 0.15-0.9 ) 272( 174-370 ) 392( 184-600 ) 1.5( 1.1-2.5 ) 36-38 213 ( 129 – 297 ) 0.8( 0.3 – 1.3 ) 0.5( 0.2-0.8 ) 273( 166-380 ) 459( 87-731 ) 1.8( 1.1-2.5 ) 38-40 143 ( 43-243 ) 0.7( 0.1 – 1.3 ) 0.33( 0.13-0.53 ) 310( 0- 645 ) 621( 0-1321 ) 2.4( 0.5-0.34 ) 40-42 70 ( 0 – 168 ) 0.25( 0 – 0.6 ) 0.17( 0 – 0.48 ) 280( 0 – 583 ) 420( 0 – 400 ) 1.47( 0- 1.25 ) Mean 170 ( 57 – 283 ) 0.9(.15 – 1.65 ) 0.6( 0.04-1.1 ) 223( 82-366 ) 355( 14-686 ) 1.66( 0.88 – 2.44 )



Stage I (Hyperplasia)

- 4 to 20 weeks

- Rapid mitosis

- Increase of DNA content



Stage II (Hyperplasia &

Hypertrophy)

- 20 to 28 weeks

- Declining mitosis.

- Increase in cell size.



Stage III ( Hypertrophy)

- 28 to 40 weeks

- Rapid increase in cell size.

- Rapid accumulation of fat, muscle and

connective tissue.



95% of fetal weight gain occurs during



MRO2: 6 – 8 ml/kg/m



BMR and MRO2

increase with GA



CH:

glucose ( proportional to

mother ) and lactate

( from the placenta )



High de novo

lipids

_glycogen

proteins

NEFA,glycerol

_glucose

Am acids

CO2 + ATP

hGH, E, NE

Glucagon, ACTH,

T4

I

cortisol

Glucagon,

E, NE,T4

I, hGH

_Cortisol

Insulin

Insulin

Cortisol,

glucagon

cortisol

I

hGH,

Gucagon,

E, NE, ACTH

T4



ATP and 5-Pentose;



In- and out-cells

composition



Defenses against FR and

EAA



BMR



Muscles ( FFA ) and

intestines ( glutamine

and KB ) have

- secretion +

secretion

+

resistance

fructose hGH, ACTH, cortisol, T4, HPL,

glucagon, endorphins

Hypo-K+

AA,

ILeu

KB,



The secretion of insulin in utero

The role of insulin in utero



The receptors to insulin in utero

Authors weight length HC « type »: At birth postnatal -> 60 weeks parameters Lubchenco 1966

22 % 11% 10 % Diagnostic Ponderal index

Usher-Mc Lean 1969 26 % 8 % 6 % Diagnostic Babson 1970-1976 14 % 8 % 9 % Diagnostic Gairdiner 1971 17 % 4 % 4 % Diagnostic and postnatal Battisti 1990 13 % 7 % 6 % Diagnostic postnatal Ponderal index, LAC, LAC/HC, tricipital skf, several organs muscles Dombrowski 1996 13 % 5 % 4 % diagnostic

Author(s), year(s) Intervals in weeks , parameters CV : BW CV : BL CV : HC Babson, 1970,1976 26-42 ; 26-92 ; BW,BL,HC 14 8 9 Battisti, 1992 25-60 ; BW,BL,HC,PI 13 7 6 Dombrowski 1992, 26-42 ; BW,BL,HC 13 5.3 4 Gairdner 1971 26-60 ; BW,BL,HC 17 4.4 4 Lubchenco 1966, 1970 26-42 ; BW,BL,HC, PI 22 11 10 Usher-McLean 1969 25-44 ; BW,BL,HC 26 8 6

