Apheresis treatment of cryoglobulinemic vasculitis: A multicentre cohort study of 159 patients.

OBJECTIVE: To assess the effectiveness of apheresis therapy (AT) in treating the clinical manifestations of patients with complicated cryoglobulinemic vasculitis (CV). METHODS: A retrospective cohort study of 159 CV patients attending 22 Italian Centers who underwent at least one AT session between 2005 and 2015. The response to AT was evaluated on the basis of a defined grading system. RESULTS: Peripheral neuropathy was the most frequent clinical condition leading to AT. Therapeutic plasma exchange was used in 70.4% of cases. The outcome of AT was rated very good in 19 cases, good in 64, partial/transient in 40, and absent/not assessable in 36. Life-threatening CV-related emergencies and renal impairment independently correlated with failure to respond to AT. The independent variables associated with an increased risk of death were age at the time of the first AT session, multi-organ life-threatening CV, the presence of renal impairment and failure to respond to AT. The time-dependent probability of surviving until CV-related death in the second year was 84%, with an AHR in patients with absent/not assessable response to AT of 11.25. CONCLUSION: In this study AT is confirmed to be a safe procedure in patients with CV. Early AT should be considered in patients with severe CV, especially in cases with impending renal involvement, in order to prevent irreversible kidney damage. Although its efficacy in patients with multi-organ failure is limited, AT is the only treatment that can rapidly remove circulating cryoglobulins, and should be considered an emergency treatment.

Bone mineral changes during and after lactation.

OBJECTIVE: To investigate variations in bone mineral density during lactation and throughout the 12 months after scheduled cessation of lactation in relation to the resumption of ovarian function. METHODS: Three hundred eight mothers who decided to lactate were scheduled to fully breast-feed for 6 months, followed by a 1-month weaning period, and then suppress lactation with cabergoline. Their bone mineral density variations were compared with those of a control group of nonlactating mothers during the first 18 months postpartum. Half the lactating women were given daily oral calcium supplements of 1 g in an open design. RESULTS: There was a significant progressive decrease in bone mineral density in lactating women over the first 6 months, followed by recovery of bone mass up to levels that at 18 months were higher than baseline. In nonlactating women, bone mineral density increased progressively after delivery, and at 18 months postpartum had increased by 1.1-1.9% compared with baseline. Compared with lactating women who resumed menstruation within 5 months of delivery, breast-feeding mothers with longer amenorrhea initially lost more bone, but they also gained significantly more bone after resumption of menses, so there were no differences at 18 months postpartum. Oral calcium supplementation decreased bone loss, but had only a transient effect. CONCLUSION: A scheduled lactation period of 6 months, followed by a 1-month weaning period, allowed bone mineral density to reach higher values compared with early postpartum, regardless of calcium supplementation and duration of postpartum amenorrhea.

Torulopsis glabrata vaginitis.

OBJECTIVE: To study the sociodemographic risk factors and clinical features of Torulopsis glabrata vaginal infection. METHODS: We evaluated the sociodemographic and clinical characteristics of 86 consecutive symptomatic women attending a vaginitis clinic and isolated T glabrata. Case patients were compared with a control group of 174 asymptomatic women with negative vaginal cultures and an additional group of 625 symptomatic women with vaginal cultures positive for Candida albicans. In addition, the sensitivity of the isolates to the more common antimycotic agents used was tested by the modified Kirby-Bauer method. RESULTS: Patients with T glabrata vaginal infection were from lower socioeconomic backgrounds and had less education. They were more likely to use vaginal tampons and to be seropositive for human immunodeficiency virus than were negative controls. Compared with C albicans infection, T glabrata was more frequent among women over 38 years of age and in those with less education and of lower social class. In logistic regression analysis, T glabrata was associated more frequently with recurrent vaginal candidiasis than was C albicans (odds ratio 2.46, 95% confidence interval 1.33-4.54; P = .004). Six of the 86 (7%) T glabrata isolates and none of the C albicans isolates (P < .001 by Fisher exact test) were resistant to the imidazole derivatives tested. CONCLUSION: Torulopsis glabrata was isolated in 10% of women with vulvovaginal candidiasis attending a vaginitis clinic. This infection was associated with recurrent vaginitis in almost one-third of case patients presenting with symptoms.

