5 neonatal intraventricular hemorrhage (ivh) following maternal beta-sympathomimetic tocolysis

1
Volume 166 1, Part 2 5 NEONATAL INTRAVENTRICULAR HEMORRHAGE (IVH) FOLLOWING MATERNAL BETA-SYMPATHOMIMETIC TOCOLYSIS, LJ Groome, RL Goldenberg, SP Cl i ver,' RO Davi s, RL Copper,' University of Alabama Hospitals, Birmingham, Alabama There has not been a reduction in neonatal morbidity or morta 1 ity associ ated with the wi despread use of B-mimet i c agents (BMA) to delay delivery, An increase in the incidence of IVH following B-mimetic tocolysis may be partly responsible for this lack of improvement even if delivery ;s delayed. This study was designed to determine if the incidence of IVH is increased in the offspri ng of women who recei ved a BMA for preterm 1 abor tocolysis. The population consisted of women who delivered singleton liveborn infants free of neurological anomalies at 25- 36 weeks during a multicenter preterm birth prevention trial (1982-86). Based on factors such as gestational age and cervical dilatation, women in preterm labor were either not treated, given magnesium sulfate (MgSO.) or received a BMA. IVH was di agnosed by ultrasound, rout i ne 1y performed on infants <1500 gms and as indicated at higher weights. Of the 1978 infants wi th ei ther spontaneous preterm 1 abor or PROM who del ivered preterm, 105 (5.3%) had IVH and 32 (1.6%) had grade III or IV IVH. Use of a BMA was associated with a 4-fold increase in the incidence of IVH compared to the use of either MgSO, or no toea 1 yt i c agent (p<O, 001). In vi rtua 11 y all preterm gestational age groups, there was a 2-fold and generally significant increase in the incidence of IVH following BMA tocolysis. A logistic regression analysis was performed 'adjusting for the type of tocolytic agent, gestational age at delivery, birthweight, medical center, route of delivery, indication for delivery, race, infant sex, and respiratory di st ress syndrome. The use of a BMA was found to be significantly associated with IVH [Ddds Ratio (OR) of 2,3 (1.23- 4.29)]. In addition, BMA tocolysis was associated with a significant increase in the incidence of grades III and IV IVH when compared to no treatment [OR of 2,91 (I ,06-7,97)], This retrospective study suggests that BMA tocolytic therapy may be associated with at least a 2-fold increase in the incidence of IVH even when other ri sk factors are taken; nto account. 6 THE CANADI AN MULTI CENTRE ReT OF EARLY AMNI OTOMY, WD FraserX, S Marcoux X , JM Moutqui D, A Chri steo X , BA Armson, JP Verreaul tX, N OkunX, C Ni mrod, AK Joshi x, H Cohen, L Bayer, T DoranX, P Bernstei 0, J Carfo) ) x, 5 Bottoms, F Gal Elroeau X , Laval Uni versi t y, Qu{'bec, Canada. The goal of the study was to determine if a policy 01 earl y amni otomy for null i parae in tE'rm spontaneous labour is an effecti ve means to prevent dystoci a. In 11 centres, 925 W'Omen were randoml y aJ J ocatEld to either early amniotomy (ARM) or to conservation of the membranes (COM). For thE' purpose of thE' study, dystoci a was defi ned as a peri od of at I east 4 hours, after 3 cpnti meters di) atati on bad been achi ved, duri ng "'hi ch the mean rate of cervi cal di I atati on was -( 0.5 em/hr. Treatment groups were SI mi I ar wi th respect to age, GA, years of educati on, wei gbt, cervi cal status, and baby's bi rthwei ght. The medi an interval from faDdomi zati on to membrane rupture was 20 mi n. in t be ARM group and 230 mi n. in t he COM group. Epi dural anesthesi a and el ectroni c fetal moni tori ng were used wi th sl mi I ar frequency in the two groups. Oxytoci n was used pri or to a di agnosi s of dystoci a in a similar proportion of women in the two groups (ARM- 13.2%; COM - 11. 4%). Dystoci a was Jess frequent in the ARM group than in the COM group (33.6% VS 44.6%; p = 0.001). The mean interval from randomi zati on to del i very for women del i veri ng vagi nail y was approxi mate) y 1. 