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Initial permeability of the 19-day foetus to nickel.

The administration of 63NiCl2 to 19-day pregnant rats produced a limited transfer of nickel to the foetus. An experimental model based on the incubation of the conceptuses still connected to the maternal organism resulted in an appreciable net transfer of nickel through the amniotic membranes. The placenta retained a significant amount of radioactive nickel as did the lining of the uterine wall. The circulation of nickel through the foetus following the direction maternal blood----placenta----foetus----amniotic membranes----endometrium----maternal venous blood, is postulated. This transfer could provide an additional protection to placental barrier against metal toxicity.

Animals↗

[Management of total placental retention with oxytocin injected into the umbilical vein].

Oxytocin was injected into the umbilical vein in 8 patients whose third stage of labor was complicated by retention of the placenta. The placenta was delivered in all patients within 3 min after the injection, avoiding thus the need for manual removal. This method seems to be effective, quick and safe in the management of retained placenta, and decreases the risks associated with the use of anesthesia and puerperal complications such as infection or trauma to the uterus.

Adult↗

Failure of conservative management of placenta previa-percreta.

We present a patient with a placenta previa in which we failed to manage conservatively with methotrexate and uterine embolization. The patient was diagnosed in the second trimester as having a possible placenta previa-increta,and underwent a repeat classical cesarean delivery at 32 weeks of gestation due to significant antepartum vaginal bleeding. Following abdominal closure,the uterine vessels were embolized with the Gel-Foam by interventional radiology. The placenta previa was left in-situ and patient was discharged home in stable condition in five days. The patient reported on the 44th postoperative day with heavy vaginal bleeding. A total abdominal hysterectomy was performed due to an unstable patient's hemodynamic condition in association with fluid resuscitation and multiple blood transfusions. The pathologic findings revealed a 675 g uterus with placenta previa-percreta with extension of chorionic villi to the serosal layer. Our case demonstrates a need for careful selection of patients with placenta previa and suspected accreta/increta/percreta that would be suitable candidates for conservative medical management. Patients who opt for conservative medical management should be informed about the possibility of catastrophic bleeding associated with a retained placenta, that would ultimately require blood transfusions and hysterectomy.

Adult↗

Randomized trial of intraumbilical vein oxytocin in midtrimester pregnancy losses.

OBJECTIVE: The purpose of this double-blind prospective randomized trial was to determine whether high-dose intraumbilical vein oxytocin injection shortens the third stage of labor in midtrimester pregnancy losses. STUDY DESIGN: Patients (n = 50) with spontaneous or induced midtrimester pregnancy losses (14 to 26 weeks' gestation) were randomized to receive either 100 IU of oxytocin in 20 ml of normal saline solution or 20 ml of normal saline solution alone as a placebo. The umbilical vein was injected as soon as the cord was clamped. Outcome data were collected. RESULTS: Of the 50 patients randomized, 45 completed the study. Five were excluded after randomization because of either cesarean delivery (1 patient) or en caul delivery (4 patients). Twenty-one patients received oxytocin, and 14 received placebo. Ten patients who were not injected because of technical failure were evaluated separately. There were no differences between the three groups with regard to gestational age, fetal weight, length of the third stage, blood loss, or need for operative removal of the placenta. CONCLUSION: Injection of high-dose oxytocin into the umbilical vein in second-trimester pregnancy losses does not shorten the third stage of labor or decrease the need for surgical intervention because of retained placenta.

Abortion, Spontaneous↗

The role of endogenous estrogens in the maturation process of the bovine placenta.

