Serial cervical-length measurements after first episode of threatened preterm labor improve prediction of spontaneous delivery prior to 37 weeks' gestation.

OBJECTIVE: To assess whether repeat cervical-length (CL) measurement in women discharged from hospital after their first episode of threatened preterm labor can predict their risk of spontaneous preterm birth. METHODS: This was a secondary analysis of a randomized controlled trial of maintenance tocolysis, in which CL was measured on transvaginal ultrasound at the time of hospital discharge and after 2, 4, 8 and 12 weeks, in women who remained undelivered after their first episode of threatened preterm labor. After univariate analysis, multivariate logistic regression analysis was used to assess whether CL < 10 mm at the time of hospital discharge or at any follow-up evaluation could predict spontaneous delivery prior to 37 weeks of gestation. RESULTS: Of 226 women discharged after a diagnosis of threatened preterm labor, 57 (25.2%) delivered spontaneously prior to 37 weeks' gestation. The risk of spontaneous preterm birth was higher among women with CL < 10 mm at hospital discharge compared to those with CL ≥ 10 mm (adjusted odds ratio (aOR), 3.3; 95% CI, 1.2-9.2). Moreover, spontaneous preterm delivery was more common when CL < 10 mm was detected up to 2 weeks (aOR, 2.9; 95% CI, 1.1-7.3) or up to 4 weeks (aOR, 7.3; 95% CI, 2.3-22.8) post discharge, as compared with when CL was persistently ≥ 10 mm. The association was not significant when considering CL measurements at 8 weeks, and there was insufficient information to assess the effect of measurements obtained at 12 weeks. CONCLUSIONS: Women who remain undelivered after their first episode of threatened preterm labor continue to be at high risk of spontaneous preterm birth if their CL is below 10 mm at the time of hospital discharge or at any follow-up visit up to 4 weeks later. CL measurement could be included in the antenatal care of these women in order to stratify their risk of preterm birth, rationalize resource utilization and help clinicians improve pregnancy outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Genetic background and risk of postpartum haemorrhage: results from an Italian cohort of 3219 women.

Postpartum haemorrhage (PPH) is a leading cause of maternal mortality, particularly in the developing countries, and of severe maternal morbidity worldwide. To investigate the impact of genetic influences on postpartum haemorrhage, in association with maternal and intrapartum risk factors, using a candidate gene approach. All women (n = 6694) who underwent a vaginal delivery at the Obstetric Unit of a large University hospital in Milan (Italy) between July 2007 and September 2009 were enrolled. The first consecutive 3219 women entered the genetic study. Postpartum haemorrhage was defined as ≥500 mL blood loss. Eight functional polymorphisms in seven candidate genes were chosen because of their potential role in predisposing to or protecting from haemorrhagic conditions: tissue factor (F3), factor V (F5), tissue factor pathway inhibitor (TFPI), platelet glycoprotein Ia/IIa (ITGA2), prothrombin (F2), platelet glycoproteins Ibα (GP1BA) and angiotensin-converting enzyme (ACE). After correction for the already known PPH risk factors, only the promoter polymorphism of the tissue factor gene (F3 -603A>G) showed a significant association with PPH, the G allele exerting a protective effect (P = 0.00053; OR = 0.79, 95% CI = 0.69-0.90). The protective effect against PPH of the TF -603A>G polymorphism is biologically plausible since the G allele is associated with an increased protein expression and Tissue Factor is strongly represented in the placenta at term, particularly in decidual cells of maternal origin.

Obstetric and vascular APS: same autoantibodies but different diseases?