Meconium-stained amniotic fluid and risk for cerebral palsy in preterm infants.

OBJECTIVE: To estimate the risk for cerebral palsy in preterm infants in relation to the presence of meconium in the amniotic fluid (AF). METHODS: A cohort study was conducted of 404 consecutive preterm infants delivered between 24 and 33 weeks' gestation at a single institution. Sociodemographic and clinical data were collected at birth. The diagnosis of cerebral palsy was made at 2 years' corrected age. Politomous logistic regression models were used to evaluate the odds for cerebral palsy while adjusting for potential confounders. RESULTS: The overall prevalence of cerebral palsy among survivors was 11.6% (40/345). The cerebral palsy rate was 41.2% (7/17) among infants who were meconium-stained at birth and 10% (33/328) among those who were not (P = .006 by Fisher exact test). After adjustment for potential confounders (gestational age and fetal gender), the odds ratio of cerebral palsy among infants delivered to women with meconium-stained AF was 6.9 (95% confidence interval 2.32, 20.81, P = .001) relative to those delivered to women with clear AF. CONCLUSION: The results of the present study support the view that the presence of meconium in the AF is a gestational age-independent risk factor for cerebral palsy among preterm infants.

Case-control study of maternal blood group and severe pre-eclampsia.

The relation of maternal blood group to pre-eclampsia has not been adequately studied in previous research. To investigate this relation, we conducted a case-control study of primigravidae. Data on 204 consecutive severely pre-eclamptic patients delivered pre-term and 744 controls were analysed using multivariate methods. After adjustment for the confounding effects of maternal age, social class, origin, education, pre-pregnancy weight and body mass index, and weight gain in pregnancy, we found an increased risk of pre-eclampsia for mothers with blood type AB (adjusted odds ratio = 3.07; 95% confidence interval 1.48-6.36). With respect to blood group O, A, B and Rh type, no statistically significant correlation with severe pre-eclampsia was found. Although these results should be considered with caution, they support the hypothesis of a linkage mechanism involving blood group in the inheritance of susceptibility to pre-eclampsia.

Cigarette smoking in pregnancy and risk of pre-eclampsia.

The relationship between smoking in pregnancy and the development of pre-eclampsia has not been well studied. Smoking habits were prospectively evaluated in 117 patients with pre-eclampsia and 468 normotensive control pregnancies. Twenty cases (17.1%) and 120 controls (25.6%) reported smoking at any time during pregnancy. In stepwise multiple logistic regression analysis, smoking in pregnancy was a significant protective factor against the occurrence of pre-eclampsia (adjusted odds ratio = 0.50; 95% confidence interval 0.28-0.80, P = 0.018). On the other hand, a history of pre-eclampsia in previous pregnancies, low (< 6th grade) educational level, a body mass index > 24 and maternal blood group AB were factors independently associated with an increased risk of pre-eclampsia. In conclusion, this study confirms that smoking in pregnancy reduces the risk of pre-eclampsia. However, the harmful consequences of smoking on pregnancy outcome far outweigh this risk reduction.

The impact of oral contraception on vulvovaginal candidiasis.

To evaluate risk factors related to sociodemographic and clinical variables, oral contraception and sexual behavior of women with recurrent vulvovaginal candidiasis, we conducted a case-control study comparing 153 patients with recurrent vulvovaginal candidiasis with both asymptomatic women with negative vaginal cultures and patients with nonrecurrent symptomatic vulvovaginal candidiasis. In logistic regression analysis, patients with recurrent Candida vaginitis were more likely than negative controls to have used any contraceptive method in the year before evaluation, to have used antibiotics in the month preceding the visit, and to have a higher number of lifetime sex partners. Compared to patients with nonrecurrent Candida vaginitis, patients with recurrent infection were more likely to use oral contraception and to have a higher frequency of monthly intercourse. The proportion of recur rent disease attributable to the pill averages 11-12%. We conclude that oral contraceptives may influence the recurrence of symptomatic vulvovaginal candidiasis.