Author PCA and BW PCA and BL PCA and HC Babson * BW= 176 PCA – 3696, SD = 2401 ; r = . 99 BL = 0.8 PCA + 17.5, SD = 10.8 ; r = . 99 HC= 0.48 PCA + 14, SD = 6.63 ; r =. 98 Battisti * =174 APC – 3665, SD = 434 ; r = .99 = 0.9 APC + 11.5, SD = 4; r= . 99 = 0.6 APC + 9.72,SD = 2.4 ; r= . 98 Dombrowski * = 174 APC – 3732, SD = 1262; r=.99 = 1.06 APC + 6.64, SD = 7.8; r=. 99 = 0.721 APC + 5.3, SD = 5.3; r = . 98 Gairdner * = 206 APC – 5051, SD = 2672; r = . 98 = 0.89 APC +13.6, SD = 13; r =. 99 = 0.5 APC + 13.94, SD = 6.5; r = . 98 Lubchenco * = 163 APC – 3375, SD = 1303; r =. 99 = 1.25 APC + 2.5, SD = 7.1; r =. 99 = 0.58 APC + 10.5, DS = 4.8; r =. 97 Usher-McLean * = 177 APC – 3741, SD = 1350; r =. 99 T= 1.11 APC +7, SD = 8.35; r =. 99 = 0.81 APC + 3.1, SD = 6.2; r=.99



Way of characterizing the relationship of height

to mass for an individual.



PI = 1000 x



Typical values are 20 to 25.



PI is normal in symmetric IUGR.



PI is low in asymmetric IUGR.

Mass (kgs)

Height (cms)

3

PCA weeks BW g BL cm HC cm 25 560 ( 90 ) 31.6 ( 2.5 ) 22 ( 1.5 ) 26 720 ( 115 ) 33.1 ( 2.6 ) 23.1 ( 1.6 ) 28 1040 ( 200 ) 36.1 ( 2.8 ) 25.3 ( 1.8 ) 30 1360 ( 218 ) 39.1 ( 3 ) 27.4 ( 1.9 ) 32 1685 ( 275) 42.1 ( 2.5 ) 29.5 ( 1.8 ) 34 2093 ( 335 ) 44 ( 3.5 ) 30.9 ( (2.2 ) 36 2500 ( 430 ) 45.9 ( 2.4 ) 32.2 ( 2.3 ) 38 2932 ( 469 ) 47.7 ( 3.8 ) 33.2 ( 2.3 ) 40 3365 ( 445 ) 49.5 ( 2.6 ) 34.3 ( 1.6 ) 42 3798 ( 608 ) 51.3 ( 4 ) 35.4 ( 2.5 )

PCA weeks BW g BL cm HC cm 25 800 ( 152 ) 35.6 ( 1.4 ) 26.2 ( 1 ) 26 900 ( 175 ) 36.5 ( 1.5 ) 26.7 ( 1 ) 30 1300 ( 245 ) 40.3 ( 1.6 ) 28.7 ( 1.15 ) 34 2500 ( 475 ) 44.1 ( 1.5 ) 30.6 ( 1.2 ) 38 2900 ( 550 ) 47.9 ( 1.9 ) 32.5 ( 1.6 ) 42 4300 ( 815 ) 51.7 ( 2 ) 34.6 ( 1.4 ) 46 4700 ( 890 ) 55.5 ( 2.2 ) 36.7 ( 1.5 ) 50 5100 ( 970 ) 59.3 ( 2.4 ) 38.8 ( 1.6 ) 54 5500 ( 1045 ) 63.1 ( 2.5 ) 40.9 ( 1.6 ) 60 5900 (1120 ) 66.9 ( 2.7 ) 42.8 ( 1.7 )

PCA Measures at birth Measures afterwards Total 25 –28 468 225 693 29 – 31 1252 598 1850 32- 35 1092 518 1610 36 – 39 2494 1190 3684 40-42 2344 1118 3462 43- 60 1199 1199 Total 7650 4848 12498

PCA weeks BW g BL cm HC cm 25 686 ( 89 ) 35.3 ( 2.5 ) 25 ( 1.5 ) 26 860 ( 112 ) 36.2 ( 2.5 ) 25.6 ( 1.5 ) 30 1555 ( 202 ) 40 ( 2.8 ) 28 ( 1.7 ) 34 2250 ( 293 ) 43.8 ( 3 ) 30.5 ( 1.8 ) 38 2950 ( 384 ) 47.6 ( 3.3 ) 32.9 ( 1.97 ) 42 3645 ( 474 ) 51.4 ( 3.6 ) 35.3 ( 2.1 ) 46 4340 ( 564 ) 55.2 ( 3.9 ) 37.8 ( 2.25 ) 50 5035 ( 654 ) 59 ( 4.1 ) 40.2 ( 2.4 ) 54 5730 ( 745 ) 62.8 ( 4.4 ) 42.6 ( 2.55 ) 60 6775 ( 880 ) 68.5 ( 4.8 ) 46.3 ( 2.78 )

