Opioid effect on the autonomic nervous system in a fetal sheep model.

PURPOSE: Opioid use during labour can interfere with cardiotocography patterns. Heart rate variability indirectly reflects a fluctuation in the autonomic nervous system and can be monitored through time and spectral analyses. This experimental study aimed to evaluate the impact of nalbuphine administration on the gasometric, cardiovascular, and autonomic nervous system responses in fetal sheep. METHODS: This was an experimental study on chronically instrumented sheep fetuses (surgery at 128 ± 2 days of gestational age, term = 145 days). The model was based on a maternal intravenous bolus injection of nalbuphine, a semisynthetic opioid used as an analgesic during delivery. Fetal gasometric parameters (pH, pO2, pCO2, and lactates), hemodynamic parameters (fetal heart rate and mean arterial pressure), and autonomic nervous system tone (short-term and long-term variation, low-frequency domain, high-frequency domain, and fetal stress index) were recorded. Data obtained at 30-60 min after nalbuphine injection were compared to those recorded at baseline. RESULTS: Eleven experiments were performed. Fetal heart rate, mean arterial pressure, and activities at low and high frequencies were stable after injection. Short-term variation decreased at T30 min (P = 0.02), and long-term variation decreased at T60 min (P = 0.02). Fetal stress index gradually increased and reached significance at T60 min (P = 0.02). Fetal gasometric parameters and lactate levels remained stable. CONCLUSION: Maternal nalbuphine use during labour may lead to fetal heart changes that are caused by the effect of opioid on the autonomic nervous system; these fluctuations do not reflect acidosis.

Maternal buprenorphine treatment and fetal neurobehavioral development.

BACKGROUND: Gestational opioid use/misuse is escalating in the United States; however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders. OBJECTIVE: The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development. STUDY DESIGN: Forty-nine buprenorphine-maintained women who attended a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (ie, heart rate, motor activity, and their integration [fetal movement-fetal heart rate coupling]) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchic linear modeling. RESULTS: Fetal heart rate, heart rate variability, and heart rate accelerations were significantly reduced at peak vs trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks gestation and tended to intensify with advancing gestation. Fetal motor activity and fetal movement-fetal heart rate coupling were depressed from peak to trough at 36 weeks gestation. Polysubstance exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks gestation. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough. CONCLUSION: Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (≥13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects, relatively good outcomes of buprenorphine-exposed infants, and recognition of the benefits of medication-assisted treatment for pregnant women with opioid use disorders in optimizing pregnancy outcomes.

Intraoperative Treatment of Fetal Asystole After Endovascular Repair of Aortic Coarctation in a Pregnant Woman with Mitral Stenosis.

A G1P0 woman with aortic coarctation and mitral valve stenosis underwent endovascular aortic repair with continuous fetal monitoring during the 20th week of pregnancy. On tracheal extubation, an episode of fetal asystole followed by fetal bradycardia was identified. Ephedrine, nitroglycerin, and terbutaline were administered for intrauterine fetal resuscitation. Subsequently, the patient developed hypertension and pulmonary edema, which were treated with furosemide and noninvasive positive pressure ventilation. The fetal heart rate normalized. We conclude that intraoperative monitoring of a previable fetus may aid in optimizing maternal hemodynamics. Before performing interventional procedures in pregnant women, a multidisciplinary team should discuss the goals of neonatal care should adverse fetal events be detected.

Anesthetic techniques for fetal surgery: effects of maternal anesthesia on intraoperative fetal outcomes in a sheep model.