The plasma estrogen and progesterone concentrations of 19 pregnant cows (average duration of pregnancy 266.0 +/- 2.3 d at the start of the study) were determined daily from Day 6 pre partum to Day 1 post partum. Parturition was induced in all cows by administration of 10 mg i.m. flumethasone. Values were centered around the delivery date (Day 0) following either induced normal calving (n = 3) or surgical delivery (n = 16). In animals showing spontaneous expulsion of the fetal membranes (Group 1, n = 6) the average total estrogen concentration increased significantly from Day 6 until Day 1 before parturition (1329.2 +/- 317.9 to 3719.8 +/- 951.2 pg/ml in total estrogens). A marked decrease was observed on Day 1 post partum (459.4 +/- 344.2 pg/ml). In comparison with Group 1, animals showing either a delayed or partial expulsion of the fetal membranes, or in which the placenta could be withdrawn 16 h after calving (Group 2, n = 5), had consistently lower total estrogen concentrations between Day 6 (595.4 +/- 174.8 pg/ml) and Day 1 (1884.3 +/- 565.1 pg/ml) before parturition. The estrogen values of the cows with retained placenta (Group 3, n = 8) from Days 6 to 0 pre partum were significantly lower than those of Group 2. Total estrogen concentrations of the three groups 1 d post partum did not differ significantly. It is generally recognized that estrogens play an important role in the maturation process of the placentomes. Our investigation demonstrates that not only is the magnitude of the prepartum rise in estrogens of great influence of the maturation process but the duration of this rise is likewise important. These two factors are vital for a normal expulsion of the fetal membranes.

Journal Article↗

Influence of the foetus, placenta and ovary on the mammotrophic activity of pregnant rat serum.

Serum mammotrophic activity was assayed using an organ culture technique with histological endpoints. Using sera of 13 days pregnant rats with 1 to 18 conceptuses, activity was detectable even in the presence of 1 conceptus, but the activity with 1-4 conceptus(es) tended to be less than with 6-18. Serum of rats with 1-3 conceptus(es) was approximately 2-4 times less active than serum of rats with 14 conceptuses. Removal of the conceptuses on day 15 caused loss of mammotrophic activity of the serum, tested 4 days later. When the foetuses, the ovaries or both the foetuses and ovaries were removed on day 15 of pregnancy, mammotrophic activity was present in the serum collected 4 days later. Differences in activity between the treated groups were small. The mammotrophic activity was comparable to the activity of serum of untreated 15 days pregnant rats or 19 days sham-operated pregnant rats. Explanted single fragments of a 19 days pregnant rat placenta released activity into the medium. The placenta retained this capicity even when the foetus had been removed 4 days previously.

Animals↗

Human placental transfer and metabolism of p-aminobenzoic acid.

Studies in our laboratory have shown that the N-acetylation activity of the human term placenta is a predominantly attributable to the NAT1 form of arylamine N-acetyltransferase (NAT). To further assess the acetylation capacity of the placenta, the N-acetylation of the prototype NAT1-selective substrate, p-aminobenzoic acid (PABA), was studied using the in vitro human placental perfusion model. This study compared the net N-acetylation of PABA in intact placental tissue with the PABA acetylation activity observed in a subcellular fraction (cytosol). Such studies with intact tissue can permit assessment of the exposure of the fetus in vivo to drugs and their metabolites. Acetylated metabolite (N-acetyl-p-aminobenzoic acid) was detectable in fetal and maternal venous samples taken less than 5 min from the start of perfusion with PABA. In a closed recirculating system, the rate of placental PABA transfer decreased as PABA concentrations equilibrated across the placenta. In contrast, the rate of N-acetyl-p-aminobenzoic acid formation continued to increase throughout the entire time of perfusion. Kinetic parameters of PABA N-acetylation measured in cytosol prepared from perfused placental tissue show that the placenta retains its ability to N-acetylate PABA at fresh tissue levels even after 6 hr of in vitro perfusion (Vmax = 5.75 +/- 0.42 nmol/min/mg (fresh) vs. Vmax = 7.24 +/- 0.31 nmol/min/mg (perfused); mean +/- S.E.M., n = 6). These studies indicate that the human placenta has a significant capacity to N-acetylate NAT1-selective substrates of NAT and that it maintains its ability to metabolize xenobiotics during in vitro perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobenzoic Acid↗

Dropsy of the fetal sacs in mares: induced and spontaneous abortion.

