A decline in prolactin levels in amniotic fluid and decidua at term pregnancy after the initiation of labour

Prolactin is known to inhibit the production of prostaglandins, key substances in the initiation of labour. To explore a possible role of prolactin in human parturition, prolactin levels were therefore measured in amniotic fluid and decidua at full-term pregnancy. Prolactin levels in amniotic fluid before labour were about three times higher than those at labour and they tended to decrease with time during labour. Prolactin levels in decidua before labour were about twice as high as those at labour. These findings suggest a possible involvement of prolactin in human parturition.     

Initiation of parturition in the goat: evidence for control by foetal glucocorticoid through activation of placental C21-steroid 17alpha-hydroxylase.

Infusion of dexamethasone into chronically catheterized foetal kids induced delivery in 41--65 h. Changes in the concentrations of placental and ovarian steroids in the maternal circulation at dexamethasone-induced delivery mimicked those preceding spontaneous kidding at term; in both instances the peripheral concentration of progesterone fell and the concentration of oestradiol-17beta rose. The concentration of cortisol in the foetus was low at dexamethasone-induced delivery. Metabolism of pregnenolone, progesterone, 17alpha-hydroxyprogesterone and androst-4-ene-3,17-dione by extracts of foetal placenta was investigated in late pregnancy, after premature parturition induced with dexamethasone or prostaglandins and after spontaneous parturition at term. In placenta obtained before the onset of labour (or from animals induced to kid by administration of prostaglandins), the main product of progesterone metabolism was a 5beta-pregnane-3,20-diol. In contrast, placentae from animals in which the foetal level of glucocorticoid had been raised (after spontaneous parturition or by administration of dexamethasone to the foetus) were able to 17alpha-hydroxylate and progesterone was metabolized to 5beta-pregnane-3alpha/3beta,17alpha,20alpha-triols and 17alpha,20alpha-dihydroxypregn-4-en-3-one. The appearance of placental 17alpha-hydroxylase was correlated with raised maternal concentrations of 17alpha,20alpha-dihydroxypregn-4-en-3-one and androstenedione. The induction or activation of placental 17alpha-hydroxylase may represent the mechanism by which foetal glucocorticoid controls the onset of labour in the goat.     

Cerebrospinal fluid levels of acetylcholinesterase, monoamines and oxytocin during labour, parturition, vaginocervical stimulation, lamb separation and suckling in sheep

Acetylcholinesterase (AChE) activity, and concentrations of monoamines, monoamine metabolites and oxytocin (OT) were measured in the cerebrospinal fluid (CSF) of sheep during late pregnancy, labour, parturition, vaginocervical stimulation, lamb separation and suckling. Concentrations of AChE, 4-hydroxy-3 methoxyphenylethan-1,2-diol (MHPG) and OT were significantly elevated during labour and parturition. OT levels were also significantly raised in cycling ewes given vaginocervical stimulation. Separation of the ewes from their lambs (0.5-2 h) caused significant increases in AChE and MHPG, but not in OT. During suckling, following reunion of the ewes and lambs, concentrations of AChE and OT were significantly raised. The dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly lower in CSF during late pregnancy than during parturition and post-partum. Intravenous injections of OT which produced high circulating levels of this hormone in plasma produced significant, but very small, increases in concentrations of OT in the CSF. Our results show that in the sheep, labour, parturition, suckling and vaginocervical stimulation provoke a release of OT in the brain similar to that in the peripheral circulation. Changes in CSF levels of AChE and MHPG during labour, parturition and lamb separation, but not during vaginocervical stimulation, may be related to stress or hypertension.     

Parturition in goats: studies on the interactions between the foetus, placenta, prostaglandin F and progesterone before parturition, at term or at parturition induced prematurely by corticotrophin infusion of the foetus.