BACKGROUND: Use of high-dose inhalational anesthesia during open fetal surgery may induce maternal-fetal hemodynamic instability and fetal myocardial depression. The authors' preliminary human retrospective study demonstrated less fetal bradycardia and left ventricular systolic dysfunction with lower dose desflurane supplemented with propofol and remifentanil IV anesthesia (SIVA). In this animal study, the authors compare maternal-fetal effects of high-dose desflurane anesthesia (HD-DES) and SIVA. METHODS: Of 26 instrumented midgestational ewes, data from 11 animals exposed to both SIVA and HD-DES in random sequences and six animals exposed to HD-DES while maternal normotension was maintained were analyzed. Maternal electroencephalography was used to guide comparable depths of anesthesia in both techniques. Hemodynamic parameters, blood gas, and fetal cardiac function from echocardiography were recorded. RESULTS: Compared with SIVA, HD-DES resulted in significant maternal hypotension (mean arterial pressure difference, 19.53 mmHg; 95% CI, 17.6-21.4; P < 0.0001), fetal acidosis (pH 7.11 vs. 7.24 at 150 min, P < 0.001), and decreased uterine blood flow. In the HD-DES group with maternal normotension, uterine blood flow still declined and fetal acidosis persisted, with no statistically significant difference from the group exposed to HD-DES that had maternal hypotension. There was no statistically significant difference in fetal cardiac function. CONCLUSION: In sheep, SIVA affects maternal hemodynamics less and provides better fetal acid/base status than high-dose desflurane. Fetal echocardiography did not reflect myocardial dysfunction in this model.

The effect of abused substances on antenatal and intrapartum fetal testing and well-being.

Recognition that use and abuse of substances by pregnant patients perpetuates, despite ongoing efforts to educate the public, necessitates clinicians to integrate understanding of potential effects on antepartum and intrapartum fetal testing into their interpretation and implementation of clinical findings. This includes acknowledging some anticipated alterations in results and selecting the appropriate type and frequency of testing methods and interventions. Certain substances are well documented in terms of expected variations in test results; others are not as clearly defined. An overview of information that may be helpful to the clinician is presented to promote understanding of fetal evaluation performed through common tests such as contraction stress test, the nonstress test, the biophysical profile, the modified biophysical profile, fetal movement counting, and Doppler velocimetry. What evidence is available should be used to assist in defining the actual status of the fetus as best as possible, even when the effects of substances may be unknown or have obscure results.

Glucocorticoid treatment does not alter early cardiac adaptations to growth restriction in preterm sheep fetuses.

OBJECTIVE: To study the consequences of glucocorticoid treatment in fetal growth restriction (FGR) on cardiac function. SETTING: Laboratory. SAMPLE: Sheep. METHODS: Growth restriction was induced in sheep fetuses using single umbilical artery ligation (SUAL) on days 105-110 of gestation (term 147). Control fetuses were not ligated. Betamethasone (BM) (11.4 mg intramuscularly) or saline was administered to ewes on days 5 and 6 after surgery. Ewes were anaesthetised on day 7, the fetuses were removed, and their hearts were mounted on a Langendorff apparatus. Balloon catheters were inserted into the right and left ventricles. OUTCOME MEASURES: Ventricular contractile function and infarct area following ischaemia/reperfusion. RESULTS: The SUAL resulted in FGR (body weight 77% of control). The FGR was associated with increases in basal left ventricular pressure development and rates of contraction and relaxation. Right ventricular contraction was unaffected. Following brief ischaemia/reperfusion, the infarct area in FGR hearts was increased four-fold compared with controls. Antenatal BM resulted in a proportional increase in heart size and coronary flow, especially in FGR fetuses, and left ventricular pressure and heart rate responses to ß-adrenoceptor activation were increased. CONCLUSIONS: Fetal hearts rapidly adapt to FGR to maintain substrate delivery to the brain and heart. The FGR greatly enhanced the area of ischaemia, with implications for susceptibility in postnatal life. Antenatal BM treatment does not interfere with these cardiac changes but appears to increase left ventricle ß-adrenoceptor responsiveness, which may render the offspring vulnerable to subsequent cardiac dysfunction.

Maternal hypoxia and caffeine exposure depress fetal cardiovascular function during primary organogenesis.

