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A betamimetic drug and human fetal lung maturation
EUROP. J. OBSTET. GYNEC. REPROD. BIOL., 1979,9/4,261-263 0 ElseviedNorth-Holland Biomedical Press
A betamimetic drug and human fetal lung maturation L. Cabero, E. Giralt,
E. Navarro, J. Calaf, A. Cabero, P. Durban-Sgnchez and J. Esteban-Altirriba
Servicio de Obstetriciay Ginecologia, Hospital de la Santa Cruz y San Pablo, UniversidadAutonorm, Facultad de Medicina, Barcelona, Spain
Accepted for publication 28 February 1979 CABERO, L., GIRALT, E., NAVARRO, E., CALAF, J., CABERO, A., DURANSANCHEZ, P. and ESTEBAN-ALTIRRIBA, J. (1979): A betamimetic drug and human fetal lung maturation. Europ. J. Obstet. Gynec. reprod. BioZ.,9/4, 261-263. In a double-blind and randomized study the administration of a betamlmetic drug to the mother from week 33 to 35 produces a significant increase in amniotic fluid palmitic acid levels. We suggest that the administration of a betamimetic drug during pregnancy to the mother can be useful in producing an acceleration of the fetal lung maturation. lung maturity; palmitic acid; betamlmetic drugs
ritodrine (DU-21220) (10 mg 4 times per day per OS) was administered according to a randomized list in a double-blind manner, for 10 days from week 33 to 35. There were no ‘drop-outs’ in the study, and the groups were proved to be comparable for age, parity etc. (see Table I), Amniotic fluid (15 ml) was obtained by amniocentesis at the day of the onset and end of the treatment, the last amniocentesis taking place not later than 6 h after the last tablet. Pahnitic acid was determined in each sample by gas chromatography according to a previously described technique (Warren et al., 1973).
Introduction
In 1975 Boog et al. and in 1976 Cabero et al. reported on a decrease in the incidence of respiratory distress syndrome (RDS) in the group of babies whose mothers received betamimetic drugs during pregnancy when compared with those from the nontreated mothers. Those differences were higher, the lower the birth weight and the shorter the gestational age at delivery (Cabero et al., 1979). The purpose of the present study was to evaluate the differences in palmitic acid concentration in amniotic fluid when a betamimetic drug (ritodrine) was administered to the mother during normal pregnancy.
Results The results obtained are shown in Table I. The mean and one standard deviation of treated and control groups are expressed before and after treatment (Fig. 1).
Material and methods
Twenty normal pregnant women (reevaluated after delivery) volunteered for the study. Placebo or 261
262 TABLE I
L. Cabero et al.: A betamimetic drug and human fetal lung maturation Some clinic characteristics of patients and the results of palmitic acid levels in amniotic fluid (mg/lOO ml) Para
Age
Mother’s weight (kg)
Palmitic acid Before
Week delivery
Apgar test
After
Newborn’s weight (g)
neated 30 25 27 29 19 33 23 22 34 25
o-owl 2-o-O-2 l-04-1 o-o-O-0 O-O-O-0 o-O+0 O-O+0 O-O-O-O 3-O-2-2 o-O-O-0
66 65 85 59 76 62 68 60 77 60
0.15 0.17 1.31 0.29 0.50 0.40 0.64 0.75 0.83 1.49
1.79 1.72 2.18 1.31 1.17 0.71 2.15 3.61 1.79 1.85
2930 3650 4030 2950 3650 3210 3450 3530 3770 3570
39 40 41 38 41 40 42 41 39 40
9 9 8 9 9 7 7 8 8 8
10 10 10 10 10 10 10 10 10 10 910 10 10 10 10 10 10 10 10
Controls 23 25 28 20 23 32 32 28 22 28
o-O-O-0 O-O-O-O o-OJX! O-O-O-0 O-OGO 3-04-3 l-O-1-1 l-04)-1 l-O~)-1 o-o-O-0
61 60 62 53 56 70 59 73.5 65.8 71
0.50 1.30 1.29 1.47 0.75 1.10 1.53 0.43 0.40 0.60
0.60 1.60 0.86 1.70 1.05 1.45 1.70 0.33 0.70 1.20
2750 3150 3200 3050 2840 3050 3460 3250 3870 3680
40 40 41 41 36 38 39 40 41 41
9 8 8 9 4 8 9 7 9 9
10 10 10 10 10 10 10 10 810 10 10 10 10 10 10 10 10 10 10
The differences were evaluated with the Student t-test (Table II). In order to evaluate the normality in the distribution of the values obtained for each group, the Shapiro and Wilk test was used. As
m
TREATED
[7
PLACEBO
expected, there were no significant differences in the concentration of palmitic acid in amniotic fluid between both groups before treatment. The effects of the drug are reflected both in the differences between the groups after treatment and in the differences between the results before and after treatment in the ritodrine-treated group.