Relationships between foetal corticosteroid concentrations, utero-ovarian prostaglandin F (PGF) and maternal peripheral progesterone have been examined in detail in goats shortly before spontaneous parturition at term. Foetal corticosteroids increased during the last 13-11 days of gestation and particularly sharply during the last 3 days and even during advanced labour. About 24 h before parturition, acute releases of PGF were evident in the vein draining the pregnant uterine horn, and these corresponded closely to the time of luteal regression. Further release of PGF occured when progesterone declined to low levels, probably reflecting in the course of labour. The changes observed before premature parturition, induced by infusing ACTH into foetal goats, were similar except for the more rapid increase in foetal corticosteoid concentrations. Immature neonates born after ACTH treatment were viable, placental delivery was normal and lactogenesis occurred in the mothers indicating that the treatment promoted full expression of the critical perinatal events. The early, acute releases of PGF were ipsilateral to the ACTH-infused foetus and were luteolytic provided the corpora lutea were also on that side. Luteolysis failed or was abnormally delayed if the corpora lutea were contralateral and prolonged ACTH treatment of the foetuses in such cases caused foetal death probably because of premature failure of the placenta. Similar findings were noted if ACTH infusion of the foetus was accompanied by simultaneous progesterone treatment of the mothers in order block the induction of labour. It was suggested that placental changes occurring during foetal hypercortisolism might be caused by increased placental oestrogen synthesis and the effect of this on the foeto-maternal junction along with a stimulatory action on PG synthesis in the maternal placenta. Experimental disruption of the normal sequence of events, when labour was blocked by progesterone, proved to be lethal to the foetus if the loss of placental integrity progressed sufficiently. The chain of regulatory signals linking increased activity of the foetal adrenal with parturition thus appears to involve stimulation of oestrogen biosynthesis, PGF release from the maternal placenta and the start of physical changes at the placental junction. Provided the foetus and corpora lutea are ipsilateral, the early releases of PGF effect luteolysis and a withdrawal of progesterone from the maternal circulation. When progesterone concentrations are sufficiently low, labour is initiated and its progress reflected by further release of PGF. The control mechanisms, which also provide for the final maturation of the foetus, clearly enable a close synchronization of the various perinatal events which are essential for the transition from foetal to postnatal life.     

The mother–offspring dyad: microbial transmission,immune interactions and allergy development

The increasing prevalence of allergy in affluent countries may be caused by reduced intensity and diversity of microbial stimulation, resulting in abnormal postnatal immune maturation. Most studies investigating the underlying immunomodulatory mechanisms have focused on postnatal microbial exposure, for example demonstrating that the gut microbiota differs in composition and diversity during the first months of life in children who later do or do not develop allergic disease. However, it is also becoming increasingly evident that the maternal microbial environment during pregnancy is important in childhood immune programming, and the first microbial encounters may occur already in utero. During pregnancy, there is a close immunological interaction between the mother and her offspring, which provides important opportunities for the maternal microbial environment to influence the immune development of the child. In support of this theory, combined pre‐ and postnatal supplementations seem to be crucial for the preventive effect of probiotics on infant eczema. Here, the influence of microbial and immune interactions within the mother–offspring dyad on childhood allergy development will be discussed. In addition, how perinatal transmission of microbes and immunomodulatory factors from mother to offspring may shape appropriate immune maturation during infancy and beyond, potentially via epigenetic mechanisms, will be examined. Deeper understanding of these interactions between the maternal and offspring microbiome and immunity is needed to identify efficacious preventive measures to combat the allergy epidemic.     

Steroids in the amniotic fluid of the rhesus monkey (Macaca mulatta).

Representative C21, C19 and C18 steroids have been measured in the amniotic fluid and maternal femoral plasma of rhesus monkeys during the last 50 days of pregnancy. The concentrations of cortisol, progesterone, androstenedione, oestrone sulphate all increased in amniotic fluid before spontaneous parturition. In contrast, amniotic fluid oestradiol levels remained low and unchanged, and were always less than the concentrations in the maternal plasma. The changes in progesterone, cortisol and oestrone concentrations in amniotic fluid occurred independently of significant changes in the concentration of these steroids in the maternal plasma. Betamethasone administered to monkeys after day 150 of pregnancy suppressed amniotic fluid and maternal plasma cortisol. This treatment markedly suppressed the concentration of progesterone in amniotic fluid, but did not alter its concentration in maternal plasma. It is concluded that during late pregnancy in the rhesus monkey there is an increase in the concentration of some steroids in amniotic fluid independent of alterations in their concentrations in maternal plasma. These changes could reflect an increase in foetal adrenal steroid secretion.     