AIMS: Hypoxia is known to influence cardiovascular (CV) function, in part, through adenosine receptor activation. We have shown in a mouse model that during primary cardiac morphogenesis, acute maternal hypoxia negatively affects fetal heart rate, and recurrent maternal caffeine exposure reduces fetal cardiac output (CO) and downregulates fetal adenosine A(2A) receptor gene expression. In the present study, we investigated whether maternal caffeine dosing exacerbates the fetal CV response to acute maternal hypoxia during the primary morphogenesis period. MATERIAL AND METHODS: Gestational-day-11.5 pregnant mice were exposed to hypoxia (45 s duration followed by 10 min of recovery and repeated 3 times) while simultaneously monitoring maternal and fetal CO using high-resolution echocardiography. RESULTS: Following maternal hypoxia exposure, maternal CO transiently decreased and then returned to pre-hypoxia baseline values. In contrast to a uniform maternal cardiac response to each exposure to hypoxia, the fetal CO recovery time to the baseline decreased, and CO rebounded above baseline following the second and third episodes of maternal hypoxia. Maternal caffeine treatment inhibited the fetal CO recovery to maternal hypoxia by lengthening the time to CO recovery and eliminating the CO rebound post-recovery. Selective treatment with an adenosine A(2A) receptor antagonist, but not an adenosine A(1) receptor antagonist, reproduced the altered fetal CO response to maternal hypoxia created by caffeine exposure. CONCLUSIONS: Results suggest an additive negative effect of maternal caffeine on the fetal CV response to acute maternal hypoxia, potentially mediated via adenosine A(2A) receptor inhibition during primary cardiovascular morphogenesis.

A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep.

Virtually nothing is known about the effects on fetal physiology of xanthine oxidase inhibition. This is despite maternal treatment with the xanthine oxidase inhibitor allopurinol being considered in human complicated pregnancy to protect the infant's brain from excessive generation of ROS.We investigated the in vivo effects of maternal treatment with allopurinol on fetal cardiovascular function in ovine pregnancy in late gestation. Under anaesthesia, pregnant ewes and their singleton fetus were instrumented with vascular catheters and flow probes around an umbilical and a fetal femoral artery at 118±1 dGA (days of gestational age; termca. 145 days). Five days later, mothers were infused I.V. with either vehicle (n =11) or allopurinol (n =10). Fetal cardiovascular function was stimulated with increasing bolus doses of phenylephrine (PE) following maternal vehicle or allopurinol. The effects of maternal allopurinol on maternal and fetal cardiovascular function were also investigated following fetal NO blockade (n =6) or fetal ß1-adrenergic antagonism (n =7). Maternal allopurinol led to significant increases in fetal heart rate, umbilical blood flow and umbilical vascular conductance, effects abolished by fetal ß1-adrenergic antagonism but not by fetal NO blockade. Maternal allopurinol impaired fetal α1-adrenergic pressor and femoral vasopressor responses and enhanced the gain of the fetal cardiac baroreflex. These effects of maternal allopurinol were restored to control levels during fetal NO blockade. Maternal treatment with allopurinol induced maternal hypotension, tachycardia and acid­base disturbance. We conclude that maternal treatment with allopurinol alters in vivo maternal, umbilical and fetal vascular function via mechanisms involving NO and ß1-adrenergic stimulation. The evidence suggests that the use of allopurinol in clinical practice should be approached with caution.

A performance improvement process to tackle tachysystole.

Inappropriate use of oxytocin is an important patient safety issue. In this article, the authors describe success in "tackling tachysystole" using an evidence-based algorithm for oxytocin administration. Monthly audits (N = 1160) reached 100% compliance. An algorithm posted at the bedside, multidisciplinary follow-up, education, and widely disseminated results helped counter resistance and normalization of deviance. Clinicians need standardized definitions and guidelines with measures of progress to manage safety concerns such as tachysystole.

First-trimester fetal heart rate in mothers with opioid addiction.

AIM: To investigate the difference in fetal heart rate of opioid-dependent mothers compared to non-dependent mothers in the first trimester of pregnancy. DESIGN: The data of 74 consecutive singleton pregnancies of mothers enrolled in a maintenance programme for opioid-dependent women was matched to 74 non-exposed singleton pregnancies by maternal age, crown-rump length, smoking status, ethnic background and mode of conception. MEASUREMENT: Fetal heart rate measured as part of first-trimester screening by Doppler ultrasound between 11+0 and 13+6 gestational weeks was compared retrospectively. FINDINGS: The mean fetal heart rate in opioid-dependent mothers was 156.0 beats per minute (standard deviation 7.3) compared to 159.6 (6.5) in controls. The difference in fetal heart rate was significant (P = 0.02). There was a significant difference in mean maternal body mass index (P = 0.01) but not in mean nuchal translucency (P = 0.3), gestational age (0.5), fetal gender (P = 0.3) and parity (P = 0.3) between both groups. Fifty-five per cent (41 of 74) of cases were taking methadone, 30% (22 of 74) buprenorphine and 15% (11 of 74) were taking slow-release morphines throughout the pregnancy. CONCLUSIONS: In fetuses of opioid-dependent mothers a decreased fetal heart rate can already be observed between 11+0 and 13+6 gestational weeks. The effect of opioid intake needs to be taken into consideration when interpreting fetal heart rate in opioid-dependent mothers at first-trimester screening.

