The Association between Advanced Maternal Age and the Manifestations of Preeclampsia with Severe Features.

This retrospective cohort study aimed to explore the association between advanced maternal age and the clinical manifestations as well as laboratory parameters of preeclampsia with severe features. This study included 452 patients who were diagnosed with preeclampsia with severe features. The clinical and laboratorial characteristics of patients with preeclampsia with severe features aged ≥40 years old (study group) were compared to those of patients aged <40 years old (control group). Multivariant analysis was applied to assess the association between advanced maternal age and the manifestations of preeclampsia with severe features, adjusting for the variables that exhibited significant differences between the study and control groups. The multivariate analysis revealed that a maternal age of ≥40 years old was an independent risk factor for acute kidney injury (OR = 2.5, CI = 1.2-4.9, p = 0.011) and for new-onset postpartum preeclampsia (OR = 2.4, CI = 1.0-5.6, p = 0.046). Conversely, a maternal age ≥ 40 years old was associated with a reduced risk of HELLP syndrome (OR = 0.4, CI = 0.2-0.9, p = 0.018) and thrombocytopenia (OR = 0.5, CI = 0.3-0.9, p = 0.016) compared to that of the patients < 40 years of age. In conclusion, this study demonstrates that maternal age is significantly associated with the clinical manifestations and laboratory parameters of preeclampsia with severe features, highlighting the importance of age-specific management.

Azathioprine and 6-mercaptopurine-induced intrahepatic cholestasis of pregnancy: Case report and review of the literature.

OBJECTIVE: Azathioprine, a prodrug of 6-mercaptopurine (6-MP), is used in the treatment of inflammatory bowel disease and may be continued during pregnancy. Acute cholestatic liver injury has been reported to occur with azathioprine. We aimed to examine azathioprine related cholestasis effect on pregnancy complications and outcome. CASE REPORT: We present a unique case of 6-MP-induced severe intrahepatic cholestasis of pregnancy (ICP) that required meticulous combined therapy including plasma exchange. The symptoms resolved following 6-MP withdrawal. A literature review revealed 11 pregnancies complicated by early-induced severe ICP among women treated with azathioprine or 6-MP. CONCLUSION: We recommend weekly bile acid level tests for pregnant women treated with azathioprine or 6-MP, beginning early in the second trimester of pregnancy, and the prompt discontinuation of treatment upon establishment of an ICP diagnosis.

Pravastatin is useful for prevention of recurrent severe placenta-mediated complications - a pilot study.

BACKGROUND: Preeclampsia with severe features and other severe placenta-mediated complications may be life threatening to mother and fetus, especially when they are recurrent. Recurrence of pregnancy complications is common, however, when combined treatment with low molecular weight heparin and low dose aspirin fails, there are not any proven therapeutic options for prevention of recurrence of obstetrical complications. OBJECTIVE: We aimed to determine the impact of adding pravastatin to low molecular weight heparin and low dose aspirin for improving pregnancy outcome in women with severe recurrent placenta-mediated complications. DESIGN: A retrospective study of 32 women with severe recurrent placenta-mediated complications (preeclampsia with severe features, placental abruption, severe intrauterine growth retardation or intra uterine fetal death) in spite of treatment with low molecular weight heparin and low dose aspirin in previous pregnancy. All women were treated in the index pregnancy with 20 mg pravastatin starting at 12 weeks, with low molecular weight heparin and low dose aspirin. Antiphospholipid syndrome was evident for 10 of the 32 women. RESULTS: In the index pregnancy, only one woman had recurrence of severe placenta-mediated complications. Gestational age at delivery in the index pregnancy compared to previous pregnancy when women were treated with low molecular weight heparin and low dose aspirin was 36.5 ± 1.7 vs. 32 ± 3.6 weeks, and mean birth weight 2691 ± 462 vs. 1436 ± 559 grams, compared to previous pregnancy when women were treated with low molecular weight heparin and low dose aspirin (p < .001 for both). Of the 17 women with previous preeclampsia with severe features, 15 had no recurrence of preeclampsia and 2 women had mild preeclampsia at term. Of the 8 women with previous severe intrauterine growth retardation, all delivered at significant higher gestational age compare to previous pregnancy, [37.0 ± 1 vs. 34 ± 3 weeks, (p < .05)] with higher mean birth-weight [2648 ± 212 vs. 1347 ± 465 grams, (p = .05)]. Of the 3 women with previous placental abruption, one delivered at 32 weeks due to non-reassuring fetal heart monitoring, one woman was delivered at 36 weeks due to mild preeclampsia, and one woman underwent elective induction of labor at 37 weeks with no intrauterine growth retardation. Of the 4 women with previous recurrent intrauterine fetal death, 3 women delivered at 37 weeks after elective induction, and one woman at 30 weeks with a birthweight of 960 grams due to severe intrauterine growth retardation. CONCLUSIONS: Additive treatment with pravastatin to low molecular weight heparin and low dose aspirin may be a promising option in cases of previous severe recurrent placenta-mediated complications.

