Blood pressure in very low birth weight infants in the first 70 days of life

26 6

Higashi et al.

REFERENCES 1. Dauncey M J, Shaw JCL, Urman J. The absorption and retention of magnesium, zinc and copper by low birth weight infants fed pasteurized human breast milk. Pediatr Res 1977;11:991-7. 2. Casey CE, Hambidge KM. Trace minerals. In: Tsang RC, ed. Vitamin and mineral requirements in preterm infants. New York: Marcel Dekker, Inc., 1985:153-84. 3. Mendelson RA, Bryan MH, Anderson GH. Trace mineral balances in preterm infants fed their own mother's milk. J Pediatr Gastroenterol Nutr 1983;2:256-61. 4. Higashi A, Matsuda I, Masumoto T, Saikusa H, Yabuso M, Oka Y. Serum zinc and copper concentration in low birth weight infants during first three months of life: correlation to birth weight and different feedings. Tohoku J Exp Med 1985;146:253-63. 5. Di Tore R, More C, Perrone L, et al. Postnatal dependence of plasma copper and zinc levels on gestational age and maturity observed in infants fed a high zinc content formula. J Pediatr Gastroenterol Nutr 1985;4:756-61. 6. Matsuda I, Higashi A, Ikeda T, Uehara I, Kuroki Y. Effects of zinc and copper content of formulas on growth and on the concentration of zinc and copper in serum and hair. J Pediatr Gastroenterol Nutr 1984;3:421-51. 7. Lubchenco LO, Hansman C, Dresslen M, Boyd E. Intrauterine growth as estimated from live born birth weight data at 24 to 42 weeks of gestation. Pediatrics 1963;32:793-800. 8. Dubowitz LMS, Dubowitz V, Goldberg C. Clinical assessment of gestational age in the newborn infant. J PEDIATR 1970;77:1-10.

The Journal of Pediatrics February 1988

9. Higashi A, Ikeda T, Uehara I, Matsuda I. Effect of low zinc and copper content formula on infant nutrition. Eur J Pediatr 1982; 138:237-40. 10. Ehrenkranz RA, Aekerman BA, Nelli CM, Janghorbani M. Determination with stable isotopes of the dietary bioavailability of zinc in premature infants. Am J Clin Nutr 1984;40:7281. 11. Voyer M, Davakis M, Antenner I, Valleur D. Zinc balances in preterm infants. Biol Neonate 1982;42:87-92. 12. Hambidge KM, Casey CE. Trace element requirements in premature infants. In: Lebenthal E, ed. Textbook of gastroenterology and nutrition in infancy. New York: Raven Press, 1981:595-610. 13. Morris FH Jr. Trace minerals. Semin Perinatol 1979;3:36979. 14. Matsuda I, Higashi A. Survey of zinc and copper deficiency in Japan. J Jpn Pediatr Soc 1983;87:710-6. 15. Shaw JC. Trace elements in the fetus and young infant. I. Zinc Am J Dis Child 1979;133:1260-8. 16. Windowson EM, Dancey J, Shaw JCL. Trace elements in fetal and early postnatal development. Proc Nutr Soc 1974;33:275-84. 17. Tyrala E. Zinc and copper balances in preterm infants. Pediatrics 1986;77:513-7. 18. Joint Food and Agriculture Organization/World Health Organization Food Standards Programme. Recommended international standards for foods for infants and children. Rome: Food and Agriculture Organization/World Health Organization, 1976.

Clinical and laboratory observations Blood pressure in very low birth weight infants in the first 70 days of life K. L. Tan, MBBS, FRCPE From the Department of Pediatrics, National University of Singapore, and the Neonatal Unit, Kandang Kerbau Hospital, Singapore

T h o u g h m e a s u r e m e n t s of blood pressure in newborn infants have been recorded in the early hours of life, 1 only two studies, one of daily systolic pressure with no diastolic Submitted for publication June 2, 1987; accepted Aug. 21, 1987. Reprint requests: K. K. Tan, MBBS, FRCPE, Department of Pediatrics, Kandan Kerbau Hospital, Hamshire Rd., Singapore 0821, Republic of Singapore.