PIP: Researchers in Italy compared data on 153 patients with recurrent vulvovaginal candidiasis (cases) with data on 306 asymptomatic patients (control group A) and data on 306 patients with nonrecurrent symptomatic vulvovaginal candidiasis (control group B). They wanted to examine the sociodemographic and clinical characteristics, sexual habits, and contraceptive histories of women with recurrent vulvovaginal candidiasis. Cases were more likely than asymptomatic women to have previously used any contraceptive method (odds ratio [OR] = 2.08 for the pill, p = 0.0032; OR = 4.15 for the IUD, p = 0.0019; OR = 2.55 for barrier methods, p = 0.014). They were also more likely to have used antibiotics in the last month before the visit (OR = 2.1; p = 0.009) and to have more lifetime sexual partners than asymptomatic women (OR = 3.82 for 7 partners; p = 0.009). Patients with recurrent vulvovaginal candidiasis were more likely than those with nonrecurrent vulvovaginal candidiasis to have used low-dose oral contraceptives (OCs) (OR = 1.59; p = 0.036) and to have a higher rate of monthly intercourse in the last 6 months (OR = 2.51 for 10 times; p = 0.048). The attributable risk of OC use for recurrent vulvovaginal candidiasis was insignificant (11-12%). These results suggest that OCs may contribute to the recurrence of symptomatic vulvovaginal candidiasis.

Maternal high-risk factors and severity of growth deficit in small for gestational age infants.

The relationship between maternal risk factors and severity of fetal growth deficit was evaluated in a population of 613 small for gestational age (SGA) infants and 784 appropriately grown controls. The severity of growth deficit among SGA infants was expressed as 'fetal growth ratio' (observed/expected birthweight, where expected birthweight is the mean birthweight of the Italian population for a given gestational age). In multivariate models, preeclampsia was the only maternal high-risk factor positively correlated with a more severe growth deficit among SGA infants. Chronic cardiac or renal maternal diseases and female fetal sex were associated with mild forms of SGA, thus showing an inverse relationship with severity of growth deficit. Finally, the association between maternal smoking in pregnancy, low (< 0.2 kg/week) maternal weight gain, low (< 50 kg) pre-pregnancy weight, severe (Hb, < 8 g/dl) maternal anaemia, low education (< 6th grade), history of a previous low birthweight infant or recurrent spontaneous abortion, nulliparity and SGA was homogeneous across the severity strata of fetal growth deficit.

Value of antenatal corticosteroid therapy in preterm birth.

This prospective observational study was designed to evaluate the magnitude of the corticosteroid-related reduction in the risk of respiratory distress syndrome (RDS), intraventricular hemorrhage and neonatal death according to different etiologic subgroups of preterm delivery. Of 380 patients delivered before 35 weeks' gestation, 155 received a complete course of dexamethasone or betamethasone to promote fetal lung maturation. In logistic models, the steroid-related reduction of RDS was greater among patients with intact membranes as opposed to patients with premature rupture of membranes (excess risk = 0.31; 95% confidence interval (C.I.) = 0.13-0.73; P = 0.007) and in patients with spontaneous preterm labor as compared with other etiologic groups (excess risk = 0.33; 95% C.I. = 0.11-0.98, P = 0.04). On the other hand, the steroid-related reduction of severe (grade III-IV) intraventricular hemorrhage was more marked in growth retarded as opposed to well-grown fetuses (excess risk = 0.15; 95% C.I. = 0.03-0.96, P = 0.04), and in planned as compared with spontaneous preterm deliveries (excess risk = 0.15; 95% C.I. = 0.03-0.96, P = 0.04). Results show that the greatest benefit from antenatal steroids appears to be in preterm deliveries with intact membranes and in planned preterm deliveries.

Antenatal and delivery risk factors simultaneously associated with neonatal death and cerebral palsy in preterm infants.

To evaluate the simultaneous effects of antenatal and delivery risk factors on neonatal death and cerebral palsy in preterm infants, we conducted a cohort study of 363 singleton pregnancies delivered between 24 and 33 weeks gestation. Neurodevelopmental outcome of the infants was evaluated at 2 years of corrected age. Risk factors associated with death or cerebral palsy were analysed by politomous logistic regression. Overall, the mortality rate was 14.6% (53/363) and the prevalence of cerebral palsy among surviving infants was 12.3% (38/310). Decreasing gestation and meconium-stained amniotic fluid were the only antenatal factors associated with increased odds for both death and cerebral palsy. The effect magnitude and the predictive value of gestational age were greater for death than for cerebral palsy. After adjustment for confounders, prolonged (> or = 48 h) rupture of membranes (odds ratio 2.98, 95% confidence interval 1.12-7.96) and male sex of the infant (odds ratio 3.01, 95% confidence interval 1.32-6.71) were significantly associated only with cerebral palsy. We conclude that neonatal death and cerebral palsy share few common antenatal risk factors. The characteristics of antenatal risk factors for cerebral palsy suggest that bacterial infestation of the amniotic cavity may be implicated in the etiology of the cerebral impairment.