Corticotrophin-releasing hormone and ACTH levels in maternal and fetal blood during spontaneous and oxytocin-induced labour

The changes in corticotrophin-releasing hormone (CRH), ACTH and dehydroepiandrosterone (DHEA) in maternal and fetal plasma were estimated in women undergoing spontaneous and oxytocin-induced labour to correlate hormone changes with the mode of parturition. Blood was sampled from a maternal peripheral vein 2 days before labour, during the second stage of labour and on the second postnatal day, and also from umbilical vessels just after delivery. Hormone concentrations were measured by RIA and ELSA methods. The maternal plasma CRH concentration before labour was significantly higher in the group of women delivered spontaneously and declined during the labour through to the second postnatal day. Measured in umbilical vessels, CRH as well as ACTH concentrations were higher in the umbilical vein than artery. The mean maternal plasma ACTH was similar in both groups before delivery, then increased significantly in both groups during the labour, decreasing on the second day after delivery. There were no changes in DHEA concentrations among the groups and at all time points of collection. No correlations between CRH and ACTH or DHEA were observed. Our results suggest that the maternal pituitary can respond to stress factors during delivery but peripheral CRH, probably mainly of placental origin, is not a major modulator of pituitary action.     

Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity—A systematic review,meta‐analysis,and meta‐regression

Polycystic ovary syndrome (PCOS) is associated with an increased risk of maternal pregnancy and delivery complications. However, the impact of clinical features of PCOS and other potential risk factors in PCOS is still unknown. We aimed to investigate the association of PCOS with maternal pregnancy and delivery complications with consideration of risk factors and potential confounders. The meta‐analysis included 63 studies. PCOS was associated with higher miscarriage, gestational diabetes mellitus, gestational hypertension, pre‐eclampsia, induction of labour, and caesarean section. The association of PCOS with these outcomes varied by geographic continent, PCOS phenotypes, and study quality. Pre‐eclampsia and induction of labour were not associated with PCOS on body mass index‐matched studies. No outcome was associated with PCOS on assisted pregnancies. Age was significantly associated with higher miscarriage on meta‐regression. There were no studies assessing perinatal depression. We confirm that PCOS is associated with an increased risk of maternal pregnancy and delivery complications. The association of PCOS with the outcomes is worsened in hyperandrogenic PCOS phenotypes, in specific geographic continents, and in the highest quality studies but disappears in assisted pregnancies. Future studies in PCOS are warranted to investigate proper timing for screening and prevention of maternal pregnancy and delivery complications with consideration of clinical features of PCOS.     

Clinical Review 160: Postpartum autoimmune thyroid disease: the potential role of fetal microchimerism

Fetal microchimerism is defined as the presence of fetal cells in maternal tissues established during pregnancy. Immune suppression of maternal immunity during pregnancy by the placenta may play an important role in allowing the establishment of such fetal microchimerism. However, peripheral blood fetal microchimerism that persists in the postpartum period is considered a natural event and implies the induction of tolerance during pregnancy. Identification of fetal cells that persist preferentially in maternal tissues subject to autoimmunity, such as skin and thyroid, has also suggested the possible immune modulation of the autoimmune response at the target tissue by fetal cells. Accumulating evidence suggests that fetal immune cells may be reactive to maternal antigens and, therefore, have the capacity to trigger graft vs. host reactions. This would provide a mechanism for the initiation and/or exacerbation of autoimmune disease. The course and severity of autoimmune thyroid disease have long been known to be profoundly influenced by pregnancy, with disease suppression prepartum and exacerbation postpartum. However, the precise mechanisms involved have not been fully understood. Here we have reviewed recent information on the possible role of fetal microchimerism in autoimmune thyroid disease, focusing on the immunological consequences of intrathyroidal fetal cells and their contribution to postpartum exacerbations.     

Effects of chronic thyroid hormone administration on pregnancy, lactogenesis and lactation in the rat.