Brain: 15%

previous aspect of IUGR

Actual aspect of prematurity



In Growth retardation:

-

increase their hemoglobin;

-

Relative high cerebral mass;

-

Decrease of P-pyruvate kinase



In very low birthweight:

-

lower effect of insulin on glycogenesis and on

glycogenosis; these activities increase afer 34-40 w;

-

Limited gluconeogenesis;

-

Inappropriate ( in excess ) endogenous adrenergic



Is particular in very preterm babies



But also in case of cardiac dysfunction or

malformation



In case of NEC

Pt g

Lp g

Kcal

SGA

2.8-4

4.2-6

82

GA

TMR

BMR

Pt

24

82

35

3.42

1.43

28

84

38

3.40

1.54

32

86

41

3.38

1.65

36

88

44

3.36

1.76

40

90

47

3.34

1.87

44

92

50

3.32

1.98

%

Kcal

46

42

12

CH

11

88

1

Pt

60

23

17

120 6-8 120 6-8 Kcal/kg/d QO2 l/kg/m

50-60

60-70

%

carbohydrates

25-30

< 5

% Lipids

10-15

20-30

% Proteins



Proteins are the main component in

nutrition;



Even if proteins are done of aminoacids,

proteins and aminoacids need to be

considered in different ways;



Proteins turnover is linked to metabolic



Proteins have a central role in nutrition and in growth.

There is none storage, even if their turnover is high.

 d BW g/kg/d = 3.44 Pt intake g/kg/d + 7.34 ( Rahia, 1994 )  Pt needs g/kg/d = 3.5 – 0.00354 GA ( Rahia, 1994 )

 Pt synthesis = 0.0269 GA + O.785 ( Widdowson, 1977 )  Pt synthesis = 0.173 BMR – 2.56 ( Beaufrère, 1990 )

 d BW g = 3.6 Pt intake + 0.095 Energy intake – 0.0047 + 1.7 ( Heird, 1989 )  d PC = 0.1598 Pt intake + 0.253 ( Battisti, 1990 )

 d BL = 0.336 Pt intake + 0.253 ( Battisti, 1990 )

 Pt content % BW = 0.7 GA + 1.86 ( Widdowson, 1977 )  VO2 = 62 + 2 ml/kgProtein/min ( Battaglia, 1997 )

 Aminoacids coming from mother: the sources are her intakes

and her muscles;

 From these sources, 70 % go to the fetus and 20 % to the

placenta;

 [ Fetus / Mother ] AA ratio is 1.5 - 2

 Three types of transporters for AA in the placenta = A, L,

ASC;

 This transport is depending on delivery of O2 to the fetus;

when O2 delivery t the fetus decreases, AA delivery decreases also.



A :

and valine ), serine*, threonine*, gutamine* and alanine*;



L:

leucine, isoleucine,valine, phenylalanine;



ASC:

 * use the three types of transporters;

 Remember that «  fetal milk «  contains 25-30 % of AA,

60-70 % of carbohydrates ( glucose and lactate ) and less than 3 % of EFA; and that fetal milk is passing essentialy through the liver.



IQ global at 7.5 – 8 years= dBWg/kg/day + 84.5 ;



IQ verbal at 7.5 – 8 years = 1.29 dBW/kg/day + 79.

But also other parameters … ( i.e. head

 3 Purposes of that turnover:

- primary protection, - losses replacements,

- degradations of peptides;

 Within tissues:

in fetus and neonate, the proteins turnover is very high in the liver ( 50 % ) and in the brain ( 44 % );Proteins turnover is low in the other tissues ( in muscles= 3.2 % ).

These values are different in the adult: 57 % in liver, 50 % in kidney, 17 % in brain, 18 % in heart, 15 % in skeletal muscles.

