Francesca Monari

l-Arginine supplementation in women with chronic hypertension: impact on blood pressure and maternal and neonatal complications

Objective. To evaluate l-arginine (l-Arg) supplementation in pregnant women with chronic hypertension and its effects on blood pressure (BP) and maternal and neonatal complications. Methods. We enrolled 80 women affected by mild chronic hypertension referred to the High Risk Clinic of the Mother–Infant Department of the University of Modena and Reggio Emilia. Each woman after obtaining oral consent was randomized to receive oral l-Arg versus placebo and thereafter submitted to 24-h ambulatory BP monitoring. The primary outcome was BP change after 10–12 weeks of treatment. Secondary outcomes were as follows: percentage of women on antihypertensive treatment at delivery, maternal, and fetal outcome. Results. The BP changes after 10–12 weeks of treatment did not differ between groups. A lower percentage of women received antihypertensive drugs in the l-Arg group than the placebo group. The incidence of superimposed preeclampsia indicated delivery before the 34th weeks and certain neonatal complications tended to be higher in the placebo group. Conclusions. l-Arg supplementation in pregnant women with mild chronic hypertension does not significantly affect overall BP but is associated with less need for antihypertensive medications and a trend toward fewer maternal and neonatal complications. The results of the study were limited by the small sample size and by the exclusion of women with severe chronic hypertension. In our policy, these patients needed many hypertensive drugs and were normally managed by the cardiologist. Nevertheless, considering the promising results on maternal and fetal outcome, we believe that further studies should be performed to confirm such data and to clarify the role of l-Arg as a protective supplement in high-risk pregnancy.

Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: The PREGNANTS study

BACKGROUND: Antiphospholipid syndrome is an autoimmune, hypercoagulable state that is caused by antiphospholipid antibodies. Anticardiolipin antibodies, anti‐&bgr;2 glycoprotein‐I, and lupus anticoagulant are the main autoantibodies found in antiphospholipid syndrome. Despite the amassed body of clinical knowledge, the risk of obstetric complications that are associated with specific antibody profile has not been well‐established. OBJECTIVE: The purpose of this study was to assess the risk of obstetric complications in women with primary antiphospholipid syndrome that is associated with specific antibody profile. STUDY DESIGN: The Pregnancy In Women With Antiphospholipid Syndrome study is a multicenter, retrospective, cohort study. Diagnosis and classification of antiphospholipid syndrome were based on the 2006 International revised criteria. All women included in the study had at least 1 clinical criteria for antiphospholipid syndrome, were positive for at least 1 antiphospholipid antibody (anticardiolipin antibodies, anti‐&bgr;2 glycoprotein‐I, and/or lupus anticoagulant), and were treated with low‐dose aspirin and prophylactic low molecular weight heparin from the first trimester. Only singleton pregnancies with primary antiphospholipid syndrome were included. The primary outcome was live birth, defined as any delivery of a live infant after 22 weeks gestation. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction, and stillbirth. We planned to assess the outcomes that are associated with the various antibody profile (test result for lupus anticoagulant, anticardiolipin antibodies, and anti‐&bgr;2 glycoprotein‐I). RESULTS: There were 750 singleton pregnancies with primary antiphospholipid syndrome in the study cohort: 54 (7.2%) were positive for lupus anticoagulant only; 458 (61.0%) were positive for anticardiolipin antibodies only; 128 (17.1%) were positive for anti‐&bgr;2 glycoprotein‐I only; 90 (12.0%) were double positive and lupus anticoagulant negative, and 20 (2.7%) were triple positive. The incidence of live birth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared with women with only 1 antibody positive test results, women with multiple antibody positive results had a significantly lower live birth rate (40.9% vs 56.6%; adjusted odds ratio, 0.71; 95% confidence interval, 0.51–0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; adjusted odds ratio, 1.56; 95% confidence interval, 1.22–1.95) and with severe features (22.7% vs 13.8%, adjusted odds ratio, 1.66; 95% confidence interval, 1.19–2.49), of intrauterine growth restriction (53.6% vs 40.8%; adjusted odds ratio, 2.31; 95% confidence interval, 1.17–2.61) and of stillbirth (36.4% vs 21.7%; adjusted odds ratio, 2.67; 95% confidence interval, 1.22–2.94). In women with only 1 positive test result, women with anti‐&bgr;2 glycoprotein‐I positivity present alone had a significantly lower live birth rate (47.7% vs 56.3% vs 79.6%; P<.01) and a significantly higher incidence of preeclampsia without (47.7% vs 34.1% vs 11.1%; P<.01) and with severe features (17.2% vs 14.4% vs 0%; P=.02), intrauterine growth restriction (48.4% vs 40.1% vs 25.9%; P<.01), and stillbirth (29.7% vs 21.2% vs 7.4%; P<.01) compared with women with anticardiolipin antibodies and with women with lupus anticoagulant present alone, respectively. In the group of women with >1 antibody positivity, triple‐positive women had a lower live birth rate (30% vs 43.3%; adjusted odds ratio,0.69; 95% confidence interval, 0.22–0.91) and a higher incidence of intrauterine growth restriction (70.0% vs 50.0%; adjusted odds ratio,2.40; 95% confidence interval, 1.15–2.99) compared with double positive and lupus anticoagulant negative women. CONCLUSION: In singleton pregnancies with primary antiphospholipid syndrome, anticardiolipin antibody is the most common sole antiphospholipid antibody present, but anti‐&bgr;2 glycoprotein‐I is the one associated with the lowest live birth rate and highest incidence of preeclampsia, intrauterine growth restriction, and stillbirth, compared with the presence of anticardiolipin antibodies or lupus anticoagulant alone. Women with primary antiphospholipid syndrome have an increased risk of obstetric complications and lower live birth rate when <1 antiphospholipid antibody is present. Despite therapy with low‐dose aspirin and prophylactic low molecular weight heparin, the chance of a liveborn neonate is only 30% for triple‐positive women.