We studied the effects of daily administration of 1 mg/kg thyroxine (T4) starting 10-15 days before mating, on parturition, maternal behavior and lactation in rats. Treated rats had elevated serum titers of T3 and T4, a greater number of fetuses and parturition was advanced approximately 12 h and lasted longer than in controls. None of the treated rats were able to lactate because of defects in maternal behavior and milk ejection; the litters died usually within 48 h postpartum. In rats sacrificed at 10.00 on day 21 of pregnancy, mammary gland content of total protein, phospholipids, casein and lactose were significantly increased, but total lipid was markedly reduced. Lipogenesis was also significantly increased, as well as the activity of the lipogenic enzymes glucose-6-phosphate dehydrogenase, fatty acid synthetase and isocitrate dehydrogenase. These results are indicative of normal albeit premature lactogenesis. The T4-treated rats also had advances in the prepartum fall in serum progesterone and the increase in prolactin as well as in the increase in mammary casein and lactose concentrations of approximately 12 h with respect to control pregnant rats. These results show that chronic T4 treatment induces an advance of approximately 12 h in luteolysis, which in turn advances lactogenesis and parturition in rats. Although the mammary gland was able to produce milk, lactation failed due to abnormal maternal behavior and milk ejection, the causes of which are still unknown. Other effects of hyperthyroidism were also present, such as a severe reduction in lipid content of the gland.(ABSTRACT TRUNCATED AT 250 WORDS)     

mRNA expression profiles for corticotrophin-releasing hormone, urocortin, CRH-binding protein and CRH receptors in human term gestational tissues determined by real-time quantitative RT-PCR

Increasing maternal plasma levels of corticotrophin-releasing hormone (CRH) during the last weeks of pregnancy suggest that this stress hormone plays an important role in the control of human parturition. Little is known about the quantitative contribution of gestational tissues (other than placenta) to intrauterine formation of CRH, urocortin and CRH-binding protein (CRH-BP), or about the distribution of CRH receptors within the uterus. We have investigated the mRNA expression of CRH, urocortin, CRH-BP and CRH receptors 1 and 2 (CRH-R1 and -R2) in gestational tissues by real-time RT-PCR. Placenta, myometrium and choriodecidua were collected after uncomplicated pregnancies at term, before the onset of labour. Distribution of CRH-R1 and CRH-R2 protein was also investigated by immunostaining with receptor subtype-specific antibodies. The placenta was identified as the main site of CRH and CRH-BP mRNA expression, displaying mRNA levels >1000 and >20 times higher than those found in the myometrium and choriodecidua respectively (P<0.05 in each case). mRNA expression of urocortin was low in all tissues investigated. Myometrium and choriodecidua expressed relevant amounts of both receptor subtypes, whereas the CRH receptor population in placenta consisted mainly of CRH-R2. The high expression of CRH in placenta and the substantial expression of CRH receptors in choriodecidua and myometrium suggested that CRH derived from placenta exerts direct or indirect actions on these tissues. Neither CRH produced by myometrium or choriodecidua nor urocortin from other intrauterine sources seem to play a major role in the control of labour.     

CUSHING''S SYNDROME IN PREGNANCY: THE TIMING OF DEFINITIVE TREATMENT

Cushing's syndrome in pregnancy is rare but associated with a high fetal loss rate, premature labour and excessive maternal morbidity. There has been controversy regarding the safety and efficacy of surgical treatment during pregnancy. We describe two further cases, both due to adrenal adenomas, in whom the diagnosis was made at 28 and 31 weeks gestation. Both cases suffered from severe myopathy. The first case was not treated during pregnancy and developed wound and urinary infections after caesarean section and subsequent adrenalectomy. An incisional hernia in the caesarean section scar has been repaired twice. The second had an adrenalectomy when 29 weeks pregnant with rapid resolution of the features of Cushing's syndrome, particularly the myopathy, and had an uneventful vaginal delivery. The second case, and a review of those previously described, indicates that surgical treatment during pregnancy is safe and significantly reduces fetal losses, premature labour and maternal morbidity.     

