37 Amniotic Fluid Infection (AFI) and Preterm Labor in Rhesus Macaques

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SPO Abstracts

IS BACTERIAl ENDOTOXIN A CAUSE OF MECONIUM PASSAGE IN UTERO? R. Romero, M. Mazor, W. Sepulveda,x F. Brandt,X R. Gonzalez,x M. Ramirez,x E. Behnke,x Depts. of Ob/Gyn, Yale Univ. Sch. of Med., New Haven, CT; Wayne State Univ., Detroit, MI; Soroka Med. Center, Ben Gurion Univ., Israel; Sotero del Rio Hosp., Santiago, Chile The causes of meconium passage during labor are largely unknown. Although hypoxia and acidosis are frequently considered as causes of meconium-stained amniotic fluid (MS-AF), fetal pH and blood gases are within normal range in most cases. Intraamniotic infection has been recently implicated as a cause of MS-AF in preterm labor (NOG 1991;164:859). No

January 1992 Am J Obstet Gynecol

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x

x

S Baggia , SS Wi tkin , MJ Navy.

x

Depts Ob/Gyn OHSU and

Cornell, and Oregon Reg Primate Res Ctr, Portland, OR. To study the relationship between AFI, cytokines, prostaglandins (PG), and preterm labor. ex perimenta AFI was established by intra-amniotic inoculation of 10 cfu Group B streptococci in 4 chronically instrumented Rhesus monkeys at 130 days gestation (term is 167 days). Amniotic

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fluid (AF) was sampled sequentially for bacteria, TNF-CI (bioassay), IL-IB (ELISA), and PG (specific RIA).

Uterine

contractility was recorded as the hourly area under the contraction curve and expressed as HCA in mmHg. sec/hr. Increases in the HCA occurred at 28 hrs (14-36) after inoculation in all 4 monkeys and led to progressive cervical dilatation in 3 of 4. These contractions were of highamplitude. low-frequency. and long-duration. AF TNF rose

A case-rontrol study was designed to compare the detection rate of bacterial endotoxin in clear (n = 88) and MS-AF (n = 88). Endotoxin was assayed with the gel clol limulus amebocyte lysate assay (LAL) using a method previously described (sensitivity = 100 pg/ml) (NOG 1987;157:815). Results: 1) The rate of positive LAl was greater in MS-AF than in clear AF (44.3% [39/88] vs. 4.5% [4/88]; p <0.(01). 2) After heat treatment at 100°C for 4 minutes (a method to inactivate non-endotoxin-cross-reacting substances), 43.5% (17/39) of MS-AF

from 48 pg/ml before inoc. to 20,000 pg/ml 9 hrs (6-14)

after inoc. and 20 hrs (8-34) before increases in the HCA. Parallel increases in IL-1B (from 10 pg/mI to 1,142 pg/ml) ,

PGE • and PGF occurred 18 hrs (12-24) after inoc. and 10 ~rs (2-18)2g rior to increases in the HCA. In contrast, spontaneous term labor in 4 control monkeys was not associated with increases in AF TNF or IL-1B and contractions were of high-ampli tude, high-frequency. and short-duration.

had a repeat positive tAL assay, while only one of four clear AF remained

positive. 3) Endotoxin was present more commonly in MS-AF than in clear AF (19.3% [17/88] vs. 3.4% [3/88]; p <0.(01). 4) Microorganisms were identified by Gram stain in 12.7% (11/86) of MS-AF and in only 3.5% (3/64) of clear AF (p < 0.05). Conclusions: 1) Bacterial endotoxin is frequenlly present in patients with MS-AF. 2) MS-AF contains a heat-labile substance that cross-reacts with

We conclude:

I) AFI wi th GBS leads to a predictable in-

crease in uterine contractility which is different than spontaneous labor; and 2) in AFI, increases in AF cytokines and PG occur prior to increases in uterine contractility.

endotoxin in the LAl assay. 3) Intraamniotic infection may be an important and previously unrecognized cause of MS-AF. These findings are novel and have important clinical implications for intrapartum and neonatal management.