Preeclampsia, preterm delivery and infant cerebral palsy.

OBJECTIVE: To evaluate the association between preeclampsia and cerebral palsy among preterm infants. STUDY DESIGN: A cohort study of 345 singleton preterm (24 to 33 weeks gestation) infants delivered at an institution where no mothers received magnesium sulphate. We investigated the relationship of preeclampsia to the development of infant cerebral palsy (spastic quadriplegia, hemiplegia or diplegia) at two years' corrected age. Potential confounders were controlled for by politomous logistic regression analysis. RESULTS: The prevalence of cerebral palsy in surviving infants from normotensive and preeclamptic pregnancies was 13.4% (38/284) and 3.3% (2/61), respectively (P=0.026 by Fisher exact test). After control for potential confounders (gestational age, infant gender, birthweight standard deviation score, mode of delivery), the likelihood of infant cerebral palsy was reduced by preeclampsia (odds ratio 0.16, 95% confidence interval=0.04-0.74 for infants from preeclamptic versus normotensive pregnancies being palsied). CONCLUSION: Among preterm infants, the protective effect of preeclampsia against cerebral palsy is manifest in the absence of magnesium sulphate utilization.

Sociodemographic and clinical variables modifying the smoking-related risk of low birth weight.

OBJECTIVE: The purpose of the study was to evaluate the sociodemographic and clinical variables modifying the smoking-related risk of low birth weight (< 2500 g). METHOD: This case-control study included a population of 967 singleton low birth weight deliveries and 967 selected controls. Unconditional logistic regression analysis was used to test statistical significance of the interactions between smoking in pregnancy and other risk factors for low birth weight. RESULTS: Increasing maternal age and parity potentiate the smoking-related risk of a low birth weight infant. The effect of maternal smoking on the risk of low birth weight was significantly increased in patients with a history of previous spontaneous abortion (excess risk 2.30, 95% C.I. 1.24-4.27) and in patients of high compared with patients of intermediate or low social class (excess risk 1.97, 95% C.I. 1.1-3.57). Smokers with less than two prenatal visits per trimester were at significantly greater risk of delivering a low birth weight infant (excess risk 2.36, 95% C.I. 1.14-4.87) than their counterparts with more frequent prenatal visits. Among clinical variables, the effect of maternal smoking on the risk of low birth weight was significantly increased in women with a history of first trimester hemorrhage during the current pregnancy (excess risk 2.67, 95% C.I. 1.30-5.49). CONCLUSIONS: The smoking-related risk of low birth weight is very high in some subgroups of women. Identification of these subgroups could be important for prenatal counseling.

Pregnancies complicated by idiopathic intrauterine growth retardation. Severity of growth failure, neonatal morbidity and two-year infant neurodevelopmental outcome.

We evaluated the impact of the severity of intrauterine growth retardation (IUGR) measured as the proportion of expected birth weight (birth weight x 100/median birth weight) on short-term neonatal complications and two-year infant neurodevelopmental outcome. The study was carried out on 236 singleton pregnancies complicated by idiopathic IUGR. The rates of bradycardia, respiratory distress syndrome, hypocalcemia, ventilatory support, apneic crises, transient neurologic signs and poor neonatal outcome (neonatal death or cerebral palsy) significantly correlated with the increasing severity of IUGR. In logistic regression analysis more severely growth retarded infants (< 67.5% of expected birth weight) had higher rates of bradycardia, respiratory distress syndrome, hypocalcemia and bacterial sepsis when compared with those less severely affected (84-67.5% of expected birth weight). In pregnancies complicated by idiopathic IUGR, most short-term neonatal complications are inversely related to the severity of growth failure as evaluated by the proportion of expected birth weight.

[Genital infections as a cause of abortion in the first trimester of pregnancy. Review of the literature]. / Le infezioni genitali quali causa di aborto nel primo trimestre di gravidanza. Revisione della letterature.