Eight cases of severe dropsy of the fetal sacs have been observed in mares. All were in multiparous mares whose ages ranged from five to 20 years and who were 7 1/2 to 10 3/4 months pregnant. Abortion started spontaneously in four cases and had to be induced in the remaining four by manual dilation of the cervix, rupture of the tough allantochorion and the siphoning off of 120 to 220 litres of allantoic fluid. The amnion was normal. Dystocia, due to uterine inertia, occurred in all eight cases, one hydrocephalic fetus needing fetotomy. All fetuses were alive at delivery although four were teratologically deformed and two were markedly underdeveloped. None survived. Retention of a somewhat oedematous placenta occurred in six cases. Microscopic examination of the placenta showed some evidence of degeneration, but none of inflammatory change. One mare died, seven recovered rapidly. One mare was served again and gave birth to a living foal. Special care needs to be given to pre- and post-operative shock, retained placenta and delayed involution.

Abortion, Induced↗

Pharmacologic management and controlled cord traction in the third stage of labour.

Active management of the third stage of 62 944 labours over a period of 15 years (1970-84) constituted an intramuscularly administered combination of ergometrine (0.2 mg) and oxytocin (5 units), and controlled cord traction as mechanical assistance in delivery of the placenta. By these means manual removal of the placenta was performed in 0.67% of all deliveries, uterine inversion was found in 5 cases (1 in 12 588 deliveries) and blood transfusion necessary in 1.67% of all deliveries during puerperium. Oxytocin injection of 40-100 units into the umbilical vein of the retained placenta was performed in 40 cases. In 12 (30%) of these cases the placenta was separated by this new method. Previous use of intrauterine devices was a new etiological factor in the abnormally adherent placenta.

Adult↗

Management of the third stage of labour in women at low risk of postpartum haemorrhage.

OBJECTIVE: To compare active management with physiological management of the third stage of labour in women at low risk of postpartum haemorrhage. DESIGN: Randomised allocation of women in labour at low risk of postpartum haemorrhage to either physiological or active management of the third stage. SETTING: Labour ward in a district general hospital. PATIENTS: 193 Women with spontaneous vaginal delivery at term completed the study. Exclusion criteria were induction or augmentation of labour, antepartum or previous postpartum haemorrhage, premature rupture of membranes, previous caesarean section, raised blood pressure, cervical lacerations and third degree tears. INTERVENTIONS: Active management with syntometrine and controlled cord traction; or physiological management, where the cord was not clamped and the placenta was delivered by maternal effort. MEASUREMENTS: Blood loss was measured subjectively at delivery and estimated objectively by comparing the haemoglobin in labour with that on the third postpartum day. The duration of the third stage was also measured as was the incidence of retained placenta and blood transfusion. RESULTS: There was no significant difference in the estimated blood loss or haemoglobin drop between the two groups (P > 0.5). In addition the duration of the third stage was significantly longer in the physiological group (P < 0.001). Out of 90 women having physiological management, 7 received oxytocics for presumed postpartum haemorrhage. Only one case in the active group required further oxytocics and one other case in this group required a manual removal of placenta. CONCLUSIONS: This preliminary study confirms that active management results in a reduction in the length of the third stage of labour. However, it suggests that active management does not reduce blood loss when compared to physiological management in the woman at low risk of postpartum haemorrhage.

Delivery, Obstetric↗

Placental copper transport in the rat. II: Effect of maternal copper deficiency.

Copper (Cu) placental transport presents a steep downhill gradient from mother to fetus. This process could be altered by low-molecular-weight (LMW) ligands and maternal Cu deficiency. We compared the ratio of Cu transfer from dam-to-fetus in Cu-deficient (CuDf) and Cu-sufficient (CuSf) rats in the last day of gestation. Anaesthetized dams were iv injected 79 mumol/kg (5 mg/kg) of either Cu acetate [Cu (AcO)2]; Cu+L-histidine, 1:10. [Cu(His)10]; Cu-(glycyl-glycyl-L-histidine) [Cu(GGH)], or saline. Dam and fetal blood, as well as placentae were obtained at 0, 10, 20, 40 and 60 min. At time 0, CuDf dams had lower plasma Cu than CuSf dams (8.3 +/- 1.2 versus 26.7 +/- 1.1 mumol/l), but CuDf fetuses plasma Cu was unchanged. This resulted in a more favourable mean fetal: maternal plasma Cu ratio in the CuDf fetuses (0.61) than in the CuSf fetuses (0.21). Dam plasma Cu was unaffected by the chemical form of Cu injected. In CuDf fetuses lower plasma Cu was observed with Cu(GGH) and Cu (His)10 at 20 min than in the CuSf. In the presence of these LMW ligands CuDf placentae retained more Cu than those of the CuSf group. CuDf was associated ultrastructurally with extensive lipid deposition in dam hepatocytes and, to a lesser extent, in CuDf fetal liver. These results indicate that in CuDf, LMW ligands increase placental uptake of Cu, without improving placenta-fetus transport. Although the rat fetus is well adapted to intrauterine CuDf, it may also be susceptible to hepatic lipid infiltration when the dam is CuDf.