Expression of ovarian inhibin during pregnancy in the rat

We have examined the expression of the rat inhibin genes in the maternal ovary during pregnancy. RNA blot analysis indicates that the inhibin-alpha chain mRNA is expressed in the ovary throughout gestation at levels comparable to those observed in cycling rats. In situ hybridization shows that the inhibin-alpha and -beta A mRNAs are produced in the granulosa cells of developing antral follicles; little or no hybridization to functional corpora lutea is observed. Early in pregnancy, a large number of follicles hybridize to both alpha- and beta A-inhibin cDNA probes. Many of these follicles undergo atresia during the first half of pregnancy, and the number of inhibin-expressing follicles reaches a nadir on day 15. This is followed by an increase in inhibin-producing follicles, which peaks just before parturition. The increase in inhibin-expressing follicles observed in late pregnancy corresponds to a small rise in serum inhibin levels, as measured using an alpha chain-specific RIA. After the first postpartum ovulation, few hybridizing follicles are observed. Ovariectomy in either early (day 6) or mid (day 15) pregnancy results in a significant fall in serum inhibin levels and a robust increase in serum FSH levels 9 h after surgery. These results suggest that inhibin is produced by the maternal ovary during pregnancy, that its synthesis is modulated during late gestation, and that inhibin may play a role in regulating FSH secretion during pregnancy.     

Concentrations of 6-oxo-prostaglandin F 1 alpha in the maternal and foetal plasma of sheep during spontaneous and induced parturition

The concentrations of 6-oxo-prostaglandin F 1 alpha (6-oxo-PGF 1 alpha) have been determined in maternal and foetal plasma from nine chronically catheterized sheep during late pregnancy and parturition. Labour occurred either spontaneously (three sheep) or was induced by continous intrafoetal infusion of Synacthen (ACTH 1-24; 0.24 mg/24 h; three sheep) or dexamethasone (1 mg/24 h; three sheep). During spontaneous and Synacthen-induced parturition, concentrations of 6-oxo-PGF 1 alpha in maternal and foetal plasma remained at basal levels until 24 h before delivery. At varying times during the 24 h before delivery, levels of 6-oxo-PGF 1 alpha in maternal and foetal plasma were generally increased. When parturition was induced with dexamethasone, however, no increase was observed in the foetal plasma although the concentration of 6-oxo-PGF 1 alpha in maternal plasma was raised close to delivery.     

Pregnancy and autoimmunity

Clinical immunology, already a subspecialty within internal medicine, is achieving increasing importance within the field of reproductive medicine. The recent recognition that subclinical autoimmune processes may be causally related to repeated early-pregnancy loss has allowed for the conceptional connection between the fields of infertility and obstetrics. While the immunology of infertility has been in mainstream clinical practice for years, clinical application of immunologic knowledge in obstetrics has somewhat lagged behind. The review presented here is an attempt to summarize recently recognized immune processes which affect pregnancy. Pregnancy seems particularly susceptible to immunologic interference during the very early and very late stages of gestation. During early pregnancy subclinical autoimmune processes seem capable of causing both pregnancy loss as well as congenital fetal abnormalities such as congenital heart block. Very acutely occurring immune processes in late pregnancy can endanger both maternal and fetal life and need therefore to be clinically recognized as such. The considerable progress in the clinical immunology of pregnancy made over the last few years needs to be continued by defining the clinically observed processes immunologically and biochemically in more detail. The thus obtained knowledge will not only benefit the clinical management of immunologically affected pregnancy, but will also enhance the general understanding of many far wider-reaching immunological processes. After all, pregnancy represents an unique model of nature.     

Localisation and temporal changes in prostaglandin G/H synthase-1 and -2 content in ovine intrauterine tissues in relation to glucocorticoid-induced and spontaneous labour

