Paolo Venturini

Maternal thrombophilia and the risk of recurrence of preeclampsia

OBJECTIVE The aim of this prospective study was to determine the impact of thrombophilia on the recurrence of preeclampsia. STUDY DESIGN In a multicenter, observational, cohort design, 172 white patients with a previous pregnancy complicated by preeclampsia were observed in the next pregnancy. They were evaluated for heritable thrombophilia (factor V Leiden and factor II G20210A mutations, protein S, protein C, and antithrombin deficiency), hyperhomocystinemia, lupus anticoagulant, and anticardiolipin antibodies. Development of preeclampsia and maternal complications and both gestational age at delivery and birthweight were recorded. RESULTS Sixty women (34.9%) showed the presence of a thrombophilic defect. They had a higher risk for the recurrence of preeclampsia (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.2-5.1), compared to patients without thrombophilia. Similar findings were observed considering only heritable thrombophilia. Thrombophilic patients were at increased risk for the occurrence of very early preterm delivery (< 32 weeks; OR, 11.6; 95% CI, 3.4-43.2). CONCLUSION When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management.

17α-Hydroxy-Progesterone Effects on Cervical Proinflammatory Agents in Women at Risk for Preterm Delivery

We evaluated if the inhibitory effect of 17alpha-hydroxyprogesterone caproate (17P) on cervical ripening is mediated by cervical proinflammatory agents. Women with singleton pregnancy and intact membranes, between 25 and 33 weeks + 6 days, were randomly allocated either to observation (22 cases, controls) or to receive 341 mg of intramuscular 17P (23 cases, 17P group), twice a week, until 36 weeks. Just before randomization, 7 and 21 days later, a cervical swab for interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and nitrates/nitrites (NOx) assays was collected. Moreover, an ultrasound measure of cervical length (CL) was performed at the same time. At randomization, both groups of women showed similar levels of cervical ILs and NOx. In the 17P group, cervical IL-1beta levels were significantly decreased at day 21 ( P = 0.036); in controls, they remained stable throughout the observation period. There was no significant change in IL-6, IL-8, TNF-alpha, and NOx in either group. Women in the control group had a progressive CL shortening until day 21 (median shortening of 4 mm), and this shortening was significantly less in the 17P group (median shortening of 2 mm; P = 0.017). In patients at risk of preterm labor, high-dose 17P simultaneously inhibits both cervical proinflammatory IL-1beta secretion and the progressive shortening of the cervix.

Changes in the cervical competence in preterm labour

Cervical competence is a key function in normal and abnormal labour. Remodelling of the cervical structure, by reorientation and changes in the integrity of collagen fibres by an alteration in the content of water, proteoglycans and hyaluronic acid, takes place before parturition. Such morphological changes have been associated with the activation of several biochemical pathways, sharing those of an apyretic, proinflammatory reaction, including the inducible isoform of the nitric oxide synthase (NOS). Nitric oxide (NO) is believed to be the final mediator in the mechanisms that allow ripening of the cervix. A reduction of NO activity in the uterus, together with its activation in the cervix, is hypothesised to be a facilitating factor in human parturition. The local application of NO donors in both animals and humans induces ultrastructural changes similar to those occurring during physiological cervical maturation. NO donors have proven to be clinically effective in facilitating first trimester dilation and curettage. Preliminary data also suggest that in women presenting with threatening preterm labour, there is increased activity of NO in the cervix, which is associated with shortening. A complex interaction between cytokines, prostaglandins (PGs) and NO is the key biochemical pathway accounting for the preterm ripening of the cervix.

Effects of three different stimulations (acupuncture, moxibustion, acupuncture plus moxibustion) of BL.67 acupoint at small toe on fetal behavior of breech presentation.

The aim of the study was to evaluate cardiovascular effects and fetal behavior during moxibustion, acupuncture or acupuncture plus moxibustion applied on the BL.67 acupoint of women (beside the outer corner of the 5th toenail) in fetal breech presentation. During the acupoint stimulation (20 min, two times a week), the women were submitted to computerized non-stress test. Fourteen cases were treated by both acupuncture and moxibustion, 15 cases by moxibustion and 10 cases by acupuncture. In 56% of cases, fetal position was converted from breech position to cephalic one; the success share was 80% for moxibustion, 28% for acupuncture, 57% for acupuncture plus moxibustion; the conversion, on average, was achieved after 3 sessions. Statistical analysis indicated that acupuncture plus moxibustion was able to reduce fetal heart rate during the application of stimuli while acupuncture and moxibustion separately did not affect such parameter. Moreover, moxibustion and acupuncture with moxibustion reduced fetal movements while acupuncture only appears ineffective. The present study suggests that fetal movements were reduced by both acupuncture plus moxibustion and moxibustion and that fetal heart rate was reduced just by acupuncture plus moxibustion. The mechanisms leading the effect on fetal heart rate and fetal movements remain to be clarified. Even though further studies are needed, such preliminar report mainly investigated the impact of different stimula on the BL.67 acupoint. Unfortunately these small series of data do not allow us to draw any conclusion about the effectiveness of the different treatments.

Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death

OBJECTIVE To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death. STUDY DESIGN In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed. RESULTS Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95% CI: 1.3-13.5). CONCLUSION These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia.

Induction of labor in women with oligohydramnios

OBJECTIVE To prospectively evaluate the outcome of labor induction in women with oligohydramnios at term. METHODS This was a prospective case-control study which included 120 consecutive patients with Amniotic Fluid Index (AFI) < or =5 undergoing labor induction. One hundred and sixteen patients with normal amniotic fluid matched for gestational age (+/- 3 days) and Bishop-score served as controls. Inclusion criteria were: requirement of labor induction, singleton pregnancy, nulliparity, Bishop score <5, gestational age > or =266. Preinduction treatment included the use of up to 3 successive doses of dinoprostone intracervical gel (0.5 mg). Vaginal dinoprostone (2 mg) and/or oxytocin were then applied to induction labor, if necessary. RESULTS The rate of cesarean section in AFI < or = 5 group (38.3%) was not significantly different to that in control group (34.2%). The interval from induction to vaginal delivery was not significantly different for AFI < or =5 group (1499 +/- 895 min.) and control group (1398 +/- 852 min.). The changes in Bishop score evaluated at 6th and 12th hour after dinoprostone were not significantly different in control and AFI< or =5 group. More women in the latter group (11.7% vs 3.3%, Chi Square:4.86, p = 0.027) required the use of drugs in order to manage tachysystole/hyperstimulation allowing a OR = 3.83 (95%C.I. = 1.13-14.27). The length of stay at hospital was 4.2 +/- 1.8 days for AFI < or =5 group and 4.3 +/- 1.3 for control group. CONCLUSIONS Oligohydranmios at term did not influence the outcome of induction of labour in nulliparous women with unfavorable cervix.