Comment
1;.I N?N.s xe HO&4 WEEK 33
WEEK 35
Fig. 1. Mean and standard deviations in treated and placebo groups before and after treatment and statistical study of differences.
According to the results, it can be suggested that the betamimetic drug used is able to produce a significant increase in amniotic fluid palmitic acid levels, reflecting an acceleration in fetal lung maturity. In an experimental study conducted in rabbits, our group observed an acceleration in fetal lung maturation as a response to another betamimetic agent (orciprenaline) (Cabero et al,, 1977). The mechanism by which the drug exerts its influence is still unknown. In conclusion, we consider it possible to suggest
L. Cabero et al.: A betamimetic drug and human fetal lung maturation TABLE II
Statistical study of the differences between groups by Student I-test Week 33
Treated Controls
263
Week 35
n
x
SD
n
x
SD
10 10
0.653 0.981
0.456 0.412
10 10
1.820 1.119
0.712 0.490
1 = 1.730 2P NS
t
2P
4.1193 0.5209
P < 0.001 NS
t = 2.4229 P < 0.05
n = number of cases; X = mean; SD = standard deviation; NS = not significant.
that betamimetic drugs can be useful in the medical acceleration of fetal lung maturation in normal pregnant women.
References Boog, G., Ben Brahim, M. and Gandar, R. (1975): Betamimetic drugs and possible prevention of respiratory distress. Brir. J. Obstet. Gynaec., 82, 285-288. Cabero, L., Quilez, M., Escribano, I., Calaf, J., Giralt, E., Dur&%nchez, P. and Esteban-Altirriba, J. (1976): Sindrome de distress respiratorio neonatal en cases de
amenaza de parto prematuro tratados con betamim8ticos. Clin. Invest. Obstet. Ginec., 3, 169-171. Cabero, L., Alemany, J.R.,Qui’lez, M., Riera, R., Navarro, E., Tomer, A., Dunin-SQnchez, P. and Esteban-Altirriba, J. (1977): Orciprenaline and fetal lung maturation in rabbits. Europ. J. Obstet. Gynec. reprod. Biol., 7, 351358. Cabero, L., Escribano, I., Siez, J., Calaf, J., DurinStichez, P. and Esteban-Altirriba, J. (1979): Neonatal respiratory distress syndrome in cases of premature labour treated by betamimetic drugs. Submitted to: Europ. J. Obstet. Gynec. reprod. Biol. Warren, C., Allen, J.T. and Holton, J.B. (1973): Assessment of foetal lung maturity by amniotic fluid fatty acid analysis. Clin. chim. Acra, 44, 457-459.
A betamimetic drug and human fetal lung maturation L. Cabero, E. Giralt,
E. Navarro, J. Calaf, A. Cabero, P. Durban-Sgnchez and J. Esteban-Altirriba
Servicio de Obstetriciay Ginecologia, Hospital de la Santa Cruz y San Pablo, UniversidadAutonorm, Facultad de Medicina, Barcelona, Spain
Accepted for publication 28 February 1979 CABERO, L., GIRALT, E., NAVARRO, E., CALAF, J., CABERO, A., DURANSANCHEZ, P. and ESTEBAN-ALTIRRIBA, J. (1979): A betamimetic drug and human fetal lung maturation. Europ. J. Obstet. Gynec. reprod. BioZ.,9/4, 261-263. In a double-blind and randomized study the administration of a betamlmetic drug to the mother from week 33 to 35 produces a significant increase in amniotic fluid palmitic acid levels. We suggest that the administration of a betamimetic drug during pregnancy to the mother can be useful in producing an acceleration of the fetal lung maturation. lung maturity; palmitic acid; betamlmetic drugs
ritodrine (DU-21220) (10 mg 4 times per day per OS) was administered according to a randomized list in a double-blind manner, for 10 days from week 33 to 35. There were no ‘drop-outs’ in the study, and the groups were proved to be comparable for age, parity etc. (see Table I), Amniotic fluid (15 ml) was obtained by amniocentesis at the day of the onset and end of the treatment, the last amniocentesis taking place not later than 6 h after the last tablet. Pahnitic acid was determined in each sample by gas chromatography according to a previously described technique (Warren et al., 1973).
Introduction
In 1975 Boog et al. and in 1976 Cabero et al. reported on a decrease in the incidence of respiratory distress syndrome (RDS) in the group of babies whose mothers received betamimetic drugs during pregnancy when compared with those from the nontreated mothers. Those differences were higher, the lower the birth weight and the shorter the gestational age at delivery (Cabero et al., 1979). The purpose of the present study was to evaluate the differences in palmitic acid concentration in amniotic fluid when a betamimetic drug (ritodrine) was administered to the mother during normal pregnancy.
Results The results obtained are shown in Table I. The mean and one standard deviation of treated and control groups are expressed before and after treatment (Fig. 1).