Progression from isolated gestational proteinuria to preeclampsia with severe features.

INTRODUCTION: The association between the degree of isolated gestational proteinuria and preeclampsia with severe features and other placental-mediated complications is controversial. The aim of this study was to evaluate whether a higher isolated proteinuria level is associated with an increased frequency of preeclampsia with severe features. MATERIAL AND METHODS: This retrospective cohort study included pregnant women who were past 24 weeks of gestation and were diagnosed as having new-onset proteinuria ≥300 mg in a 24-h urine collection. Exclusion criteria included diagnosis of preeclampsia within 72 h from admission, chronic renal disease or chronic hypertension. The study population was divided into tertiles by proteinuria level and the association with preeclampsia with severe features was assessed in both bivariable and multivariable analysis. The main outcome measures was the development of preeclampsia with severe features. RESULTS: Overall, 165 women were diagnosed with isolated gestational proteinuria, and 38 (23.0%) of them developed preeclampsia with severe features. Women in the increasing proteinuria tertile were more likely to develop preeclampsia with severe features (5.5%, 21.8%, 41.8%, respectively; p = 0.004). A multivariable logistic regression model controlling for background characteristics as well as gestational age at diagnosis, blood pressure, and kidney and liver function tests showed an increased risk of 14% to develop preeclampsia with severe features for every 500-mg rise in proteinuria level (adjusted odds ratio = 1.14, 95% confidence interval 1.03-1.27). CONCLUSIONS: A higher isolated gestational proteinuria level was associated with an increased risk to develop preeclampsia with severe features among pregnant women past 24 weeks of gestation.

Diagnostic accuracy of random urinary protein-to-creatinine ratio for proteinuria in patients with suspected pre-eclampsia.

PURPOSE: To evaluate the correlation between urine protein/creatinine ratio (UPCR) and proteinuria in a 24-h urine collection and to calculate the predicative accuracy of different cutoffs of UPCR for the diagnosis of proteinuria. METHODS: A retrospective cohort study including women who admitted for the evaluation for suspected preeclampsia (PET) beyond 20 weeks of gestation in a single tertiary center. Both UPCR test and quantification of proteinuria using 24-h urine collection were obtained during their index hospitalization no more than 48 h apart. Women with pre-existing diabetes mellitus, known renal disease or proteinuria prior to pregnancy or chronic hypertension were excluded. Predictive accuracy of UPCR for several cutoffs of proteinuria was evaluated. Multivariate logistic regression analysis was used to assess diagnostic accuracy of UPCR in sub-populations according to obstetrical characteristics. RESULTS: Overall 463 patients were included. Of them 316 (68.3%) have 24-h urine protein collection of ≥ 300 mg/day. Mean gestational age at evaluation was 34.0 ± 3.4 weeks. Median (and interquartile range) time interval between UPCR and 24-h urine collection was 1.8 (1.6-1.9) days. Sensitivity and specificity of UPCR of 0.3 for predicting proteinuria ≥ 300 mg/day were 90.1% and 63.3%, respectively. The corresponding values for difference proteinuria cutoffs: ≥ 1000 mg/day and 5000 mg/day were 98.4, 100% and 29.1, 36.0%, respectively. The optimal UPCR thresholds for 24-h urine protein collection of ≥ 300 mg/day, ≥ 1000 mg/day and 5000 mg/day were 0.31, 0.70 and 2.49, respectively. The predictive accuracy of UPCR > 0.30 in predicting proteinuria was unaffected by demographic and obstetrical characteristics as maternal age, pre-pregnancy BMI, gestational age at examination, creatinine levels or by multiple gestation [adjusted OR 18.27 (95% CI 9.97-33.47)]. CONCLUSION: UPCR was strongly correlated with various cutoffs of proteinuria obtained by 24-h urine collection. UPCR cutoff varied depending on the specific measured outcome. This correlation was not affected by gestational age at examination.