Beta2 glycoprotein I (ß2GPI)-dependent antiphospholipid antibodies (aPLs) are the main pathogenic autoantibody population and at the same time the laboratory diagnostic tool for the antiphospholipid syndrome (APS). These antibodies are responsible for both the vascular and the obstetric manifestations of the syndrome but the pathogenic mechanisms behind these manifestations are not the same. For example, thrombotic events do not appear to play a major role in APS miscarriages and a direct reactivity of ß2GPI-dependent aPLs on decidual and trophoblast cells was reported. A local expression of ß2GPI on these tissues was reported both in physiological conditions and in APS women, thus explaining the local tropism of the autoantibodies. The two hit hypothesis was suggested to explain why the vascular manifestations of APS may occur only occasionally in spite of the persistent presence of aPLs. This is not apparently the case for the obstetric variant of the syndrome, making the difference even more striking. A different pathogenesis may also provide the rationale for the well-known fact that the vascular and the obstetric manifestations may occur independently although in a minority of cases.

[Does chorioamnionitis worsen the outcome of preterm infants? A controversial issue]. / La corioamnionite peggiora l'outcome del neonato prematuro? Una questione controversa.

The term chorioamnionitis is used to describe an intrauterine status of infection/inflammation of either mixed fetal-maternal (choriodecidual space) or fetal origin (chorioamniotic membranes, amniotic fluid, umbilical cord). Histological, microbiological, biochemical and clinical criteria are used to define chorioamnionitis. Histopathological examination of the placenta is the gold standard for evaluating antenatal inflammatory processes that might influence fetal development. Chorioamnionitis is the leading cause of very preterm delivery and its incidence increases with decreasing gestational age. Therefore, it contributes to the high morbidity and mortality of infants born prematurely. In the last decades, several studies have been performed to assess a gestation-independent effect of chorioamnionitis on neonatal and long-term outcome with variable results. The discrepancy observed across studies may be attributable to differences in inclusion and exclusion criteria, disease definitions, methods, and whether potential confounding factors such as gestational age were considered. As underlined by several Authors, the increasingly widespread use of antenatal steroids may have contributed to improve neonatal outcome and can therefore partially explain the different results between studies. In the current review we aim to give an overview and synthesis of a vast amount of existing literature on the association between antenatal infection/inflammation and neonatal and long-term outcome.

Anti-phospholipid antibody mediated fetal loss: still an open question from a pathogenic point of view.

Antiphospholipid antibodies (aPL) are associated with recurrent miscarriages and pregnancy complications, however their pathogenic mechanisms are still matter of research. Thrombotic events at the placental level cannot explain all of the clinical manifestations. It has been suggested that aPL may be responsible for a local acute inflammatory response mediated by complement activation and neutrophil infiltration eventually leading to fetal loss. However histological and immunohistological studies on human placental samples do support such a mechanism only in part and with no any clear relationship with the pregnancy outcome. A direct effect of aPL on both maternal and fetal placental tissues has been reported through the reactivity of the antibodies with beta2 glycoprotein I (beta2GPI) expressed on the cell membranes. These events do not require an inflammatory response and can be in part related to the inhibition of growth factors favouring a physiological placentation. Understanding the different pathogenic mechanisms of aPL-associated miscarriages may help in improving our therapeutic approach particularly in recurrent cases not responsive to the usual treatment.

Monitoring and treatment of anti-D in pregnancy.

Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe.

Pregnancy complications of the antiphospholipid syndrome.

Starting from their first description, antiphospholipid antibodies (aPL) were associated with repeated miscarriages and fetal losses. Other complications of pregnancy like preterm birth,with pre-eclampsia or severe placental insufficiency were also frequently reported and are included in the current classification criteria of the antiphospholipid syndrome (APS). The titre, the isotype of the antibodies or their antigen specificity may be important in the risk level determination. Some of the difference in the reported results can be explained by the poor standardization achieved in aPL testing or by the not univocal classification of pregnancy complications. The pathogenesis of pregnancy failures is linked to the thrombophilic effect of aPL but also to different mechanisms including a direct effect of antibodies on the throphoblast differentiation and invasion. The study of experimental animal models provided sound evidence of the pathogenic role of aPL both in lupus prone and naive mice. The definition of APS as a condition linked to high obstetric risk and the application of an effective therapy have completely changed the prognosis of pregnancy in these patients. In fact, despite the high number of complications and preterm delivery, today a successful outcome can be achieved in the large majority of the cases.