Material and methods
Twenty normal pregnant women (reevaluated after delivery) volunteered for the study. Placebo or 261
262 TABLE I
L. Cabero et al.: A betamimetic drug and human fetal lung maturation Some clinic characteristics of patients and the results of palmitic acid levels in amniotic fluid (mg/lOO ml) Para
Age
Mother’s weight (kg)
Palmitic acid Before
Week delivery
Apgar test
After
Newborn’s weight (g)
neated 30 25 27 29 19 33 23 22 34 25
o-owl 2-o-O-2 l-04-1 o-o-O-0 O-O-O-0 o-O+0 O-O+0 O-O-O-O 3-O-2-2 o-O-O-0
66 65 85 59 76 62 68 60 77 60
0.15 0.17 1.31 0.29 0.50 0.40 0.64 0.75 0.83 1.49
1.79 1.72 2.18 1.31 1.17 0.71 2.15 3.61 1.79 1.85
2930 3650 4030 2950 3650 3210 3450 3530 3770 3570
39 40 41 38 41 40 42 41 39 40
9 9 8 9 9 7 7 8 8 8
10 10 10 10 10 10 10 10 10 10 910 10 10 10 10 10 10 10 10
Controls 23 25 28 20 23 32 32 28 22 28
o-O-O-0 O-O-O-O o-OJX! O-O-O-0 O-OGO 3-04-3 l-O-1-1 l-04)-1 l-O~)-1 o-o-O-0
61 60 62 53 56 70 59 73.5 65.8 71
0.50 1.30 1.29 1.47 0.75 1.10 1.53 0.43 0.40 0.60
0.60 1.60 0.86 1.70 1.05 1.45 1.70 0.33 0.70 1.20
2750 3150 3200 3050 2840 3050 3460 3250 3870 3680
40 40 41 41 36 38 39 40 41 41
9 8 8 9 4 8 9 7 9 9
10 10 10 10 10 10 10 10 810 10 10 10 10 10 10 10 10 10 10
The differences were evaluated with the Student t-test (Table II). In order to evaluate the normality in the distribution of the values obtained for each group, the Shapiro and Wilk test was used. As
m
TREATED
[7
PLACEBO
expected, there were no significant differences in the concentration of palmitic acid in amniotic fluid between both groups before treatment. The effects of the drug are reflected both in the differences between the groups after treatment and in the differences between the results before and after treatment in the ritodrine-treated group.
Comment
1;.I N?N.s xe HO&4 WEEK 33
WEEK 35
Fig. 1. Mean and standard deviations in treated and placebo groups before and after treatment and statistical study of differences.
According to the results, it can be suggested that the betamimetic drug used is able to produce a significant increase in amniotic fluid palmitic acid levels, reflecting an acceleration in fetal lung maturity. In an experimental study conducted in rabbits, our group observed an acceleration in fetal lung maturation as a response to another betamimetic agent (orciprenaline) (Cabero et al,, 1977). The mechanism by which the drug exerts its influence is still unknown. In conclusion, we consider it possible to suggest
L. Cabero et al.: A betamimetic drug and human fetal lung maturation TABLE II
Statistical study of the differences between groups by Student I-test Week 33
Treated Controls
263
Week 35
n
x
SD
n
x
SD
10 10
0.653 0.981
0.456 0.412
10 10
1.820 1.119
0.712 0.490
1 = 1.730 2P NS
t
2P
4.1193 0.5209
P < 0.001 NS
t = 2.4229 P < 0.05
n = number of cases; X = mean; SD = standard deviation; NS = not significant.
that betamimetic drugs can be useful in the medical acceleration of fetal lung maturation in normal pregnant women.
References Boog, G., Ben Brahim, M. and Gandar, R. (1975): Betamimetic drugs and possible prevention of respiratory distress. Brir. J. Obstet. Gynaec., 82, 285-288. Cabero, L., Quilez, M., Escribano, I., Calaf, J., Giralt, E., Dur&%nchez, P. and Esteban-Altirriba, J. (1976): Sindrome de distress respiratorio neonatal en cases de
amenaza de parto prematuro tratados con betamim8ticos. Clin. Invest. Obstet. Ginec., 3, 169-171. Cabero, L., Alemany, J.R.,Qui’lez, M., Riera, R., Navarro, E., Tomer, A., Dunin-SQnchez, P. and Esteban-Altirriba, J. (1977): Orciprenaline and fetal lung maturation in rabbits. Europ. J. Obstet. Gynec. reprod. Biol., 7, 351358. Cabero, L., Escribano, I., Siez, J., Calaf, J., DurinStichez, P. and Esteban-Altirriba, J. (1979): Neonatal respiratory distress syndrome in cases of premature labour treated by betamimetic drugs. Submitted to: Europ. J. Obstet. Gynec. reprod. Biol. Warren, C., Allen, J.T. and Holton, J.B. (1973): Assessment of foetal lung maturity by amniotic fluid fatty acid analysis. Clin. chim. Acra, 44, 457-459.