Fetal gender and umbilical cord characteristics at birth.

OBJECTIVE: To determine fetal gender on umbilical cord parameters. METHODS: Umbilical cords were prospectively collected from uncomplicated, singleton, term pregnancies, which ended either by elective cesarean section or spontaneous vaginal delivery. Data regarding obstetrical history and pregnancy outcome were collected. Various cord parameters were examined including, length, number of coils, umbilical cord index (UCI), which demonstrate the ratio between number of coils and cord length, site of placental insertion, direction of coiling and the presence of true knots. RESULTS: Overall, 154 umbilical cords were collected, of them 84 from male and 70 from female newborns. No differences were found regarding obstetrical history parameters or pregnancy outcome between the groups. The umbilical coiling index was significantly higher in female compared to male newborns (0.183 coils/cm versus 0.157 coils/cm, p=.006) due to higher number of cord coils (12.25 ± 5.31 vs. 10.17 ± 3.96, p=.007), with no difference in cord length (66.48 vs. 64.61 cm, p=.372). These differences remained statistically significant even after correction for gravidity, parity and gestational age using multiple linear regression analysis. CONCLUSION: Female newborns having higher umbilical cord index, compared to male as a result of more coils, with no length dissimilarity.

Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. METHODS: We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. FINDINGS: We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 µmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 µmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 µmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001). INTERPRETATION: The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 µmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. FUNDING: Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust.

The Effect of Pregnancy on Disease Activity in Patients with Psoriatic Arthritis.

OBJECTIVE: To evaluate the effect of pregnancy on disease activity in psoriatic arthritis (PsA). METHODS: This is a retrospective case series. Review of the medical files of all female patients followed at the PsA clinic of 2 medical centers identified those with at least 1 pregnancy during followup and 1 visit during or soon after pregnancy. RESULTS: Twenty-five women with PsA (out of 107 women of reproductive age followed up in our PsA clinics) and 35 pregnancies were enrolled. Thirty-three pregnancies resulted in live healthy babies. In the whole group, there was no significant change in disease activity throughout pregnancy, while in 16 (48%) of pregnancies, patients worsened during the first postpartum year. In 15 out of 21 pregnancies, in which the women had been treated before conception with biologics, treatment was discontinued close to pregnancy or during the first trimester. Five of those 15 patients had been classified as having mild to severe PsA activity prior to pregnancy. That number increased to 8, 9, and 14 during the first and second trimesters and postpartum period, respectively. There was no significant change in degree of disease activity in 6 patients whose biologics were continued beyond the first trimester. Improvement in disease activity was observed during pregnancy among the nonbiologics-treated patients. Corticosteroids were initiated or the dosage was increased during 6 pregnancies, all involving patients whose biologics were stopped before pregnancy. CONCLUSION: Continuation of biologics therapy was associated with a low level of disease activity and a low probability of flare during pregnancy. Stopping treatment with biologics before pregnancy is associated with flare during pregnancy and the postpartum period.

The role of HCG increment in the 48h prior to methotrexate treatment as a predictor for treatment success.

OBJECTIVE: To evaluate the role HCG change in the 48h prior to methotrexate treatment as a predictor for treatment success. STUDY DESIGN: Medical records of all women who were diagnosed with ectopic pregnancy between January 2001 and June 2013 were reviewed. Four hundred and nine patients received methotrexate due to ectopic pregnancy. The "single dose" methotrexate protocol with 50mg/m2 was administered to patients with progressing ectopic pregnancy. HCG levels in days 1, 4 and 7 were used to evaluate methotrexate treatment success. The percentage of HCG change in the 48h prior to methotrexate treatment was compared between patients who were successfully treated and those who failed treatment with methotrexate. RESULTS: Single dose methotrexate was successful in 309 patients (75.4%, success group). The medians of HCG change in the 48h prior to methotrexate administration were significantly higher in the "failure group" (21% vs. 4%, p<0.01). In a logistic regression analysis, the of HCG percent increment prior to methotrexate administration was shown to be an independent predictor for treatment outcome. Receiver operator characteristic curve for HCG percent change was 0.751, at a cutoff value of HCG increment <12% the positive predictive value for treatment success reached 86%. CONCLUSIONS: Percentage of HCG increment in the 48h prior to methotrexate administration is an independent predictor for methotrexate treatment success. HCG increment <12% prior to methotrexate treatment is a good predictor for treatment success.