 Within body:

proteins turnover is mainly represented by the muscles and intestines;

 _Overall

:

1 g tissue growth = 3 – 3.5 kcal; 0.086 g PT 0.105 G Lp;

 Protein synthesis:

is correlated to activities of hormones ( hGH, somatomedins, insulin , T4), to a caloric intake well proportionated and higher than 70 kcal/kg/d, and activities of skeletal muscles.

 The quantitative needs of proteins

can be estimated to values comprised between 2.5 ( TPN ) to 3.5 ( EN ) g/kg/d and these should be accompanied by 35 kcal/g of proteins;

 The qualitative needs of proteins

should contain 48 % essential AA ( mixture of casein and albumin ).

-

Weight in g

=175 PCA weeks – 3665 ( SD = 13 % )

Length in cm

= PCA weeks + 11 ( SD = 8 %)

HC in cm

= 0.6 PCA weeks + 10 ( SD = 6 % )

Corrected correlations in the assessment of Postnatal growth in premature babies



[ d W g / d HC cm ] per week

= 44 PCA – 1138 (SD = 13 %, r = 0.973) 



[ d L cm / d HC cm ] per week

 BW g without IUGR = 174 PCA – 3665 ( 13 % )  BW g with RCIU = 148 PCA – 3894 ( 18 % )  L cm = 0.95 PCA + 11.53 ( 7 % )  HC cm = 0.61 PCA + 9.72 ( 6 % )  LAC cm = 0.26 PCA – 1.685 ( 2% )  LAC / HC = 0.56 APCs + 6.5 ( 4% )  dWg / dL cm = 18.5 APCs – 404 ( 10 % )  dWg / dHCcm = 44 PCAs – 1138 ( 9.5 % )  dLcm / dHCcm = 0.094 APCs – 1.543 ( 6.5 % )  dHC cm = 0.1598 Pt in g/kg/j + 0.253  dLcm = 0.336 Pt in g/kg/j + 0.253

Ponderal index: only at birth

Body mass Index: only after 34 PCA

intakes AA = 25-30 % Glucose+lactate = 70 % Lip = essentials FA < 2 % Mean Mean values/week values/week dBWdBW_{= 170 g= 170 g} dBLdBL_{= 1 cm= 1 cm} dHC _{= 0.6 cm}dHC _{= 0.6 cm} < 30 w 145g 1.13 cm 0.9 cm 30-32 170 g 1.2 0.7 32-34 208 1.23 0.8 34-36 242 1 0.7 36-38 213 0.8 0.5 38-40 143 0.7 0.33 40-42 70 0.25 0.17

1 cm HC

1 g brain

1 g muscle

1 g weight

1 cm length

1 mm tsf

1 cm LAMC

 For length:

- dL cm = 0.587 +0.796 Ptin – 0.0888 CHin – 0.124 Lpin

( r=0.908)  82 %

- = 0.336 Ptin +0.253 (r=0.743)  49 %



For body weigth

:

- dW g = 243.44 + 12.06 CHin – 59.22 Ptin – 17.65 Lpin (r=0.852) - = 297.71 – 23.9 Lpin (r=0.793) _ 62 %

- = 4.744 Calin – 101.3 Ptin (r=0.608)  36 %



For head circumference

- dHC cm =0.2836 +0.244 Ptin + 0.0062 Lpin – 0.186 CHin (r=0.995)

 99 %

 Mother milk(not modified): CEPW = 10.5 (2.3) CEPL = 4 (1) CEPHC = 3.9 (0.5)  PT formula CEPW = 10.9 (4.3) CEPL = 4.8 (1.5) CEPHC = 3.3 (1)  T formula CEPW = 8.2 (3.3) CEPL = 5 (2.5) CEPHC = 3.4 (0.8) ns P < 0.05



Type of baby

Non growing growing

BMR

51.6 ( 2.3 )

64.5

( 4.9 )

CH %

66.6

( 2.5 )

80.2

( 4.6 )

Lp %

24.1

( 3.9 )

13 ( 5 )

Pt %

9.1 ( 2 )

6.6 ( 0.8 )

Conclusions:

Considering biochemical facts concerning different parameters of Growth:

There are charts for making a diagnosis at birth, Not all are equivalent, mainly for body weigth;

There are charts for postnatal growth,

but better are the relative indices for harmonious postnatal growth; In the postnatal growth, it is very important to be precise

About What tissues is being assessed