Parturition in the ewe is preceded by an increase in the synthesis of prostaglandins (PGs) by gestational tissues. To establish the uterine source of these PGs, placental cotyledons, fetal membranes and maternal uterine tissues were collected from ewes (n=6) at spontaneous parturition. Solubilised tissue extracts were prepared and analysed by Western blots using polyclonal antibodies to PG G/H synthase-1 and -2 (PGHS-1 and PGHS-2). PGHS-1 was expressed by all intrauterine tissues at term labour. Densitometric analysis of Western blot autoradiographs showed that the fetal membranes and maternal cervix contained the largest amounts of PGHS-1. PGHS-1 enzyme content of ovine amnion was significantly greater than that of either chorion or allantois (P<0.05). PGHS-1 protein content of myometrial, endometrial and cotyledonary tissue extracts was minimal. Formation of the PGHS-2 isozyme was confined to placental tissue at term labour. PGHS-2 protein levels in sheep placenta were significantly higher than those of PGHS-1 in all intrauterine tissues examined. This result supports the hypothesis that PGHS-2 is a major contributor to PG formation at term labour. To elucidate the developmental changes in PGHS-1 and PGHS-2 relative to labour onset, an experimental paradigm of glucocorticoid-induced delivery was used. Previous characterisation and validation of this labour model demonstrated that direct, transabdominal, intrafetal injection of the synthetic glucocorticoid betamethasone (5.7 mg in 1 ml aqueous vehicle) on day 131 of gestation induced labour onset in 56.6+/-0.8 h (mean+/-s.e.m.). As the latent period to induced-labour was known, the time course of enzyme formation could be ascertained. Sheep (n=20) were killed by barbiturate injection at various time intervals post-injection (0, 14, 28, 42 and 56 h). Tissue extracts collected at post-mortem examination were prepared and analysed by Western blots. PGHS-2 was induced in ovine cotyledon in a time-dependent fashion following glucocorticoid injection (P<0.05). There was a 12-fold increase in abundance between the time of betamethasone administration (0 h) and established labour (56 h). The PGHS-2 isozyme was not detected in any of the other tissues examined. In contrast, formation of the PGHS-1 isozyme did not change in relation to induced-labour in any of the intrauterine tissues. This finding is consistent with constitutive formation of PGHS-1. Previous studies have demonstrated a rise in PG production in association with glucocorticoid-induced labour and spontaneous delivery. The results of the present study indicate that this rise in PG production is due to increased formation of the PGHS-2 isozyme in ovine cotyledon. PGHS-2 appears to be induced by exogenous glucocorticoid administration and/or the mechanisms controlling ovine parturition. The role of PG formation by the fetal membranes is yet to be elucidated.     

Circulating levels of GH-releasing hormone and GH during human pregnancy

To study the potential role of GH-releasing hormone (GHRH) in maintaining circulating levels of GH during pregnancy, 302 maternal plasma samples were collected from non-fasted subjects at various stages of pregnancy and assayed for GHRH using a 'two-site' immunoradiometric assay. The GH and placental lactogen levels were also determined. In addition, maternal plasma samples taken during labour, amniotic fluid and cord blood were also assayed for these hormones. Maternal plasma GHRH levels were similar to non-pregnant levels throughout gestation despite fluctuations in GH values which were always higher than non-pregnant levels. There was no significant difference between GHRH levels in maternal plasma and cord blood although high GH levels were observed in the latter. These findings suggest that peripheral GHRH levels do not play an important role in maintaining circulating GH levels during pregnancy.     

Uterine expression of prostaglandin H2 synthase in late pregnancy and during parturition in prostaglandin F receptor-deficient mice

PG production in uterine tissues is important for many physiological processes in late pregnancy, including parturition. We examined the expression of the PGH2 synthases, cyclooxygenase-1 (COX-1) and COX-2, in uterine tissues during late pregnancy, using PGF receptor-deficient (FP-/-) mice. Female FP-/- mice are unable to deliver normal fetuses at term, as they do not undergo luteolysis necessary for parturition. In wild-type mice, COX-1 messenger RNA (mRNA) was expressed in the endometrial epithelium, myometrium, and decidua throughout late pregnancy. The expression of COX-1 mRNA in the endometrial epithelium and myometrium decreased both in wild-type mice undergoing natural parturition and in FP-/- mice undergoing ovariectomy-induced parturition, but expression of COX-1 mRNA was enhanced in FP-/- mice at the expected term. In wild-type mice, COX-2 mRNA was not expressed in the myometrium before parturition, but was markedly induced during parturition. This induction of COX-2 was absent in FP-/- mice at the expected term, but was found during ovariectomy-induced parturition in these mice. Expression of COX-2 proteins was confirmed by immunohistochemical analysis. Thus, in uterine tissues, myometrial expression of COX-2 is closely associated with the occurrence of parturition, but uterine expression of COX-1 is induced much earlier and kept at a high level until parturition occurs. These results suggest that COX-1-derived PGs are responsible for the induction of luteolysis, and that COX-2-derived PGs play a role in the final pathway of parturition.     