pressure or m e a n arterial pressure s a n d another with systolic BP, diastolic BP, a n d M A P of h e a l t h y full-term newborn infants in the first 6 days of life, have been BP MAP PCV VLBW

Blood pressure Mean arterial pressure Packed cell volume Very low birthweight

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reported. 3 Similarly, very little has been documented regarding the BP of preterm very low birth weight infants, except for a study of such infants over the first 4 weeks of life.4 It was therefore thought worthwhile to study the BP of preterm VLBW infants for the first 10 weeks of life. The present report is a result of such a study. METHODS Preterm VLBW infants (gestational age <34 weeks, birth weight <1500 g) were studied. All the infants had to fulfill the following criteria: Apgar score >4 at 1 minute and >6 at 5 minutes, and no evidence of respiratory distress, sepsis, central depression, or cerebral irritation. If any complication occurred in an infant during the course of the study (e.g., septicemia, bronchopneumonia, patent ductus arteriosus), thatinfant was removed from the study group. A complete blood cell count, including hemoglobin and packed cell volume determination, was performed on the first, third, and seventh days of life and weekly thereafter. BP measurements were made with the osr technique (Dinamap monitor, Critikon, Inc., Tampa, Fla.), which has been demonstrated to be reliable,s's this being confirmed before the study by intraarterial (umbilical) pressure measurements. All the measurements were made in the morning (0900 to 1100 hours) and in the afternoon (1500 to 1630 hours) with the infants awake and asleep. "Sleep" was defined as a state in which the infant had the eyes closed, was quiet, and was breathing either regularly or periodically but with no apnea; "wakefulness" was defined as a state in which the infant had the eyes open, either constantly or intermittently, but remained quiet and still. The measurements were made with the Dinamap oseillometric monitor and cuff sizes were based on the limb circumference, as recommended by the manufacturer; for this study, cuff sizes 2, 3, and 4 (bladder width 2.8, 3.8, and 4.6 cm, respectively) were used. The measurements were made on both upper arms and the right lower limb (calf) in duplicate, with the infant lying supine. The mean of the two readings was recorded; if any movement occurred during the reading, or if the duplicate measurements demonstrated a divergence >4 mm Hg, the whole procedure was repeated. Measurements were made d a i l y during the first 7 days, on days 10 and 14, and subsequently weekly for the first 10 weeks of life. All the infants were nursed in the premature nursery during the period of the study. Comparisons of significance between BP values were made with the paired Student t test. The BP values in relation to the other measurements studied were also examined with the Pearson correlation.

Clinical and laboratory observations

267

RESULTS Initially, 70 preterm infants were enrolled in the study. Complications of patent ductus arteriosus (9 infants), septicemia (8), prolonged intravenous therapy (4), and late respiratory illnesses (4) reduced the number in the study to 20 male and 25 female infants (birth weight 1221.8 + 171.4 [mean _+ SD] and gestational age 31.7 _+ 3.1 weeks). Twenty of the 45 infants initially required dextrose (5% or 10%) infusion, followed by premature formula (Pre-Nan, Nestle, Vevey, Switzerland) given orally, within the first 24 hours of life; the infusion was discontinued by the fourth day of life. The remaining 20 infants were started on oral formula within the first 6 hours of life. Fluid intake after 3 days ranged from 160 to 200 ml/kg body weight per day; adequate hydration was maintained. The BP and heart rate of infants <1250 g (25 infants) were almost identical to those of infants >_ 1250 g throughout the study. Hence it was decided to evaluate the data as a whole. The right upper limb systolic BP in the morning during the waking state (Table) increased initially to peak on the fourth day of life, before gradually declining to reach a nadir on the tenth day; thereafter a gradual increase was observed until the end of the study period. This same trend was observed with the diastolic and mean BPs. No significant difference between sleeping and waking BPs could be detected. The afternoon BP was also similar to the morning BP during the waking and sleeping states. The difference in BP values on consecutive days was too small to be significant, However, the fourth day's peak BP was significantly higher than the starting systolic BP (t = 3.07, P <0.01), diastolic BP (t -- 3.36, P <0.01), and M A P (t = 2.53, P <0.02); the BP values at the nadir on the tenth day were not significantly higher than the first-day values. However, the result of subsequent gradual rise in BP values was that the final BP on the day 70 was significantly higher than the nadir systolic BP (t -- 3.37, P <0.01), diastolic BP (t = 2.55, P <0.02), and M A P (t = 2.39, P <0.02). The waking and sleeping heart rates were similar; no correlation between BP and heart rate was observed for any day. There was no definite trend in heart rate over the whole study period; however, a similarity in the pattern of change with increasing age between heart rate and BP could be observed. It resulted in a significant correlation between heart rate and systolic BP during the waking state for the first 42 days of life (r = 0.62, P <0.02), but not between the heart rate and diastolic BP (r -- 0.25, 1.0 > P >0.1) or MAP (r = 0.14, 1.0 > P >0.1). No correlation could be demonstrated between the sleeping BP and heart rate. As the PCV and hemoglobin values declined with age