5 hours shorter j n t be ARM than j n the- cOMgroup (p -( 0.0001). The distribution of modes of del i ver y was si mi I ar j n the two groups. Groups were also comparable with respect to indicators of neonatal status (APGAR 5 -< 7, arterial cord pH -( 7.20, admi 55i on to I CU, cephal ohematoma). Thus, a pol i cy of earl y amni otomy was found to be protecti ve for dystocia by the study definition (RR = 0.75). SPO Abstracts 275 7, EXPRESSION OF PARATHYROID HORMONE-RELATED PEPTIDE (PTHrP) mRNA IN PLACENTAL MEMBRANES AND AMNIOTIC FLUID (AF). Ferguson II JE, Gorman JX, Bruns DEx, Pandian MRx,+, Bruns MEHx, Departments of Obstetrics and Gynecology and Pathology, University of Virginia School of Medicine, Charlottesville, VA, and +Nichols Institute, San Juan Capistrano, CA PTHrP was originally discovered in human tumors that produce hypercalcemia of malignancy, The hormone increases cyclic AMP and prostaglandin E2 in target tissues, but its physiological functions are unknown, We previously reported that PTHrP mRNA is expressed in laboring human uterus. We here report the unexpected finding that PTHrP is abundantly expressed in human amnion and reaches high concentrations in amniotic fluid, PTHrP mRNA was measured by computer-aided densitometry of Northern blot autoradiographs, The hormone was measured by use of a sandwich immunoassay. PTHrP mRNA abundance was 5-15 times that found in myometrium and exceeded that found even in lactating mouse mammary gland, the richest source previously identified, PTHrP mRNA abundance was decreased by 60% (p<0,025) in amnion from laboring (n=16) vs, non-laboring (n=16) women. The concentration of PTHrP in AF equaled or exceeded those found in serum of patients with hypercalcemia of malignancy, The mean concentrations of hormone in AF at 16 and 39 weeks were 21 ± 6 and 38 ± 11 pmol/L, respectively, These data suggest that the amnion sustains regulated abundant expression of PTHrP; the high concentrations of PTHrP in AF suggest an important role of PTHrP in normal pregnancy, 8 COMPARISON OF INDUCTION METHODS FOR PREMATURE RUPTURE OF MEMBRANES AT TERM. J,F, McCaul, L,M, Wi11iams,x R,W, Martin, E,F, Magann,X [, Gallagher,X J,C. Morrison, Dept, Ob/Gyn, Untv, Mississippi Med, Ctr., Jackson, MS Determine which method of induction is mosteneflcia1 for women at term with premature rupture of the membranes (ROM), Patient Population: Women (n = 96) 36-42 weeks' gestatlon wlth documented ROM « 6 hours, without labor or infection) were given informed consent and randomi zed to one of three groups, I ntervent ions: Expectant (E) pat tents were observed for labor, Oxytocin (0) induction was used in the second group whil e PGE2 gel (PG) was gi ven (4-mg dose every 6 hours) to patients in the third group, PG was repeated only in women who were not in active labor, Mai n Outcome Measures: Rupture to del i very interval, length of labor, maternal infectious complications, i nci dence of cesarean sect ton, hospital stay, and neonatal outcome parameters, Results: There were no Significant dtfferences in cervlCa'1exam on admission, length of labor, number of vaginal exams, infectious morbidity (maternal/neonatal), or Apgar scores between the three groups, Duration ROM (d) 1,45 ,76 ,89 Group E o PG N 31 25 35 Fetal Bradycardi a 4 o 1 Maternal Hospital Stay 3,6 + 1,4 2,6 + 0,7 2,5 + 1,0 The length of hospital stay was significantly longer in E versus 0 and PG (P = ,02) as was duration of ROM for E patients when compared to the other two groups (P ,01), There were no significant differences in the rate of cesarean birth and while neonatal morbidity was not different between the two groups, there was a significant increase in the number of patients with fetal bradycardia \ in E versus the other two groups (P = ,04), Conclusion: E management of ROM at or near term Significantly prolongs hospital stay without the beneftt of decreasing abdominal delivery rates and with an increased risk of fetal bradycardia,