Risk factors for spontaneous abortion.

A case-control study was conducted to evaluate risk factors for spontaneous abortions. Cases were 94 women with two or more unexplained miscarriages (after exclusion of genetic, endocrine and Müllerian factors) and no term pregnancy, controls were 176 women admitted for normal delivery to the same clinic where cases were identified. Questions were asked about personal characteristics and habits, and gynaecological history. A family history of recurrent miscarriage was more common among women with spontaneous miscarriages than among the controls (13 cases versus 8 controls, relative risk (RR) = 3.2, 95% confidence interval (CI) = 1.3-8.1). Compared to women whose menarche occurred at age 11 or younger, the RRs were 0.8 when menarche occurred at age 12-13 and 0.5 at age 14 or more: this trend in risk was statistically significant. Compared with never smokers, current smokers had about a 40% increased risk of miscarriage and the risk increased with number of cigarettes per day. No association emerged with sociodemographic characteristics (e.g. education, marital status, age of the partner), reproductive history (age at first pregnancy), type of contraceptive used and other general lifestyle habits (e.g. alcohol or coffee consumption).

Ectopic pregnancy and recurrent spontaneous abortion: two associated reproductive failures.

The association between spontaneous abortion and ectopic pregnancy was evaluated in a case-control study conducted on 161 women (cases) with recurrent spontaneous abortions (two or more consecutive spontaneous abortions) and 170 control subjects who delivered normal infants. The risk of ectopic pregnancy in women with a history of recurrent spontaneous abortion was about fourfold that of controls (relative risk adjusted for age and number of pregnancies = 4.3; 95% confidence interval 1.4-14.7). This association was confirmed by comparing the observed number of extrauterine pregnancies in women with recurrent spontaneous abortions with the expected number computed from regional data on the frequency of ectopic pregnancies; the estimated relative risk was 3.7, with a 95% confidence interval of 2.2-7.0. The present report found an association between spontaneous abortions and ectopic pregnancies, suggesting some common risk/etiologic factors for these two reproductive failures.

Antiphospholipid antibodies and recurrent abortion.

We examined the association between anticardiolipin antibodies, lupus anticoagulant, and the risk of recurrent spontaneous abortion in a case-control study conducted in a network of general and teaching hospitals in northern Italy. Subjects consisted of 220 women with two or more unexplained consecutive spontaneous abortions and 193 controls admitted for acute conditions other than immunologic, infective, gynecologic, or cardiovascular. Lupus anticoagulant was detected in 16 of 220 cases (7%, 95% confidence interval 4-11%) but in none of the 193 controls (Fisher exact test, P less than .001). Increased anticardiolipin antibody levels were demonstrated in 19 of 99 cases (19%, 95% confidence interval 12-31%) (seven immunoglobulin (Ig) G, eight IgM, and four IgG and IgM) and in four (all IgG) of 157 controls (3%) for whom data were available. These results offer quantitative evidence on the association between antiphospholipid antibodies and recurrent abortion.

Recovery of Chlamydia trachomatis from the endometria of women with unexplained infertility.

Fifty-two women with unexplained infertility and 55 controls with recently proved fertility were screened for Chlamydia trachomatis (CT) infection in the blood and genital tract. Serum antibody titration was performed with indirect fluorescence. Cell cultures were performed to screen for CT in urethral and endocervical swabs, in endometrial samples taken without endocervical contamination and in salpingeal and/or peritoneal fluid samples. Anti-CT serum antibodies were detected in 36.5% of the patients; CT was isolated in urethral cultures in 26.9%, endocervical cultures in 23.1%, endometrial cultures in 25% and endosalpingeal and/or peritoneal fluid cultures in 1.9%. Comparison of the results in the patients and controls showed a significant difference in the incidence of CT infection in endometrial, urethral and endocervical cultures. Chlamydial endometritis could have been the direct cause of infertility in the patients studied or merely might have indicated endosalpingitis that was not detectable at laparoscopy.