Adnexal Torsion in Postmenopausal Women: Clinical Presentation and Risk of Ovarian Malignancy.

STUDY OBJECTIVE: To investigate the clinical presentation, operative outcome, and incidence of malignancy in postmenopausal women who were diagnosed with adnexal torsion. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Tertiary university-affiliated hospital. PATIENTS: Postmenopausal women diagnosed with adnexal torsion between 1995 and 2014 (study group) were reviewed and compared with 220 premenopausal patients diagnosed with adnexal torsion during the same time period. INTERVENTION: Demographic data, clinical signs and symptoms, and intra- and postoperative characteristics were compared between the 2 groups. MEASUREMENTS AND MAIN RESULTS: During the study period 44 postmenopausal women were diagnosed with adnexal torsion. Continuous dull pain was the most common presenting symptom in the postmenopausal group (57%), whereas acute-onset sharp pain was the predominant symptom in the premenopausal group (86%). The time interval from admission to surgery was significantly longer in the postmenopausal group (24 vs 6 hours, p < .001). Laparoscopic surgery was performed in 84.5% of the cases in the premenopausal group, whereas it was carried out in only 50% of cases in the postmenopausal group (p < .001). Four women in the postmenopausal group were diagnosed with malignancy, whereas only 1 case of malignancy was found in the premenopausal group (9% vs .4%, respectively; p = .003). CONCLUSIONS: Adnexal torsion in postmenopausal women is an uncommon event with a unique presentation. Because ovarian malignancy is not an uncommon finding in this group of patients, preparation for more extensive surgery should be contemplated.

Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is known to be associated with fetal complications. It recently was suggested to be associated possibly with preeclampsia (PET) as well. The objective of this study was to investigate that possibility. STUDY DESIGN: The study group included 78 women (54 singleton and 24 twin pregnancies) who had been diagnosed with ICP based on clinical presentation, elevated liver enzymes, and elevated total bile acids (>10 µmol/L). Disease severity was based on total bile acids levels as being severe (>40 µmol/L), moderate (20-40 µmol/L), or mild (10-20 µmol/L). The course of disease was reviewed carefully in each case. The control groups were comprised of apparently healthy women with singleton (n = 200) and twin (n = 100) pregnancies that were drawn randomly from a computerized registry of all the deliveries in our institution during the study period. RESULTS: The total incidence of PET was significantly higher for the patients with ICP who had singleton and twin pregnancies compared with the control groups (singletons: 7.4% vs 1.5%; P < .05; twins: 33.3% vs 6.2%; P < .05, respectively). The incidence of severe PET was also significantly higher in both singleton (11-fold) and twin (8-fold) pregnancies compared with control subjects. Severe ICP, but not mild ICP, was a major risk factor for PET among women with either singleton or twin pregnancies. The timing of the initial presentation of ICP had no effect on PET incidence rates. Preeclampsia occurred usually 2-4 weeks after the diagnosis of ICP, and proteinuria preceded elevated blood pressure in all cases. Moreover, the total bile acid levels among 33 women who were diagnosed as having PET, but not ICP, were within normal range. CONCLUSION: ICP increases the incidence of PET; severe disease was a major risk factor for preeclampsia. Therefore, we strongly suggest including routine evaluation for preeclampsia in the treatment of women with moderate and severe ICP.

Visual deterioration during pregnancy due to skull base tumors compressing the optic apparatus.