Animals↗

Childbirth in rural areas: maternal deaths, village deliveries and obstetric service use.

We explored village maternal deaths in an area of the East Sepik Province of Papua New Guinea where most women delivered at home. Postpartum haemorrhage, retained placenta and puerperal sepsis were common causes of death. Follow-up of a group of pregnant women showed that abnormal labour was frequent. 24% of multigravidae (95% CI 17-33) reported a labour that lasted longer than 24 hours. In 9% of all births (95% CI 5-15) the third stage lasted longer than one hour, or products were retained. Despite a high proportion of obstetric complications in apparently low-risk villages births, few women attend a health facility for delivery. Health centre attenders were a relatively privileged group. Some hospital users complained about staff attitudes. A poor reputation means that women are less likely to use health services for delivery. Providers need to improve the acceptability of the care provided, and communities should be encouraged to help with transport for their women to go to a health facility when they are in labour.

Community Health Services↗

Labor induction after fetal death. A retrospective analysis.

OBJECTIVE: To describe the delivery outcomes in patients with stillborn infants after labor induction versus spontaneous onset of labor. STUDY DESIGN: A retrospective chart review was performed of singleton pregnancies complicated by fetal death over a three-year period when awaiting spontaneous onset of labor was a common practice. Exclusion criteria were prior multiple cesarean deliveries, placenta previa, preeclampsia or suspected abruptio placentae. Outcome measures included time spent in the labor and delivery unit and rates of maternal hemorrhagic morbidity and endomyometritis. RESULTS: Two hundred eight patients, 100 patients undergoing labor induction and 108 with spontaneous onset of labor, met the study criteria. Patients delivering after induction spent a longer time in the labor and delivery unit (13.7 versus 4.4 hours). The endomyometritis rate was higher in the spontaneous labor group (6% versus 1%). There were no differences in the frequency of postpartum hemorrhage, retained placenta or need for blood transfusion. CONCLUSION: Induction following diagnosis of fetal death is safe and may reduce maternal infectious morbidity.

Adult↗

Electron microscopy of the placenta and related structures of the marmoset.

The marmoset has recently become an important animal in oncologic research, especially with respect to herpes deoxyribonucleic acid viral tumors. As a prototype of the primitive New World monkey, it is also valuable for the study of primate evolution. For these reasons this ultrastructural description of its placenta is presented, including the first electron micrographs of the basal plate and amnion. The main placental mass is pseudo-labyrinthine, or trabecular. The ultrastructural features of the cellular and syncytial trophoblast and endothelium closely resemble those of higher primates. The junctional region shows numerous clumps of moderately well-differentiated trophoblast, an acellular junctional zone, and a poorly developed decidual reaction. Trabecular connective tissue is sparser and transitional trophoblastic elements are less prominent than those in the human placenta. The amnion is ultrastructurally indistinguishable from that of the higher primates. Although the marmoset's placenta retains certain primitive gross and histologic features, such as the large persistent yolk sac and the trabecular condition, it is ultrastructurally quite similar to that of man.

Amnion↗

For a systematic policy of i.v. oxytocin inducted placenta deliveries in a unit where a fairly active management of third stage of labour is yet applied: results of a controlled trial.

The authors analysed the effect of the i.v. oxytocin induced third stage of labour in a controlled trial concerning 1000 patients. The appliance of such an policy in a unit that already had a fairly active management of delivery was very encouraging. The incidence of post-partum haemorrhage (greater than 500 ml) is significantly (P less than 0.001) less than in the control group; and the same for severe haemorrhage. The third stage is significantly (P less than 0.001) shorter in the oxytocin-injected group than in the control group. Moreover, there is no significant difference between the two groups for retained placenta. The economy of blood transfusion, which is a major concern nowadays, could be the real interest of this active management of the third stage of labour.