The rate of spontaneous abortion from embryo-fetal infection is believed to range from 10 to 15%. This figure, however, is likely to be underestimated because of subclinical abortions occurring at the earliest stages of gestation that go undiagnosed. The actual frequency of infections resulting in 1st trimester spontaneous abortion is therefore unknown, whereas the impact of infectious agents in the TORCH group on the pathogenesis of such event is well known, although the pathogenetic mechanisms are not well understood. A wide range of microorganisms have been isolated by several investigators from the lower genital tract of women with 1st trimester spontaneous abortion. No causative relationship of HIV-1 infection to spontaneous abortion has been established yet. The diagnosis of abortion from infection can only be made retrospectively based on histologic examination of fetal and placental tissue and isolation on culture of the infectious agent assumed to have caused infection.

Prenatal diagnosis of congenital anomalies.

Up till the early 1970s, prenatal diagnosis of congenital anomalies was primarily aimed at detecting chromosomal abnormalities by amniocentesis.1. Over the last two decades, prenatal diagnosis has greatly benefited from advances in ultrasound technology and in our ability to detect microscopic and submicroscopic chromosome abnormalities as well as single gene disorders, leading to substantive improvements in detection of such congenital anomalies.2 At present, invasive prenatal diagnosis continues to be the gold standard for pregnancies at increased risk for chromosomal anomaly or other genetic disease, with chorionic villus sampling being the procedure of choice for the first trimester,3 whereas mid-trimester amniocentesis continues to be the most common form of invasive procedure for prenatal diagnosis.4 Still, invasive techniques are restricted to subgroups at risk for anomalies, for whom such time-consuming procedures are believed to be cost-effective, also accounting for procedure-related abortive risks. In the low-risk population prenatal diagnosis generally consists of screening procedures by means of ultrasound and maternal serum biochemistry.

Effect of preterm premature rupture of membranes on neurodevelopmental outcome: follow up at two years of age.

OBJECTIVE: To evaluate the impact of preterm premature rupture of membranes on the neurodevelopmental outcome of infants, assessed at two years of age. DESIGN: A prospective observational study of surviving preterm infants born after premature rupture of membranes and of infants born after spontaneous preterm labour with intact membranes. The study was carried out in the period 1986 to 1991. SETTING: Pavia, Italy. SUBJECTS: One hundred and forty singleton infants born prematurely after premature rupture of membranes between 24 and 34 weeks of gestation and 120 controls of similar gestational age born after spontaneous preterm labour with intact membranes. MAIN OUTCOME MEASURES: Infant neurodevelopmental outcome at two-year follow up. RESULTS: After adjustment, by logistic analysis for the effect of gestational age and birthweight, infants born after premature rupture of membranes were more likely to have severe neurodevelopmental impairment (spastic tetraplegia and/or Bayley mental developmental index < 71) than controls (adjusted OR 5.75, 95% CI 1.22-27.18). Multivariate analysis of linear trend showed a statistically significant relation of duration of membrane rupture to occurrence of severe intraventricular haemorrhage, cystic periventricular leucomalacia and moderate to severe infant neurodevelopmental impairment. CONCLUSION: Infants born after prolonged premature rupture of membranes are at higher risk of subsequent moderate to severe neurodevelopmental impairment than those born after spontaneous labour with intact membranes.

Perinatal factors and 2-year minor neurodevelopmental impairment in low birth weight infants.

Perinatal factors were investigated in 53 low birth weight infants with minor neurodevelopmental dysfunction at 2-year follow-up and in 106 consecutive controls matched for gestational age and birth weight (within 100-gram intervals). The obstetrical history, as evaluated by the obstetrical optimality score, was significantly worse in the cases than in controls (obstetrical optimality score = 50.9 +/- 5.9 vs. 53.2 +/- 6.9, p = 0.019 by Mann-Whitney test). Multiple conditional logistic regression analysis showed that after adjustment for socioeconomic status and education of the mother, a low number (< 3) of prenatal visits, and a third trimester hemorrhage were the only antenatal factors significantly associated with an increased risk of minor infant neurodevelopmental impairment. Neonatal acidosis (pH < 7.2 in the first 24 h of life) and male gender were additional significant perinatal risk factors. Only a few antenatal and perinatal factors are correlated with subsequent minor neurodevelopmental impairment in low birth weight infants.