F prostaglandin levels in amniotic fluid in premature labour

The concentration of prostaglandin F (PGF) in amniotic fluid was measured by radioimmunoassay in 27 patients admitted in premature labour. There was a strong correlation between PGF levels in amniotic fluid and both cervical dilatation (r = 0.81; P < 0.001) and duration of labour (r = 0.79; P < 0.001). Cervical dilatation greater than 7 cm was associated with levels exceeding 2000 pg/ml. When contractions were present for less than one hour, levels of PGF were below 50 pg/ml. Low levels of PGF were found in amniotic fluid from a separate group of three patients, of whom two had cervical incompetence. It is concluded that the onset of premature labour is not associated with elevated levels of PGF in amniotic fluid. During premature labour, concentrations rise to an extent comparable to that observed in labour at term.     

A method for continuous monitoring of meconium in the amniotic fluid during labour

In about 10% of pregnancies overall, the fetus discharges meconium (its bowel contents) into the amniotic fluid during labour. In about 10% of cases where meconium is passed, the fetus gasps, inhaling the sticky meconium into the upper respiratory tract. After birth, the meconium blocks the air passages in the lungs, impairing gas exchange — meconium aspiration syndrome (MAS). Up to 20% of infants suffering from MAS die and recently published studies have shown a long-term effect of MAS in causing cough and wheeze. The risk of meconium aspiration is thought to be increased by intrauterine hypoxia. At present, meconium is only noticed at birth or occasionally when amniotic fluid leaks past the presenting part of the fetus. A method has been developed which measures absolute meconium concentration with a 99% prediction interval of ± 30 gl⁻¹; allows monitoring of the rate of appearance of meconium linearly with a nonlinearity of 5%, and differentiates between meconium and blood. The method uses the ratio of the intensity of back-scattered light from the amniotic fluid at 700 and 415 nm, the latter being near the peak of light absorption by meconium and the former a reference value. The ratio is also affected by the presence of blood. However, blood has specific absorption peaks at 540 and 575 nm from which it can be detected (the presence of blood is also a significant abnormality, and is relatively uncommon). The measurement method could easily be integrated into an optical sensor mounted onto an intrauterine probe. The measurement of back-scattered light at 415, 540 and 700 nm would allow continuous monitoring of meconium which could provide valuable information for the study of the pathophysiology of meconium passage in utero during labour and allow preventative measures to be developed.     

Preinduction cervical priming in high risk pregnancy — experience with a new sustained release PGE2 vaginal film

Experience with a new sustained release PGE2 formulation is presented. 111 high risk primiparae with very poor cervical scores (<3) were studied. In 59 patients, labour was induced by forewater amniotomy and I.V. oxytocin. In the remaining 52 patients, film containing 850 ug of PGE₂ was inserted into the vagina to ripen the cervix 24 hours prior to induction of labour. Indications for elective delivery and maternal characteristics were similar in both groups. There were significant changes in the cervical state within 12 hours of vaginal insertion. By 24 hours, 19 patients receiving vaginal film (36.5%) had established labour of whom 13 proceeded to vaginal delivery. Significantly fewer patients in the priming group required Caesarean delivery. No untoward maternal or fetal side effects were observed.Safety, ease of administration and efficacy make this new PGE₂ formulation a useful agent for priming of the very poor primiparous cervix prior to induction of high risk labour.     

Is Vitamin D Binding Protein a Novel Predictor of Labour?

Vitamin D binding protein (VDBP) has previously been identified in the amniotic fluid and cervicovaginal fluid (CVF) of pregnant women. The biological functions of VDBP include acting as a carrier protein for vitamin D metabolites, the clearance of actin that is released during tissue injury and the augmentation of the pro-inflammatory response. This longitudinal observational study was conducted on 221 healthy pregnant women who spontaneously laboured and delivered either at term or preterm. Serial CVF samples were collected and VDBP was measured by ELISA. Binary logistic regression analysis was performed to assess the utility of VDBP as a predictor of labour. VDBP in the CVF did not change between 20 and 35 weeks'' gestation. VDBP measured in-labour was significantly increased 4.2 to 7.4-fold compared to 4–7, 8–14 and 15–28 days before labour (P<0.05). VDBP concentration was 4.3-fold significantly higher at 0–3 days compared to 15–28 days pre-labour (P<0.05). The efficacy of VDBP to predict spontaneous labour onset within 3 days provided a positive and negative predictive value of 82.8% and 95.3% respectively (area under receiver operator characteristic curve  = 0.974). This longitudinal study of pregnant women suggests that VDBP in the CVF may be a useful predictor of labour.     