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Volume 166 ~umbcr 1, Part 2

5 NEONATAL INTRAVENTRICULAR HEMORRHAGE (IVH) FOLLOWING MATERNAL BETA-SYMPATHOMIMETIC TOCOLYSIS,

LJ Groome, RL Goldenberg, SP Cl i ver,' RO Davi s, RL Copper,' University of Alabama Hospitals, Birmingham, Alabama

There has not been a reduction in neonatal morbidity or morta 1 ity associ ated with the wi despread use of B-mimet i c agents (BMA) to delay delivery, An increase in the incidence of IVH following B-mimetic tocolysis may be partly responsible for this lack of improvement even if delivery ;s delayed. This study was designed to determine if the incidence of IVH is increased in the offspri ng of women who recei ved a BMA for preterm 1 abor tocolysis. The population consisted of women who delivered singleton liveborn infants free of neurological anomalies at 25-36 weeks during a multicenter preterm birth prevention trial (1982-86). Based on factors such as gestational age and cervical dilatation, women in preterm labor were either not treated, given magnesium sulfate (MgSO.) or received a BMA. IVH was di agnosed by ultrasound, rout i ne 1 y performed on infants <1500 gms and as indicated at higher weights. Of the 1978 infants wi th ei ther spontaneous preterm 1 abor or PROM who del ivered preterm, 105 (5.3%) had IVH and 32 (1.6%) had grade III or IV IVH. Use of a BMA was associated with a 4-fold increase in the incidence of IVH compared to the use of either MgSO, or no toea 1 yt i c agent (p<O, 001). In vi rtua 11 y all preterm gestational age groups, there was a 2-fold and generally significant increase in the incidence of IVH following BMA tocolysis. A logistic regression analysis was performed

'adjusting for the type of tocolytic agent, gestational age at delivery, birthweight, medical center, route of delivery, indication for delivery, race, infant sex, and respiratory di st ress syndrome. The use of a BMA was found to be significantly associated with IVH [Ddds Ratio (OR) of 2,3 (1.23-4.29)]. In addition, BMA tocolysis was associated with a significant increase in the incidence of grades III and IV IVH when compared to no treatment [OR of 2,91 (I ,06-7,97)], This retrospective study suggests that BMA tocolytic therapy may be associated with at least a 2-fold increase in the incidence of IVH even when other ri sk factors are taken; nto account.

6 THE CANADI AN MULTI CENTRE ReT OF EARLY AMNI OTOMY,

WD FraserX, S Marcoux X, JM Moutqui D, A Chri steo X, BA Armson, JP Verreaul tX, N OkunX, C Ni mrod, AK Joshi x, H Cohen, L Bayer, T DoranX, P Bernstei 0, J Carfo) ) x, 5 Bottoms, F Gal Elroeau X, Laval Uni versi t y, Qu{'bec, Canada.

The goal of the study was to determine if a policy 01 earl y amni otomy for null i parae in tE'rm spontaneous labour is an effecti ve means to prevent dystoci a. In 11 centres, 925 W'Omen were randoml y aJ J ocatEld to either early amniotomy (ARM) or to conservation of the membranes (COM). For thE' purpose of thE' study, dystoci a was defi ned as a peri od of at I east 4 hours, after 3 cpnti meters di) atati on bad been achi ved, duri ng "'hi ch the mean rate of cervi cal di I atati on was -( 0.5 em/hr. Treatment groups were SI mi I ar wi th respect to age, GA, years of educati on, wei gbt, cervi cal status, and baby's bi rthwei ght. The medi an interval from faDdomi zati on to membrane rupture was 20 mi n. in t be ARM group and 230 mi n. in t he COM group. Epi dural anesthesi a and el ectroni c fetal moni tori ng were used wi th sl mi I ar frequency in the two groups. Oxytoci n was used pri or to a di agnosi s of dystoci a in a similar proportion of women in the two groups (ARM-

13.2%; COM - 11. 4%). Dystoci a was Jess frequent in the ARM group than in the COM group (33.6% VS 44.6%; p = 0.001). The mean interval from randomi zati on to del i very for women del i veri ng vagi nail y was approxi mate) y 1. 5 hours shorter j n t be ARM than j n the­cOMgroup (p -( 0.0001). The distribution of modes of del i ver y was si mi I ar j n the two groups. Groups were also comparable with respect to indicators of neonatal status (APGAR 5 -< 7, arterial cord pH -( 7.20, admi 55i on to I CU, cephal ohematoma). Thus, a pol i cy of earl y amni otomy was found to be protecti ve for dystocia by the study definition (RR = 0.75).