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.

Fetal bacterial infections in antepartum stillbirth: A case series

OBJECTIVES This study aims to assess the frequency of fetal bacterial infections in stillbirth (SB) and to evaluate the best samples for the diagnosis of infection-related SB. STUDY DESIGN Consecutive cases of antepartum SB were enrolled. Vaginal and placental swabs, as well as heart blood cultures and surface swabs from the neonate, were collected. Histological examinations were performed by the same examiner. Immunohistochemistry for leukocyte common antigen was performed in the placenta and fetus. Each case was discussed in a multidisciplinary audit. RESULTS One hundred and nine cases were enrolled. Fetal blood cultures were positive in 20/95 cases (21%). Significant histological findings in the placenta/cord and in at least one fetal organ were observed in 8 cases of them (4 Group B Streptococcus GBS, 2 Listeria monocytogenes, 1 Coagulase negative Staphylococcus, 1 Pseudomonas aeruginosa). Neither tissue damage nor inflammatory infiltrate was found in the 12 remnant cases. Funisitis while not histological chorioamnionitis was associated with microbiological findings. Positive findings in maternal/placental/fetal swabs occurred in 18-32% of cases with both negative fetal blood cultures and histopathological findings. With the exception of GBS, no other bacteria agent could be detected by any of the swabs. CONCLUSIONS Eight cases (8.4%) fulfilled both microbiological and histology criteria allowing the diagnosis of SB-related fetal infection demonstrating that search for infections is essential in SB evaluation. Fetal blood culture, placenta swab for GBS and search for histological funisitis are mandatory actions within the SB work-up in order to guide pathology examination and reach clinical conclusions.

Management of subsequent pregnancy after antepartum stillbirth. A review.