Intracranial tumors may rapidly enlarge during pregnancy. When the tumor abuts the optic apparatus, tumor growth may cause visual deterioration. The decisions regarding the management of these tumors should take into consideration visual function, fetal and maternal safety, and the ability for total resection of the tumor. The objective of the study was to describe our experience and to establish principles for management of intracranial tumors compressing the optic apparatus that present during pregnancy or in the early post partum period. A retrospective case-series review was conducted. Women who presented with visual deterioration either during pregnancy or in the early post partum period due to an intracranial tumor were included. Neurosurgical and obstetrical data were collected from the patients' hospital files and outpatient clinic records. Between 2005 and 2011, nine pregnant women with visual deterioration were diagnosed and treated. Of them, four underwent a neurosurgical procedure during pregnancy. Of the five patients who underwent surgery for tumor resection after delivery, three required urgent cesarean section either due to acute visual deterioration or obstetrical reasons. There was no maternal or fetal mortality and a good overall neonatal outcome was achieved. Improvement in visual acuity and visual fields was achieved in all patients. Postoperative complications included two cases of CSF leak, which resolved after treatment. Visual deterioration during pregnancy due to tumors that compress the optic apparatus requires treatment by a multi-disciplinary team. Surgery is well tolerated by mother and fetus during early and midpregnancy; thus, in cases where visual deterioration is detected, delay of surgery is not justified.

The influence of prolonged preterm premature rupture of the membranes on neonatal outcome of the presenting and non-presenting twin.

OBJECTIVE: To compare the neonatal outcome in twin gestations complicated by prolonged preterm premature rupture of membranes (PPROM). STUDY DESIGN: Between the years 2000 and 2010 we identified 48 women with twin pregnancies who were diagnosed as having PPROM and a latency period to delivery >24h. We compared the neonatal morbidity and mortality between the presenting and non-presenting twins, assuming that the rupture occurred in the lower sac. Importantly, in 30 women we were able to identify the location of the ruptured sac by ultrasound examination demonstrating oligohydramnion. In these 30 cases, neonatal outcome of fetuses in the ruptured sac and those in the intact sac were compared. RESULTS: The median gestational age was 31 weeks (range 28-33) with a median latency period between PPROM and delivery of 9 days (range 1-18). Of the identified ruptures 90% (27/30) occurred in the lower sac (presenting twin). There was no significant difference between the presenting and non-presenting twin in terms of neonatal morbidity and mortality. Moreover, no difference was found when fetuses with ruptured sac were compared to those with intact membrane sac. Importantly, the outcomes were not affected by the length of the latency period. CONCLUSION: The current study results demonstrated that the outcome of fetuses exposed to prolonged preterm rupture of membranes is similar to that of fetuses with intact membranes. Our data suggest that rupture of membranes per se did not cause any deleterious clinical manifestations or lead to clinical discordant inflammation and poor neonatal outcome, supporting a conservative management of twin pregnancies with PPROM.

Placental abruption remote from term associated with Q Fever infection.

BACKGROUND: It has been suggested that Q fever infection in pregnancy is associated with various maternal and neonatal adverse outcomes, including intrauterine growth restriction, stillbirth, preterm delivery, intrauterine fetal death, and oligohydramnios. CASE: We describe the cases of two pregnant women remote from term who presented with premature contractions and fever of unknown origin. During their hospitalizations, they had development of near-complete placental abruption. In both cases, immediate delivery ensued. Fever of unknown origin work-up revealed chronic Q fever infection, and polymerase chain reaction investigation of the placenta demonstrated chronic Q fever placentitis. CONCLUSION: Q fever placentitis may result in placental abruption remote from term. Therefore, in endemic areas, the diagnosis of Q fever requires appropriate surveillance and prenatal care.

Severe pregnancy complications are associated with elevated factor VIII plasma activity.

The objective of this study is to investigate the prevalence of elevated factor VIII activity among women with severe complications of pregnancy. The study group included 49 patients with a previous history of pregnancy complications: severe preeclampsia (n = 9); intrauterine fetal death (IUFD) (n = 9); severe intrauterine fetal growth restriction (IUGR) (n = 12); IUGR and preeclampsia (n = 7); preeclampsia and placental abruption (n = 2); IUFD and IUGR (n = 5); and abruptio placenta (n = 5). The control group included 49 healthy women who had had at least one normal pregnancy. Seventeen women of the study group (34.6%) had elevated factor VIII activity compared to one woman (2.1%) in the control group (P < 0.05). The mean level of factor VIII was 159 ± 52% and 88 ± 17.4% of normal activity (mean  ±  SD, t-test, P < 0.05). Importantly, 10 women of the study group (20.4%) had only elevated factor VIII activity with no other known thrombophilia compared to one woman (2.1%) in the control group (P < 0.05). Elevated plasma activity of factor VIII might be a risk factor for severe pregnancy complications.