Electrocardiographic abnormalities in infants born from mothers with autoimmune diseases--a multicentre prospective study.

OBJECTIVES: To assess the prevalence of congenital heart block (CHB) and electrocardiographic (ECG) abnormalities in infants of anti-Ro/SSA-positive women. METHODS: Sixty anti-Ro-positive and 36 anti-Ro-negative patients were prospectively followed before/during pregnancy and underwent weekly fetal echocardiography from 18th to 26th weeks of gestational age. Infants' ECG and/or ECG-Holter were performed at 1, 3, 6 and 12 months. ECG of 200 consecutive neonates were used as a healthy control group. RESULTS: One of 61 fetuses of anti-Ro-positive mothers developed CHB (20th week); another anti-Ro-positive baby developed second degree atrioventricular (AV) block (30th week). The prevalence of transient first degree AV block detected post-natally was significantly higher in the anti-Ro-positive group, in comparison with healthy controls (P = 0.002). No differences in corrected QT (QTc) interval prolongation prevalence (>/=440 ms) was observed between the anti-Ro-positive and -negative groups, but both were significantly higher than that of the control population (P < 0.001). ECG-Holter showed QTc prolongation in 59% of infants of anti-Ro-positive and in 60% of infants of anti-Ro-negative mothers. Holter QTc was >/=470 ms in four infants of anti-Ro-positive group and two of anti-Ro-negative group. Known acquired causes of QTc prolongation were excluded. CONCLUSIONS: This prospective study confirms the low occurrence of CHB in newborns from anti-Ro-positive mothers. ECG abnormalities (first degree AV block and QTc interval prolongation) are frequent in infants of mothers with autoimmune diseases, independently of maternal disease, autoantibody profile and treatment during pregnancy.

Increased frequency of complete hydatidiform mole in women with repeated abortion.

The association between spontaneous abortion and gestational trophoblastic disease (GTD) has been investigated in a study based on 93 women with 2 consecutive (repeated) spontaneous abortions and 82 control subjects who delivered normal babies. Nine molar pregnancies were observed among 7 of the 93 cases of repeated abortion while no control reported previous GTD. This difference was statistically significant and was not explained by allowance for age and number of pregnancies between cases and controls (chi 2(1) = 4.20; P = 0.04). When the observed number (9) of hydatidiform mole in the 385 pregnancies of the women with repeated abortion was compared with the expected one (0.28) based on the regional frequency data, the estimated relative risk was 32.1 with a 95% confidence interval from 13.9 to 63.3. The present findings confirm the association between GTD and spontaneous abortion and indicate that the risk is larger in women with repeated abortions.

Short-term reproductive prognosis when no cause can be found for recurrent miscarriage.

The short-term reproductive prognosis of recurrent miscarriage for which no cause was found has been evaluated in 95 couples investigated between 1980 and 1986 at the First Obstetric and Gynaecological Clinic of the University of Milan. The actuarial overall 3-year livebirth delivery rate was 64%, increasing constantly with time. The reproductive success rate decreased with the number of previous miscarriages from 80% in women with two, to 60% with three and 46% with four or more miscarriages. No effect of age and socio-economic status emerged. There was a positive association between the number of previous miscarriages and the risk of miscarriage in the next pregnancy. Compared with women with two miscarriages the relative risk of another miscarriage was 2.3 for those with three previous miscarriages and 5.0 for those with four or more (chi 2 1 for trend adjusted for age = 5.2, P = 0.02).

Varying clinical course of large placental chorioangiomas. Report of 3 cases.

Three cases of placental chorioangiomas, from 6.5 to 10 cm in diameter, were diagnosed prenatally by ultrasound and color Doppler imaging at 21-34 weeks of gestation. In 1 case, due to fetal hydrops and maternal 'mirror syndrome', immediate delivery of a neonate, who was severely anemic, thrombocytopenic and had consumption coagulopathy, was required. In the other 2 pregnancies, conservative management was possible, once fetal cardiac failure and anemia were ruled out by the combination of fetal blood sampling and serial echographic and Doppler investigations.