In literature, there is a paucity of information about the management of the subsequent pregnancy after stillbirth (SB). we undertook a systematic review of the literature focusing on the evidence for antenatal interventions with the potential to prevent SB and we try to summarise the management of the pregnancy subsequent to a SB. The diverse interventions and their efficacy will be reported according to the possible causes and/or conditions associated to the previous SB. Few of the studies reported SB as an outcome and the evidence was frequently conflicting. Several interventions showed clear evidence of impact on SB, including the scrupulous control of blood sugar by using multiple doses of insulin, frequent antenatal foetal monitoring and timing of delivery in diabetic women; the prophylaxis with low dose of aspirin in high-risk women; or serial sonograms for foetal growth, Doppler studies and antepartum foetal testing in women with previous growth restricted foetus. Other interventions instead reduced know risk factors for SB but failed to show statistically significant impact on SB rate. Overall, early access to care, at least three ultrasounds examinations, screening for the main pregnancy-related disorders and timely delivery are the milestone of appropriate antenatal care in women with previous SB.

Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders

Objective To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders. Study Design A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was “adverse neonatal outcome”, including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxic-ischemic encephalopathy, intracranial hemorrhage or respiratory distress. Results Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2–3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1–4.3). Conclusion When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor.

Acupuncture in post-date pregnancy: a pilot study

Abstract Aim: Pharmacological labor induction is obtained through intracervical/vaginal prostaglandins and/or oxytocin infusion; however, the use of these agents produces fetal and maternal side effects. Traditional Chinese medicine advocates the use of acupuncture to soften the cervix and induce uterine contractions. The aim of the present study is to investigate the effect of acupuncture to induce labor. Acupuncture was applied in post-date pregnancies one week before a planned induction; the primary outcome was the rate of women submitted to labor induction for prolonged pregnancy at week 41 + 5. Methods: After informed consent, 221 undelivered women ranging between 40 + 2/40 + 6 gestational age were considered eligible for the study and 202 were randomized to receive acupuncture or observation. Sessions of acupuncture were planned every odd day from the randomization till 41a week plus 4 days. At 41 + 5 week a pharmacological induction of labor was planned. Results: The total rate of labor induction did not significantly differ between observation and acupuncture group (20% versus 17%). Moreover no differences were found as far as the indications to induce labor, in particular “prolonged pregnancy” was similar between groups (8/96 versus 5/99). To investigate between-group differences in time elapsed between inclusion and delivery, survival analysis was performed excluding women requiring labor induction: women receiving acupuncture showed a trend to deliver earlier than women in the observation group (p < 0.09). Conclusion: The present study demonstrated that acupuncture applied every odd day for one week seems ineffective in reducing the rate of labor induction performed for prolonged pregnancy at 41 + 5 weeks. Previous reports reached similar conclusions, independently of the different timing, duration and mode of stimuli application.

Effect of maternal age, height, BMI and ethnicity on birth weight: An Italian multicenter study

Abstract Aim: To assess the effect of maternal age, height, early pregnancy body mass index (BMI) and ethnicity on birth weight. Subjects and methods: A cross-sectional study was conducted on more than 42,000 newborns. Ethnicity was defined by maternal country of birth or, when missing (<0.6% of records), by citizenship. The effect of maternal characteristics on birth weight was evaluated with general linear models. Results: Maternal height and BMI, although not age, significantly affected birth weight. Among Italian babies, 4.7% of newborns were classified as appropriate-for-gestational age (AGA) (birth weight between the 10th and the 90th centile) according to the country-specific Italian Neonatal Study (INeS) charts and were re-classified as either large-(LGA) (birth weight >90th centile) or small-(SGA) (birth weight <10th centile) for gestational age (GA) after adjustment for maternal characteristics. On the contrary, 1.6% of Italian newborns were classified as SGA or LGA according to the INeS charts and re-classified as AGA after adjustment. Maternal ethnicity had a significant impact on birth weight. Specifically, babies born to Senegalese mothers were the lightest, whilst babies born to Chinese mothers were the heaviest. Conclusions: Maternal height and early pregnancy BMI, should be considered in the evaluation of birth weight. The effect of ethnicity suggests the appropriateness of ethnic-specific charts. Further studies are necessary to determine if changes in birth weight classification, may translate into improved detection of subjects at risk of adverse outcomes.