268

Clinical and laboratory observations

The Journal of Pediatrics February 1988

Table. Right upper arm morning BP and heart rate, and PCV, hemoglobin, and weight, in the first 10 weeks of life Days I

2

4

5

6

Mean (2 SD) Mean (2 SD)

67.9 (30.8) 65.0 (27.2)

71.9 (33.6) 72.0 (33.0)

74.3 (31.4) 77.0 (31.4)

77.5 (37.0) 71.0 (41.2)

74.2 (29.2) 74.8 (27.2)

76.8 (31.0) 76.9 (33.8)

76.2 (29.6) 73.7 (27.0)

Mean (2 SD) Mean (2 SD)

43.5 (28.8) 41.4 (24.6)

48.3 (30.2) 48.9 (31.0)

49.3 (31.6) 52.7 (32.0)

52.5 (31.8) 50.7 (28.2)

49.0 (28.6) 49.3 (26.8)

51.8 (30.0) 53.0 (33.0)

47.6 (27.2) 46.7 (25.4)

Mean (2 SD) Mean (2 SD)

57.7 (31.8) 55.8 (27.2)

59.6 (29.6) 60.9 (31.0)

63.7 (30.2) 64.8 (34.2)

65.0 (35.4) 62.6 (30.0)

61.9 (31.6) 61.7 (28.2)

63.5 (30.8) 64.4 (33.6)

63.5 (28.4) 61.0 (28.4)

Mean (2 SD) Mean (2 SD)

169.2 (63.2) 177.5 (67.8)

164.6 (78.4) 173.1 (77.2)

167.2 (64.4) 169.1 (61.0)

173.2 (66.8) 176.4 (69.6)

169.2 (50.2) 166.3 (56.0)

172.9 (57.2) 173.1 (54.2)

170.9 (60.8) 168.9 (74.2)

PVC (%)

Mean (2 SD)

61.0 (18.2)

53.7 (21.2)

50.8 (16.8)

Hb (g/dL)

Mean (2 SD)

20.2 (6.0)

17.9 (7.0)

17.0 (5.2)

Wt (g)

Mean (2 SD)

1221.8 (342.8)

1171.1 (314.0)

1155.2 (382.8)

Systolic pressure

Awake Asleep

Diastolic pressure

Awake Asleep

Mean arterial pressure

Awake Asleep

Heart rate

Awake Asleep

3

7

Hb, hemoglobin.

(Table), the BP values gradually increased. During the waking state, a negative correlation was observed between the PCV and systolic BP ( r - - - 0 . 8 4 , P <0.001) and diastolic BP (r = - 0 . 8 1 , P <0.01), but not between the PCV and MAP (r = -0.56, 0.1 > P >0.05); this correlation (including MAP) was also seen during sleep (r = -0.81, P <0.01; r = -0.67, P <0.02; and r = -0.71, P <0.01, respectively). Moreover, when the PCV and pulse pressure were examined, a negative correlation was again demonstrated over the whole study period for both the waking state (r -- -0.78, P <0.01) and the sleeping state (r = -0.71, P <0.01). Although no correlation between body weight and BP for any particular day could be observed, the pattern of weight increment appeared to be similar to that of BP increase. A positive correlation over this study period could be demonstrated between weight and BP during the waking state for the systolic BP (r = 0.91, P <0.001), diastolic BP (r = 0.89, P <0.001), and M A P (r = 0.72, P <0.01), as well as during sleep (r = 0.67, P <0.02; r - - 0 . 8 6 ; P <0.001; and r - - 0 . 8 4 , P <0.001, respectively). The respective BP values for both upper and right lower