A case study of a pregnant patient with a congenital heart block accompanied by left isomerism and uncontrolled type 2 diabetes who was treated successfully with ritodrine.

We present a case study of a patient with a congenital heart block associated with a left isomerism that was diagnosed during the 26th week of gestation. The mother had type 2 diabetes mellitus that was difficult to control during the early stages of the pregnancy. A fetal echocardiogram revealed an atrioventricular dissociation, with an atrial rate of 120 bpm and a ventricular rate of 55 bpm. Subsequent examinations also revealed a left isomerism in the fetus. To increase the fetal heart rate, a continuous intravenous infusion of ritodrine was administered. The fetal ventricular rate rapidly increased to 65 bpm. The pregnancy successfully continued until term and a female infant weighing 3,182 g was born via a cesarean section. A subsequent surgery was performed to provide the infant with a permanent cardiac pacemaker, and notably, the child is now 4 months of age and her growth has been within the normal range.

Fetal and offspring arrhythmia following exposure to nicotine during pregnancy.

Although recent studies have demonstrated prenatal nicotine can increase cardiovascular risk in the offspring, it is unknown whether exposure to nicotine during pregnancy also may be a risk for development of arrhythmia in the offspring. In addition, in previous studies of fetal arrhythmia affected by smoking, only two patterns, bradycardia and tachycardia, were observed. The present study examined acute effects of maternal nicotine on the fetal arrhythmia in utero, and chronic influence on offspring arrhythmia at adult stage following prenatal exposure to nicotine. Nicotine was administered to pregnant ewes and rats. In the fetal sheep, intravenous nicotine not only induced changes of fetal heart rate, but also caused cardiac cycle irregularity, single and multiple dropped cardiac cycles. Although maternal nicotine had no influence on fetal blood pH, lactic acid, hemocrit, Na(+), K(+) levels and plasma osmolality, fetal blood PO(2) levels were significantly decreased following maternal nicotine in ewes. In offspring rats at 4-5 months after birth, prenatal exposure to nicotine significantly increased heart rate and premature ventricular contraction in restraint stress. In addition, arrhythmias induced by injection of nicotine were higher in the offspring prenatal exposure to nicotine in utero. The results provide new evidence that exposure to nicotine in pregnancy can cause fetal arrhythmia in various patterns besides tachycardia and bradycardia, the possible mechanisms for nicotine-induced fetal arrhythmia included in utero hypoxia. Importantly, following exposure to nicotine significantly increased risk of arrhythmia in the adult offspring. The finding offers new insight for development of cardiac rhythm problems in fetal origins.

Monitorização materno-fetal durante procedimento odontológico em portadora de cardiopatia valvar / Maternal-fetal monitoring during dental procedure in patients with heart valve disease / Monitoreo maternofetal durante procedimiento odontológico en portadora de cardiopatía valvular