Staphylococcus lugdunensis Cultured from the Amniotic Fluid at Caesarean Section

Staphylococcus lugdunensis is a virulent coagulase-negative staphylococcus. It behaves like and can be mistaken in culture for Staphylococcus aureus. While originally thought to be a skin commensal rarely responsible for opportunistic infection, it was rapidly established as a significant human pathogen. It has been mainly associated with native and prosthetic valve endocarditis, osteomyelitis, and skin and soft tissue cellulitis, but has also been reported as a cause of fasciitis as well as peritonitis. Staphylococcus lugdunensis has been reported as a cause of endometritis but has not been previously isolated from amniotic fluid. Here, amniotic fluid samples were collected in the course of a larger study on amniotic fluid bacteriology, with prior ethical approval and informed patient consent. Amniotic fluid was obtained at Caesarean Section by direct needle aspiration from the intact amnion. Analysis with Staphylococcal API test kits led to identification of Staphylococcus lugdunensis in two cases. The clinical significance of the finding in these reported cases is undetermined. Staphylococcus lugdunensis has been shown to be a cause of serious and potentially fatal morbidities, but this is the first report of its culture from amniotic fluid. As caesarean delivery is accepted as the single most important factor associated with post-partum infectious complications in both mother and neonate, the identification of this pathogen is a new concern.     

Eukaryote-Made Thermostable DNA Polymerase Enables Rapid PCR-Based Detection of Mycoplasma,Ureaplasma and Other Bacteria in the Amniotic Fluid of Preterm Labor Cases

Background

Intra-amniotic infection has long been recognized as the leading cause of preterm delivery. Microbial culture is the gold standard for the detection of intra-amniotic infection, but several days are required, and many bacterial species in the amniotic fluid are difficult to cultivate.

Methods

We developed a novel nested-PCR-based assay for detecting Mycoplasma, Ureaplasma, other bacteria and fungi in amniotic fluid samples within three hours of sample collection. To detect prokaryotes, eukaryote-made thermostable DNA polymerase, which is free from bacterial DNA contamination, is used in combination with bacterial universal primers. In contrast, to detect eukaryotes, conventional bacterially-made thermostable DNA polymerase is used in combination with fungal universal primers. To assess the validity of the PCR assay, we compared the PCR and conventional culture results using 300 amniotic fluid samples.

Results

Based on the detection level (positive and negative), 93.3% (280/300) of Mycoplasma, 94.3% (283/300) of Ureaplasma, 89.3% (268/300) of other bacteria and 99.7% (299/300) of fungi matched the culture results. Meanwhile, concerning the detection of bacteria other than Mycoplasma and Ureaplasma, 228 samples were negative according to the PCR method, 98.2% (224/228) of which were also negative based on the culture method. Employing the devised primer sets, mixed amniotic fluid infections of Mycoplasma, Ureaplasma and/or other bacteria could be clearly distinguished. In addition, we also attempted to compare the relative abundance in 28 amniotic fluid samples with mixed infection, and judged dominance by comparing the Ct values of quantitative real-time PCR.

Conclusions

We developed a novel PCR assay for the rapid detection of Mycoplasma, Ureaplasma, other bacteria and fungi in amniotic fluid samples. This assay can also be applied to accurately diagnose the absence of bacteria in samples. We believe that this assay will positively contribute to the treatment of intra-amniotic infection and the prevention of preterm delivery.     

The PGE2 vaginal film: An alternative to conventional induction in multiparae with poor cervical scores

In a study involving 50 multiparous subjects with poor cervical scores (⪕3), induction of labour by conventional amniotomy and oxytocin was compared with preinduction cervical ripening using a single administration of prostaglandin E₂ (850ug) in a new vaginal film formulation. Indications for elective delivery, maternal characteristics and distribution of cervical scores in the two groups were similar. Significant changes in mean cervical score were achieved within 12 hours of film insertion. In this group, 11 subjects (45.8%) established labour within 12 hours and a further 8(33.3%) did so before 24 hours so that only 5 cases required amniotomy and oxytocin. Instrumental delivery was less in this group and none of these subjects required Caesarean section for a failure of induction. No adverse maternal or fetal side effects were observed. Convenience, ease of administration and stability of this new prostaglandin formulation make it a useful alternative to conventional induction of labour in the multiparous patient with a poor cervical score.     