extremities were similar, asleep and awake, and in the morning and afternoon. DISCUSSION In only one previous report of BP values in preterm VLBW infants was the oscillometric method identified4; the values over the 4 weeks covered in that report were lower than those documented herein, with the difference becoming less with increasing age. The reason for this discrepancy is not clear; however, the infants in the present study were in a stable state during the whole period studied. After the initial peak at the mid point of the first week, followed by a gradual decline until the mid point of the second week of life, a steady increase in BP values was observed for the remainder of the 10 weeks. The higher waking BP values (compared with the sleeping BP values) reported in previous studies in full-term infants 3,9,1~ (although not significantly higher at the end of the first week 3) were not observed in the present study; the BP values during waking and sleeping states were very similar. These infants were immature and showed little difference in physical activities during the waking and sleeping states

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Clinical and laboratory observations

269

Days 40

44

21

56

63

70

72.8 (30.6) 74.7 (32.2)

75.7 (32.0) 70.9 (26.0)

76.2 (31.6) 75.5 (31.6)

78.0 (33.6) 80.8 (37.0)

28

78.1 (34.2) 75.9 (32.6)

35

80.3 (32.4) 83.5 (33.6)

85.2 (37.2) 86.2 (38.0)

86.0 (40.6) 86.7 (36.0)

83.9 (32.0) 79.9 (40.4)

90.8 (36.2) 88.6 (38.6)

46.7 (27.8) 50.0 (30.2)

45.8 (31.2) 45.2 (22.4)

48.8 (31.6) 48.8 (29.8)

48.7 (30.8) 50.9 (34.6)

50.4 (29.2) 48.5 (29.8)

50.4 (32.4) 51.0 (32.6)

53.3 (31.2) 50.8 (30.4)

51.9 (35.8) 52.3 (32.4)

51.8 (32.6) 52.1 (38.6)

55.3 (33.8) 59.3 (32.0)

59.2 (30.4) 59.9 (28.4)

58.1 (32.2) 55.1 (24.2)

60.2 (32.0) 60.1 (29.6)

65.0 (33.6) 64.7 (37.0)

63.4 (32.4) 60.6 (29.2)

63.0 (34.0) 66.6 (33.6)

60.2 (40.0) 66.6 (35.8)

69.4 (36.0) 67.4 (37.6)

66.3 (34.4) 63.7 (34.0)

70.9 (35.2) 72.0 (36.2)

173.8 (59.8) 173.1 (60.8)

173.4 (56.2) 172.8 (61.8)

174.1 (49.8) 172.8 (63.4)

173.7 (47.4) (170.9 (39.8)

172.7 (42.4) 169.7 (43.8)

177.3 (44.4) 178.3 (42.0)

169.5 (51.8) 166.0 (41.0)

168.1 (44.4) 167.7 (40.4)

166.9 (48.6) 176.7 (38.6)

166.9 (48.2) 169.4 (34.0)

45.5 (17.4)

40.6 (17.0)

36.1 (13.6)

35.i (10.6)

34.2 (11.0)

35.1 (12.4)

32.6 (10.2)

31.9 (9.4)

32.1 (13.2)

14.7 (5.0)

13.3 (4.6)

12.1 (4.6)

11.8 (4.0)

11.5 (4.0)

11.5 (4.6)

10.8 (3.4)

10.6 (2.8)

11.I (3.0)

1217.3 (402.0)

1324.7 (508.2)

1467.9 (575.6)

1591.2 (696.8)

1819.7 (846.2)

1969.0 (949.4)

2134.1 (1095.6)

2273.8 (1420.4)