PLACENTA NATURAL KILLER CELL CYTOTOXICITY (NKC) IN HUMAN IMMUNODEF1CIENCY VIRUS (HIV) INFECfED PARTURIENfS. B. Gonik, L. Loo,x J. Reuben,x T. Cowles, A. Helfgott, A. Harris; M. Doyle; Depts. Ob/Gyn/Repro Sci, Peds., and Irnmunol. Univ. of Texas Med. School and MD Anderson Cancer Ctr., Houston, TX HIV disease is characterized by host immune dysfunction and opportunistic infection. Infants born of HIV-infected mothers are at-risk for transplacental acquisition of HIV infection, along with the passage of other potential pathogens into the fetal compartment. To better assess the functional capabilities of the placenta as an immune barrier, we examined placental NKC in 7 HIV-infected and 7 control parturients. Following removal of the maternal decidua, cotyledon-derived tissues were minced and the cells dispersed with Dispase. A FicoU-paque gradient was used to isolate placental mononuclear cells. In a subset of experiments using a DNA hybridization probe for the Y chromosome, the separated cells were determined to be > 75% fetal in origin. NKC was measured using a 4 hour chromium-release assay with labelled K562 target cells at an effector to target cell ratio of 100:1. Clinically, the majority of the HIV-infected subjects were classified as group II by CDC criteria, delivered at or near term (37.6 ± 2.8 weeks), and had infants who weighed significantly less (p
x

x

information is available regarding the relationship between the presence of microorganisms and/or their products in AF and meconium passage during term labor. Bacterial endotoxin, a component of the cell wall of Gram-negative bacteria, is a potent bioactive agent that can stimulate gastrointestinal peristalsis and lead to meconium passage in utero. Materials and Methods:

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AMNIOTIC FLUIO INFECTION CAFl) AN> PRETERM LABOO IN RHESUS MACAQUES_ MG Gravett, GJ Haluska, JL Edwards, MJ Cook

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DOES THE RISK OF PERINATAL TRANSMISSION OF HIV-I INCREASE WITH SUBSEQUENT PREGNANCIES? RR Viscarello, DeGennaro>, YG Gollin>, WA Andiman>, JC Hobbins, Yale University School of Medicine, New Haven, CT.

m

Early reports of the rate of vertical transmission of HIV -I in mothers who had delivered an index child with AIDS or ARC were as high as 65 80%. Recent, prospective studies have estimated the rate to be 7 to 33%. No study to date has examined the transmission rate in successive pregnancies. We studied 62 infants born to 27 HIV -positive women to determine if the risk of perinatal transmission of HIV-1 increases with subsequent pregnancies. There were 23 Blacks, three Hispanics, and one Caucasian. Eighteen of the women were current or previous IVDAs and 9 were infected heterosexually. Nineteen women had two pregnancies while infected and 8 had three. There are 14 infants currently COC Stage PO who were excluded from the analysis. The remaining 48 infants were classified according to CDC criteria into three groups: Seroreverted, PI, and P2, and stratified according to birth order. No statistically significant difference was found between infant disease status and birth order using Chi-square analysis. Mean gestational age at time of delivery and mean birth weight were inversely-related to birth order as follows: Pregnancy # 1: 37.3 wks ± 3 and 28l4g ± 532; Pregnancy # 2: 36.6 wks ± 3 and 2768g ± 427; Pregnancy # 3: 35.3 wks ± 2 and 2226g ± 795. Maternal factors, including low CD4 cell count, positive HIV p24 antigen status, and maternal COC Group IV disease (AIDS), were positively correlated with the presence of disease in the infan~ but not with birth order. Our data does not support an increased risk of vertical transmission of HIV-1 with successive pregnancies. Markers of maternal viremia or immunodeficiency may be more accurate predictors of transmission of HIV-1. (This research was partially supported by a grant from the American Foundation for AIDS Research and the Pediatric AIDS Foundation AmFAR/pAF #50034-7). to