Defibrination in Normal and Abnormal Parturition

Summary Studies of blood coagulation and fibrinolysis in women undergoing uncomplicated single delivery showed a significant fall in plasma fibrinogen and factor VIII. The levels were lowest 1–4 hr postpartum and returned to pre-existing or higher levels within 24 hr. A significant fall in fibrinogen also occurred in women with twin delivery or caesarean section without labour. Similar changes were noted in factors V and VIII. Fibrinolytic activity was markedly decreased during delivery but increased rapidly thereafter in women with a single birth or caesarean section without labour. In women with twin delivery, it remained low. No consistent changes in the level of fibrinolytic inhibitors or plasminogen were noted. Mean levels of fibrinolytic degradation products (FDP) were in the upper level of the normal range and increased in the first 1–4 hr postpartum. These changes were even more marked in twin delivery. In women with abruptio placentae or prolonged intrauterine death (IUD), levels of fibrinogen, factors V and VIII and blood platelets were markedly reduced and generally dropped even lower during the first 4 hr after delivery, returning within 24 hr to the levels found in nonpregnant women. Levels of plasminogen and factor X were also reduced. High levels of FDP were found during labour, returning within 24 or 48 hr to the range observed in women 24 hr after normal delivery. Immunodiffusion and immunoelectrophoresis of serum in agar gel disclosed abnormal double or split precipitin lines. Sequential changes in these precipitin lines pointed to a continuing process which started before delivery, reached a maximum shortly thereafter, disappearing within the next 10–24 hr. The changes found in early (vs. late) labour, or during uterine surgery not associated with pregnancy, did not uphold the supposition that similar changes observed during normal or abnormal parturition might be due to the stresses of labour or surgery. The findings reported herein suggest that a minor degree of physiological defibrination develops during normal labour which is qualitatively similar to, but of much lesser magnitude than, the pathological defibrination syndrome (with local lysis of fibrin) commonly associated with abruptio placentae or prolonged intrauterine death.     

Mild gestational diabetes as a risk factor for congenital cryptorchidism

CONTEXT: Cryptorchidism is the most common malformation in newborn boys. Maternal diabetes has previously been suggested to be a risk factor for this disorder in one epidemiological study. OBJECTIVE: Evaluation of the prevalence of maternal glucose metabolism disorders during pregnancy in newborn boys having normal testicular descent or congenital cryptorchidism. DESIGN: Postnatal analysis of maternal history concerning glucose metabolism abnormalities during pregnancy among cryptorchid and healthy Finnish boys. SETTING AND PARTICIPANTS: The material of this case-control study comprises 1163 boys with normal testicular descent at birth and 125 boys with congenital cryptorchidism. All these singleton Finnish boys were born in Turku University Central Hospital (1997-2001) and were examined at birth and/or at the expected date of delivery. MAIN OUTCOME MEASURES: Information about maternal diabetes diagnosis and abnormality of the result of a 2-h 75-g oral glucose tolerance test during pregnancy were obtained from the hospital records after delivery. RESULTS: After adjustment for possible confounding factors, i.e. maternal smoking during pregnancy, maternal age at delivery, and risk factors of cryptorchidism, e.g. prematurity and weight for gestational age, abnormal maternal glucose metabolism was significantly more common in the group of cryptorchid boys [diet-treated gestational diabetes, P = 0.0001; odds ratio, 3.98 (95% confidence interval, 1.97-8.05); diet-treated gestational diabetes or only an abnormal result in oral glucose tolerance test, P = 0.0016; odds ratio, 2.44 (95% confidence interval, 1.40-4.25)] when compared with boys with normal testicular descent. CONCLUSIONS: Mildly abnormal glucose metabolism during pregnancy was associated with an increased risk for congenital cryptorchidism. The mechanism remains to be elucidated.