2525.3 (1306.8)

over the 10 weeks of study. The further observation of a similar heart rate during both states also tended to support this impression. However, correlation between heart rate and BP could be demonstrated only with the waking systolic BP, and that only for the first 42 days of life. The BP values in the upper and lower limbs appeared similar over the 10 weeks of study, contrary to some reports. H,~2 This reported difference with the Doppler method is most likely the result of differences in extremity circumference, not the site of measurements) 3 The present study, demonstrating similarity of BP values in both upper and lower limbs over a period of 10 weeks, might appear surprising. However, the infants spent almost the entire duration of this period in the horizontal position, thus largely eliminating the effect of differential gravity on the BP values. At the end of this study, the infants were about the same stage of life as full-term infants 1 week old, in whom no difference between upper and lower limb BP, or between sleeping and waking BP, has been observed) A gradual but definite progressive rise in BP could be observed from the second week of life onward. The BP at 10 weeks of age was significantly higher than that at the start or at the second week of life and was also substantial-

42

49

ly higher than that of full-term infants of 1 weeks of age3; only at 4 weeks of age did full-term infants attain comparable systolic BP values. 14 The reason is not clear. Perhaps the earlier exposure to the extrauterine form of circulation, with its greater systemic resistance, and the change of environment from the state of weightlessness in utero to that of the "weighted down" situation ex-utero, are important factors in determining this phenomenon. The increase in weight, which directly correlated with the BP increase for the duration of the study, may also play a role in early extrauterine life; the larger blood volume, with the presumably correspondingly greater effort required to circulate the blood effectively, may also be an additional factor. The increasing anemia, which also correlates directly with the BP rise and the pulse pressure, could also be a further enhancing factor; however, no significant change in heart rate occurred, as might have been expected. Indeed, BP levels of full-term infants also increase steadily until 6 weeks of age, before remaining fairly steady until 1 year of age. t5 I am grateful to Dr T. S. Koh, Medical Director of Kandang Kerbau Hospital, for permission for this study, Prof. H. B. Wong

270

Clinical and laboratory observations

for encouragement, L. S. Tan for the figures, and L. E. Lee and the nursing personnel for enthusiastic cooperation.

REFERENCES 1. Kitterman JA, Phibbs RH, Tooley WH. Aortic blood pressure in normal newborn infants during the first 12 hours of life. Pediatrics 1969;44:959-68, 2. De Swiet M, Fancourt R, Peto J. Systolic blood pressure variation during the first 6 days of life. Clin Sci Molec Med i975;49:557-61. 3. Tan KL. Blood pressure in full-term healthy neonates. Clin Pediatr 1987;26:21-4. 4. Ingelfinger JR, Powers L, Epstein MF. Blood pressure norms in low birth weight infants: birth through four weeks [abstract]. Pediatr Res 1983;17:319. 5. Ramsey M I I I . Noninvasive automatic determination of mean arterial pressure. Med Biol Eng Comput 1979;17: 11-8. 6. Nelson NM. On the indirect determination of systolic and diastolic blood pressure in the newborn infant. Pediatrics 1968;42:934-41. 7. Kimble K, Darnell RA, Yelderman M, Ariagno RL, Ream AK. An automated oscillometric technique for estimating mean arterial pressure in critically ill infants. Anesthesiology 1981;54:423-5.

The Journal of Pediatrics February 1988

8. Frieson RH, Lichtor JL. Indirect measurement of blood pressure in neonates and infants utilizing an automatic noninvasive oscillometric monitor. Anesth Analg 1981; 60:742-6. 9. Earley A, Pagers P, Ng S, Shinebourne EA, De Swiet M. Blood pressure in the first 6 weeks of life. Arch Dis Child 1980;55:755-7. 10. Lee YH, Rosner B, Gould JB, Kars EH. Familial aggregation of blood pressure of infants and their mothers. Pediatrics 1976;58:722-9. l 1. De Swiet M, Peto J, Shinebourne EA. Difference between upper and lower limb pressure in neonates using Doppler technique. Arch Dis Child 1974;49:734-5. 12. Goldring D, Wohltmann H. Flush method for blood pressure determination in newborn infants. Pediatrics 1958;21:950-7. 13. Lum LG, Jones MO. The effect of cuff width on systolic blood pressure measurements in neonates. J PEDIATR 1977;91: 963-6. 14. Earley A, Eryers P, Ng S, Shinebourne EA, De Swiet M. Blood pressure in the first 6 weeks of life. Arch Dis Child 1980;55:755-7. 15. De Swiet M, Fayers P, Shinehourne EA. Systolic blood pressure in a population of infants in the first year of life: The Brompton Study. Pediatrics 1980;65:1028-35.