FUNDAMENTO: Os efeitos da anestesia local em odontologia com lidocaína e epinefrina, sobre parâmetros cardiovasculares de gestantes portadoras de valvopatias e seus conceptos, não estão esclarecidos. OBJETIVO: Avaliar e analisar parâmetros da cardiotocografia, de pressão arterial e eletrocardiográficos da gestante portadora de doença valvar reumática, quando submetida à anestesia local com 1,8 ml de lidocaína 2 por cento sem vasoconstritor e com epinefrina 1:100.000, durante procedimento odontológico restaurador. MÉTODOS: Realizamos monitorização ambulatorial da pressão arterial, eletrocardiografia ambulatorial materna e cardiotocografia de 31 portadoras de cardiopatia reumática, entre a 28ª e 37ª semana de gestação, divididas em dois grupos conforme presença ou não do vasoconstritor RESULTADOS: Demonstrou-se redução significativa dos valores de frequência cardíaca materna nos dois grupos, durante o procedimento, quando comparado aos demais períodos (p < 0,001). Houve ocorrência de arritmia cardíaca em 9 (29,0 por cento) pacientes, das quais 7 (41,8 por cento) pertencentes ao grupo de 17 gestantes que recebeu anestesia com adrenalina. A pressão arterial materna não apresentou diferença quando comparamos períodos ou grupos (p > 0,05). O mesmo ocorreu (p > 0,05) com número de contrações uterinas, nível e variabilidade da linha de base e número de acelerações da frequência cardíaca fetal. CONCLUSÃO: O uso de 1,8 ml de lidocaína 2 por cento associado à adrenalina mostrou-se seguro e eficaz em procedimento odontológico restaurador durante a gestação de mulheres com cardiopatia valvar reumática.

BACKGROUND: The effects of local dental anesthesia with lidocaine and epinephrine on cardiovascular parameters of pregnant women with heart valve diseases and their fetuses are not fully understood. OBJECTIVES: To assess and analyze cardiotocographic, blood pressure and electrocardiographic parameters of pregnant women with rheumatic heart valve disease undergoing local anesthesia with 1.8mL of lidocaine 2 percent with or without epinephrine 1:100,000 during restorative dental treatment. METHODS: Maternal ambulatory blood pressure and electrocardiographic monitoring as well as cardiotocography of 31 patients with rheumatic heart disease were performed between the 28th and 37th week of gestation. The patients were divided into two groups, those with or without vasoconstrictor. RESULTS: A significant reduction in maternal heart rate was shown in both groups during the procedure in comparison with the other periods (p<0.001). Cardiac arrhythmia was observed in nine (29.0 percent) patients, of which seven (41.8 percent) were from the group of 17 pregnant women who received anesthesia plus epinephrine. No difference in maternal blood pressure was observed when periods or groups were compared (p>0.05). The same occurred (p>0.05) with the number of uterine contractions, baseline level and variability, and number of accelerations of fetal heart rate. CONCLUSION: The use of 1.8mL of lidocaine 2 percent in combination with epinephrine was safe and efficient in restorative dental procedures during pregnancy in women with rheumatic heart valve disease.

FUNDAMENTO: Los efectos de la anestesia local en odontología con lidocaína y epinefrina, sobre los parámetros cardiovasculares de gestantes portadoras de valvulopatías y sus conceptos, no son claros. OBJETIVO: Evaluar y analizar parámetros de la cardiotocografía, de la presión arterial y electrocardiográficos de la gestante portadora de enfermedad valvular reumática, al someterse a anestesia local con 1,8 ml de lidocaína 2 por ciento sin vasoconstrictor y con epinefrina 1:100.000, durante procedimiento odontológico restaurador. MÉTODOS: Realizamos monitoreo ambulatorio de la presión arterial, electrocardiografía ambulatoria materna y cardiotocografía de 31 portadoras de cardiopatía reumática, entre la 28ª y la 37ª semana de gestación, divididas en dos grupos según la presencia o no del vasoconstrictor. RESULTADOS: Se observó reducción significativa de los valores de frecuencia cardíaca materna en los dos grupos, durante el procedimiento, al compararlo con los demás períodos (p < 0,001). Se registró ocurrencia de arritmia cardíaca en 9 (29,0 por ciento) pacientes, de las cuales 7 (41,8 por ciento) pertenecían al grupo de 17 gestantes que recibió anestesia con adrenalina. La presión arterial materna no presentó diferencia al comparar períodos o grupos (p > 0,05). Lo mismo ocurrió (p > 0,05) con el número de contracciones uterinas, nivel de variabilidad de la línea de base y número de aceleraciones de la frecuencia cardíaca fetal. CONCLUSIÓN: El uso de 1,8 ml de lidocaína 2 por ciento asociado a la adrenalina se mostró seguro y eficaz en procedimiento odontológico restaurador durante la gestación de mujeres con cardiopatía valvular reumática.