Measuring fetal and maternal temperature differentials: a probe for clinical use during labour

The healthy fetus maintains a higher temperature than that of its mother during gestation and labour. This results from the thermal balance between the heat generated by the fetus and the heat loss to its maternal surroundings. The heat loss can be by heat exchange via blood flowing in the umbilical cord and placenta, and via conduction through the fetal skin and amniotic fluid to the maternal wall. The temperature difference between the fetal and maternal tissue may reflect the metabolic state of the fetus and the magnitude and changing patterns of placental blood flow during labour. Physiological changes, such as those induced by epidural analgesia, and fetal infection have been shown to exhibit an increase in the absolute temperature. An intrauterine probe, previously used for non-invasive ECG detection, has been equipped with temperature sensors that measure fetal and maternal skin temperature in utero. Laboratory tests to characterize the performance of the probe reveal that absolute and differential temperatures can be resolved to around 0.01° C with a thermal time constant of approximately 9 s. Ideally the probe body should have infinite thermal insulation or thermal shunting across the probe will occur reducing the measured temperature difference. In this initial probe design, a high thermal isolation between sensors has been achieved but is not perfect, resulting in around 85% of the actual temperature difference across the probe being registered. Average feto-maternal differences of 0.2° C have been measured in a clinical investigation.     

Bubble Stability Test Compared with Lecithin Assay in Prediction of Respiratory Distress Syndrome

A simple test for surfactant, utilizing bubble stability in ethanol, was performed in 106 samples of amniotic fluid obtained from 94 patients. Of these patients 80 delivered within 48 hours of the collection of the sample. The results were compared with the lecithin concentration in the same amniotic fluid samples and with the quality of respiration in the neonate. The test was “positive,” indicating fetal pulmonary maturity, in 37 cases and none of these infants developed respiratory distress syndrome (R.D.S.). In only one of these cases, however, was gestation less than 37 weeks. The test was “intermediate” or “negative” in 43 cases but in 35 of these infants respiration at birth was perfectly normal.Performed by the method described by its originators, this simple test gives too many false negative results to be of value in routine clinical practice, although a positive result is helpful. The concept of the test is ingenious, however, and further developments may be expected.     

The Salivary Scavenger and Agglutinin (SALSA) in Healthy and Complicated Pregnancy

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. The etiology is not clear, but an immune attack towards components of placenta or fetus has been indicated. This involves activation of the complement system in the placenta. We have previously described the presence of the complement-regulating protein salivary scavenger and agglutinin (SALSA) in amniotic fluid. In this study we investigated the potential role of SALSA in pregnancy by analyzing its presence in amniotic fluid and placental tissue during healthy and complicated pregnancies. SALSA levels in amniotic fluid increased during pregnancy. Before 20 weeks of gestation the levels were slightly higher in patients who later developed pre-eclampsia than in gestation age-matched controls. In the placenta of pre-eclamptic patients syncytial damage is often followed by the formation of fibrinoid structures. SALSA was found clustered into these fibrinoid structures in partial co-localization with complement C1q and fibronectin. In vitro analysis showed direct protein binding of SALSA to fibronectin. SALSA binds also to fibrin/fibrinogen but did not interfere with the blood clotting process in vitro. Thus, in addition to antimicrobial defense and epithelial differentiation, the data presented here suggest that SALSA, together with fibronectin and C1q, may be involved in the containment of injured placental structures into fibrinoids.     