SPO Abstracts 275

7, EXPRESSION OF PARATHYROID HORMONE-RELATED PEPTIDE (PTHrP) mRNA IN PLACENTAL MEMBRANES AND AMNIOTIC FLUID (AF). Ferguson II JE, Gorman JX, Bruns DEx, Pandian MRx,+, Bruns MEHx, Departments of Obstetrics and Gynecology and Pathology, University of Virginia School of Medicine, Charlottesville, VA, and +Nichols Institute, San Juan Capistrano, CA

PTHrP was originally discovered in human tumors that produce hypercalcemia of malignancy, The hormone increases cyclic AMP and prostaglandin E2 in target tissues, but its physiological functions are unknown, We previously reported that PTHrP mRNA is expressed in laboring human uterus. We here report the unexpected finding that PTHrP is abundantly expressed in human amnion and reaches high concentrations in amniotic fluid, PTHrP mRNA was measured by computer-aided densitometry of Northern blot autoradiographs, The hormone was measured by use of a sandwich immunoassay. PTHrP mRNA abundance was 5-15 times that found in myometrium and exceeded that found even in lactating mouse mammary gland, the richest source previously identified, PTHrP mRNA abundance was decreased by 60% (p<0,025) in amnion from laboring (n=16) vs, non-laboring (n=16) women. The concentration of PTHrP in AF equaled or exceeded those found in serum of patients with hypercalcemia of malignancy, The mean concentrations of hormone in AF at 16 and 39 weeks were 21 ± 6 and 38 ± 11 pmol/L, respectively, These data suggest that the amnion sustains regulated abundant expression of PTHrP; the high concentrations of PTHrP in AF suggest an important role of PTHrP in normal pregnancy,

8 COMPARISON OF INDUCTION METHODS FOR PREMATURE RUPTURE OF MEMBRANES AT TERM. J,F, McCaul, L,M, Wi11iams,x R,W, Martin, E,F, Magann,X [, Gallagher,X J,C. Morrison, Dept, Ob/Gyn, Untv, Mississippi Med, Ctr., Jackson, MS

Ob~ective: Determine which method of induction is mosteneflcia1 for women at term with premature rupture of the membranes (ROM), Patient Population: Women (n = 96) 36-42 weeks' gestatlon wlth documented ROM « 6 hours, without labor or infection) were given informed consent and randomi zed to one of three groups, I ntervent ions: Expectant mana~ement (E) pat tents were observed for labor, Oxytocin (0) induction was used in the second group whil e PGE2 gel (PG) was gi ven (4-mg dose every 6 hours) to patients in the third group, PG was repeated only in women who were not in active labor, Mai n Outcome Measures: Rupture to del i very interval, length of labor, maternal infectious complications, i nci dence of cesarean sect ton, hospital stay, and neonatal outcome parameters, Results: There were no Significant dtfferences in cervlCa'1exam on admission, length of labor, number of vaginal exams, infectious morbidity (maternal/neonatal), or Apgar scores between the three groups,

Duration ROM (d)

1,45 ,76 ,89

Group E o PG

N 31 25 35

Fetal Bradycardi a

4 o 1

Maternal Hospital Stay

3,6 + 1,4 2,6 + 0,7 2,5 + 1,0

The length of hospital stay was significantly longer in E versus 0 and PG (P = ,02) as was duration of ROM for E patients when compared to the other two groups (P • ,01), There were no significant differences in the rate of cesarean birth and while neonatal morbidity was not different between the two groups, there was a significant increase in the number of patients with fetal bradycardia \ in E versus the other two groups (P = ,04), Conclusion: E management of ROM at or near term Significantly prolongs hospital stay without the beneftt of decreasing abdominal delivery rates and with an increased risk of fetal bradycardia,