Low doses of nicotine-induced fetal cardiovascular responses, hypoxia, and brain cellular activation in ovine fetuses.

Prenatal exposure to nicotine is associated with a variety of adverse outcomes. The present study investigated the effect of low doses of nicotine during pregnancy on fetal blood gases, cardiovascular system, and cellular activation in the brain. Intravenous administration of nicotine 10 or 25 microg/kg into ewe did not affect maternal blood gases, blood pressure, and heart rate. Maternal administration of nicotine also had no effect on fetal blood electrolyte concentrations, osmolality levels, and lactic acid levels. However, it significantly reduced fetal blood pO2 levels and oxygen saturation, increased fetal arterial blood pressure and decreased heart rate in utero. In addition, exposure to low doses of nicotine increased the expression of Fos in the paraventricular nucleus (PVN) and subfornic organ (SFO) in the fetal brain. The data demonstrated that even low doses of nicotine could impact significantly on fetal cardiovascular and central nervous systems, as well as oxygen status, and suggested a toxic risk to fetuses of exposure to low levels nicotine or second-hand smoking during pregnancy.

Persistent changes in arterial blood gases in fetal sheep.

Two anaesthetic protocols were compared using pregnant sheep. In both groups of animals, anaesthesia was induced using an intravenous (i.v.) injection of diazepam and ketamine. The ewes were then intubated for positive pressure ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8% halothane. If the ewe showed any signs of awakening, one of two protocols was followed. First, the halothane concentration was increased to 2-3% until the ewe was completely anaesthetized. Second, the halothane concentration was not altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1 mg/kg) until again completely anaesthetized. At the completion of surgery, maternal recovery was rapid and similar between the two groups. However, five days after surgery, the fetal arterial Po(2) and oxygen content of the fetuses receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were statistically significantly depressed when compared with the fetuses receiving additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL). These results led us to conclude that certain anaesthetic protocols, in spite of good maternal recovery, can lead to deleterious effects upon the fetus that persist for at least five days after surgery.

Proliferative responses in the placenta after endotoxin exposure in preterm fetal sheep.

OBJECTIVES: Antenatal infections are associated with an increased risk of perinatal morbidity and mortality. Systemic application of endotoxins to the fetus results in an increase in placental vascular resistance and chronic reduction in umbilical blood flow. We studied morphological alterations of the placenta in response to fetal inflammation in the preterm sheep. STUDY DESIGN: Therefore, 14 fetal sheep were chronically instrumented at a mean gestational age of 107+/-1 days (term is 147 days). Four days after surgery fetuses received 100 ng lipopolysaccharide (LPS; n=8) or saline (control; n=6) intravenously. Fetal heart rate and arterial blood pressure were monitored continuously while blood gases and acid-base balance were measured at time points 0, +1, +3, +6, +12, +24, +48 and +72 h. Three days after LPS application placental cotyledons were analyzed by immunohistochemistry and morphometry. Different primary antibodies like AE 1 and AE 3 against cytokeratins were used. Secondary antibodies were visualized with 3-amino-9-ethylcarbazole (AEC) or using the Vectastain kit (Vector Laboratories, Burlingame, CA). Double staining was carried out first by utilizing Vectastain kit (black), followed by AEC staining (red). Counterstaining was performed with haematoxylin. RESULTS: Fetal tachycardia and hypertension were induced transiently during the first 12h after LPS application. Fetuses suffered from mild hypoxaemia while acidemia was absent. Morphometry revealed a non-significant shift in the relation of maternal and fetal placental compartments towards the maternal parts in response to LPS treatment. Endotoxin induced an increased proliferation in both compartments of the placenta with a 3.2-fold increase on the maternal and a 1.8-fold increase on the fetal side. CONCLUSIONS: Systemic endotoxin exposure of the preterm fetal sheep leads to a change in the gross organization of the placenta and changes in the proliferation patterns in both placental compartments. These rearrangements inside the placenta may disturb its organ function and subsequently lead to fetal morbidity associated with the fetal inflammatory response syndrome and chronic placental dysfunction, respectively.