Strip test for bedside detection of interleukin-6 in cervical secretions is predictive for impending preterm delivery

Inflammatory cytokines in amniotic fluid are markers of prematurity which could characterize preterm labour of infectious origin. To avoid amniocentesis, we analyzed IL-6, IL-8, IL-10, and IL-13 by RT-PCR in cervical secretions (CS) of 307 women with preterm labour. IL-6 was detected in 26.3% patients who delivered at less than 34 weeks (specificity: 95.8%). In addition, IL-6 was associated with delivery within 7 days (specificity: 91.6%). To render the detection more rapid and cheaper, a strip test was designed and evaluated comparatively with RT-PCR in 76 women. This bedside strip test was twice more sensitive than RT-PCR, with little decrease in specificity.     

Evaluation of a competitive binding assay for cortisol using horse transcortin

A non-chromatographic competitive binding assay (CBA) using horse transcortin has been employed in the routine measurement of cortisol in plasma, urine and amniotic fluids. Comparing the values with those of a radioimmunoassay (RIA) or a fluorimetric method (FM) an excellent correlation between the three methods both in plasma and urine has been calculated in normal subjects and in patients with various endocrine disorders. In amniotic fluids, however, there were discrepancies between CBA and RIA. Whereas CBA showed no differences, RIA gave significantly higher values in amniotic fluids of female than of male fetuses. Elevated free plasma cortisol levels observed in patients with prostatic cancer after diethyl stilboestrol diphosphate therapy did not correlate with unconjugated urinary cortisol concentration as measured with CBA and FM. In newborns, a relatively high plasma level found 12 hours after birth was followed by a nadir on the 2nd and 3rd day of life and by an increase until levels of adults on the 5th day of life were reached.     

Effectiveness of pain relief in labour: survey of 1000 mothers

The amount of pain that had been experienced by 1000 women during vaginal delivery of a live child was determined by interview within 48 hours of delivery. Patients had been offered a choice of analgesia, and 536 had received epidural analgesia: pain relief was greatest in this group, just over half having had a painless labour. The duration of pain was also reduced by a third in this group even though patients who had received an epidural block had tended to have longer labour and an incidence of assisted delivery of 51% compared with 6% in the remainder. Seventy-two per cent of the patients receiving an epidural had had as much pain as they had expected. A similar proportion (70%) was reported with simpler analgesic methods, suggesting that women may expect a certain amount of pain in labour and request further analgesic treatment when this is exceeded.     

Active Management of Labour

Active management of labour has been developed to the extent that an assurance is given to every woman who attends this hospital that her first baby will be born within 12 hours. This assurance could lead to a welcome change in present attitudes because the mere prospect of prolonged labour is often a cause of serious concern during a first pregnancy. Labour of strictly limited duration makes it possible to provide every woman with a personal nurse, and it places the problem of pain in a new setting.The results of a prospective study of 1,000 consecutive primigravidae are presented, and the guidelines to a standard policy of management are defined. Difficulty in meeting the commitment to early delivery arose almost exclusively in cases in which the diagnosis of labour was in doubt; only seven women were retained in the delivery unit for 12 hours.     

The Role Played by Rh Immunization in Pregnancy Wastage

In about 50% of sensitized pregnancies viable infants were not produced when Rh immunization was allowed to run its natural course. In the past 25 years, five major advances have been made in this area of interest: (1) discovery of the Rhesus factor; (2) development of the technique of exchange transfusion; (3) selective premature induction of labour; (4) spectroscopic examination of amniotic fluid; and (5) prenatal treatment by intrauterine transfusion. Virtually all pregnancy wastage due to Rh immunization is now theoretically preventable through the use of these tools.     

Location,location, location: larvae position inside the nest is correlated with adult body size in worker bumble-bees (Bombus impatiens)

Social insects display task-related division of labour. In some species, division of labour is related to differences in body size, and worker caste members display morphological adaptations suited for particular tasks. Bumble-bee workers (Bombus spp.) can vary in mass by eight- to tenfold within a single colony, which previous work has linked to division of labour. However, little is known about the proximate mechanism behind the production of this wide range of size variation within the worker caste. Here, we quantify the larval feeding in Bombus impatiens in different nest zones of increasing distance from the centre. There was a significant difference in the number of feedings per larva across zones, with a significant decrease in feeding rates as one moved outwards from the centre of the nest. Likewise, the diameter of the pupae in the peripheral zones was significantly smaller than that of pupae in the centre. Therefore, we conclude that the differential feeding of larvae within a nest, which leads to the size variation within the worker caste, is based on the location of brood clumps. Our work is consistent with the hypothesis that some larvae are ‘forgotten’, providing a possible first mechanism for the creation of size polymorphism in B. impatiens.     