Female↗

Effect of a failure of energy supply on adenine nucleotide breakdown in placentae and other fetal tissues from rat and guinea pig.

The effects of ischaemia on adenylate energy charge of tissues from fetal rats and fetal guinea pigs were measured. Adult rat and guinea-pig tissues, as well as human placentae, were also studied. The largest differences observed were between the fetuses from different pregnant animals (P = 4.74 X 10(-15). Reductions in energy charge in placentae were slower than in other defined fetal tissues, especially brain. In the rat, an immature species at birth, greater 'stability' was observed in placentae of 14 days of gestation than near term at 20 days of gestation. As contrast, in the guinea pig, a mature species at birth, there was no difference in 'stability' in placenta or other fetal tissues between about 40 days of gestation and near term, about 60 days of gestation. In addition to these tissue and maturity effects in the fetus, it has been confirmed that fetal tissues are more 'resistant' than adult tissues to failures of energy supply. Concentrations of adenosine, uridine, guanosine and cytidine nucleotides in placenta show similar patterns in rats and guinea pigs. Fetal liver contains more uridine nucleotides and brain more cytidine nucleotides. It is suggested that the placenta retains an early fetal ability to maintain itself during ischaemia; this might be advantageous during parturition. Possible endocrine and other mechanisms 'damping' fetoplacental metabolism are linked with a discussion of the large maternal effect.

Adenine Nucleotides↗

Endemic placenta accreta in a population of remote villagers in Papua New Guinea.

Using a combination of prospective registration of definite cases (n = 47) and retrospective identification of probable cases (n = 22) over a 6.5-year period, we have estimated that the rate of placenta accreta in the Milne Bay Province of Papua New Guinea is at least 1.6 per 1000 births, and probably in excess of 2.3 per 1000. This is substantially higher than other reported estimates of the frequency of this condition, which causes significant maternal morbidity. The study population of 130,000 consisted mainly of subsistence cultivators who live in remote hamlets, and included about 27,600 women between the ages of 15 and 49 years. A number of factors seem likely to be important in the aetiology of the condition in Milne Bay Province, including infection associated with previous childbirth and abortion. Over three-quarters of the cases would have been prevented if all women of para greater than or equal to 4 or with a history of retained placenta had used effective contraception. Better obstetric care, including early treatment of postpartum sepsis and incomplete abortion, may also help to reduce the frequency of placenta accreta in this population.

Female↗

Complementary roles of genes regulated by two paternally methylated imprinted regions on chromosomes 7 and 12 in mouse placentation.

Imprinted genes have prominent effects on placentation; however, there is limited knowledge about the manner in which the genes controlled by two paternally methylated regions on chromosomes 7 and 12 contribute to placentation. In order to clarify the functions of these genes in mouse placentation, we examined transcription levels of the paternally methylated genes, tissue differentiation and development and the circulatory system in placentae derived from three types of bi-maternal conceptuses that contained genomes of non-growing (ng) and fully grown (fg) oocytes. The genetic backgrounds of the ng oocytes were as follows: one was derived from the wild-type (ngWT) and another from mutant mice carrying a 13 kb deletion in the H19 transcription unit including the germline-derived differentially methylated region (H19-DMR) on chromosome 7 (ngDeltach7). Another set of oocytes was derived from mutant mice carrying a 4.15 kb deletion in the intergenic germline-derived DMR (IG-DMR) on chromosome 12 (ngDeltach12). Although placental mass was lower in the ngWT/fg placentae compared with that in the WT placentae, it was recovered in the ngDeltach7/fg placentae, but not in the ngDeltach12/fg placentae. The ngDeltach7/fg placental growth improvement was associated with severe dysplasia such as an expanded spongiotrophoblast layer and a malformed labyrinthine zone. In contrast, the ngDeltach12/fg placentae retained the layer structures with expanded giant cells, but their total masses were smaller with a normal circulatory system in order. Our findings demonstrate that the genes controlled by the two paternally methylated regions, H19-DMR and IG-DMR, complementarily organize placentation.

Animals↗