The kinetics of extraamniotically injected prostaglandins to induce midtrimester abortion

In an attempt to improve the extraamniotic administration of prostaglandins in effecting abortion, the movement of injected prostaglandins in a high or low viscosity medium has been observed by radiological studies and radioimmunoassay of PGE and PGFα in amniotic fluid and maternal plasma in association with intrauterine tocographic responses.Results obtained suggest that the immediate response by the uterus is a reflection of the speed of absorption of prostaglandins from the chorio-decidual space and that this influences the outcome in inducing abortion within 24 hours. By giving the prostaglandins in a viscous medium a slower release of prostaglandins was produced in most cases, which probably accounts for the greater efficacy obtained using single injections of prostaglandins in this vehicle compared with normal saline.     

Etude clinique préliminaire sur l'emploi de la dihexyvérine en obstétrique

This study attempted to evaluate the effect of dihexyverine HCl (Metaspas), an anticholinergic and direct smooth muscle relaxant (spasmolytic), in shortening the first stage of labour. One hundred and five patients constituted the series: 31 were primiparae, 27 secundiparae and 47 multiparae. The majority of these (95) received one intramuscular injection (10 mg.) of dihexyverine. Alphaprodine (Nisentil), 40 mg., was administered in all but 10 cases, since dihexyverine has no analgesic action. Seventy-five control patients were used: 25 were primiparae, 25 secundiparae and 25 multiparae. Alphaprodine alone was administered to these control patients. The length of time for dilatation from 4 cm. to 10 cm. was the selected criterion. In the control group, the average time for complete cervical dilatation was 4 hours, 10 minutes. In the group treated by dihexyverine, complete dilatation was achieved in 1 hour, 16 minutes. On the average, the first stage of labour was 2 hours and 54 minutes shorter with dihexyverine; the clinical effect begins 10-30 minutes after administration. The only side effect encountered was a skin rash in one patient.     

Patients' attitudes to induction and labour.

An attempt was made to ascertain patients'' attitudes towards planned induction and labour. Twenty per cent of patients had not heard of induction before their pregnancy, and those who had had most probably heard about it from relations and friends rather than the media. Most patients had no firm opinions on induction of labour but were usually glad to have their pregnancy ended. Many considered that they had not been given enough information by the medical staff on their induction. The amount of pain experienced by patients at amniotomy was related to the "favourability" of the cervix. Possibly women with a low cervical score should be given more premedication or inhalation analgesia at amniotomy. Most patients found injections of narcotic agents adequate analgesia in labour. Those patients who did not receive adequate analgesia were principally those who had either very short or quite long labours. Patients with long labours may benefit from more liberal use of analgesia, but no satisfactory form of analgesia seems to be available for patients who are likely to deliver within two or three hours of induction.     

The influence of gestational age and onset of labour on determinants of fetal-maternal fluid and electrolyte balance in sheep.

Our aim was to compare the effects of gestational age and the timing of the onset of labour on factors influencing fetal fluid and electrolyte balance and urine production in fetal sheep. We measured the volume and composition of fetal urine and amniotic and allantoic fluids, as well as fetal and maternal plasma composition and micturition episodes in sheep during late gestation until the onset of labour. We found that daily fetal urine production and urethral urine flow per micturition episode increased significantly in relation to the onset of labour but not to gestational age (P < 0.05). In the 2 days preceding the onset of labour fetal urine and amniotic fluid K+ concentrations and urine osmolality increased significantly and the Na+/K+ ratio in allantoic fluid decreased significantly (P < 0.05). There was also a significant fall in fetal arterial SaO2 (P < 0.05) but no significant changes occurred in fetal plasma electrolyte composition, osmolality or AVP concentrations. Fetal plasma cortisol and prolactin concentrations and amniotic and allantoic fluid prolactin concentrations increased significantly and progressively in association with both advancing gestation and the onset of labour whereas maternal plasma prolactin concentrations increased significantly only in the 2 days before the onset of labour (P < 0.05). We conclude that some developmental aspects of fetal fluid and electrolyte balance, including renal function, are more closely related to the timing of parturition than to gestational age per se.