Neurosurgery and pregnancy.

BACKGROUND: Pregnant women with pathological conditions requiring a neurosurgical intervention pose a unique therapeutic challenge. Changes in normal physiology add to the complexity of patient management. We describe our experience in treating various neurosurgical diseases in parturient women. METHODS: Thirty-four pregnant and early postpartum women were treated at our center between 2003 and 2010. The general guideline used in these patients (now deserving re-evaluation based on the presented data) was to postpone surgery until the patient reached term (weeks 34-38 of gestation) unless there was evidence of a life- or function-threatening condition, in which case surgery was promptly performed. RESULTS: Sixteen patients underwent neurosurgical intervention during pregnancy between 11 to 34 weeks of gestation (7 tumor, 3 vascular, 2 VP shunt, 2 spinal, 2 trauma). Thirteen women underwent a neurosurgical procedure after delivery (12 tumor, 1 spine), and 5 women were treated conservatively (2 vascular lesions, 3 trauma). Three patients underwent abortions (one spontaneous and two elective). The other 31 women delivered at 30-42 weeks' gestation. Of 12 patients whose definitive neurosurgical procedure was initially delayed, 5 were not able to complete their pregnancy naturally. Of 21 patients that underwent a cesarean section (CS), 3 were performed urgently. Although two pairs of twins and two singletons had an initial low Apgar score (<7), the outcome for all the neonates was good. Neurosurgical outcome was satisfactory. CONCLUSIONS: Our experience demonstrates the safety of neurosurgical intervention and anesthesia during pregnancy. Delaying intervention often resulted in maternal deterioration and urgent intervention. Thus, pregnancy by itself should not be considered a major contraindication for performing a neurosurgical procedure, which should be considered early rather than late in most patients.

Low molecular weight heparin treatment during subsequent pregnancies of women with inherited thrombophilia and previous severe pregnancy complications.

OBJECTIVES: The aim of this study was to investigate the effect of low molecular weight heparin (LMWH) on incidence of adverse outcome in women with thrombophilias and previous severe pregnancy complications. MATERIALS AND METHODS: The study included 116 women with history of severe preeclampsia, fetal growth restriction (FGR)  ≤5th percentile, severe placental abruption and stillbirth  >20 weeks carrying factor V Leiden or prothrombin mutations, or protein S or C deficiency. Eighty-seven women referred to us for follow-up were treated with LMWH starting from weeks 5-15 (study group, A). Twenty-nine non-treated women referred only for delivery in our institution constituted the control group (B). RESULTS: The incidence of severe pregnancy complications in previous pregnancies was similar in both groups. Following treatment with LMWH, the incidence of severe preeclampsia was 4.6% in group A compared to 21% in group B, p = 0.007. The incidence of FGR was 2.3% in group A compared to 21% in group B, p = 0.03. The incidence of stillbirth or placental abruption was 0% in group A compared to 7% in group B, p = 0.06. The total incidence of adverse outcome was 7% in group A compared to 55% in group B, p = 0.0001. CONCLUSION: LMWH treatment of women with previous severe pregnancy complications and thrombophilias significantly reduces the rate of recurrence.

Low molecular weight heparin versus no treatment in women with previous severe pregnancy complications and placental findings without thrombophilia.

Low molecular weight heparin (LMWH) treatment has been recommended for pregnant women with previous adverse pregnancy and who were diagnosed as having a thrombophilia. We now examined the effect of LMWH on pregnant women without thrombophilias who had severe pregnancy complications and placental vasculopathy in an earlier pregnancy. Seventy-two women with a history of severe preeclampsia, fetal growth restriction (FGR) less than fifth percentile, severe placental abruption and/or stillbirth after 20 weeks, whose thrombophilia workup was negative, were enrolled. Placental vasculopathy was defined as villous infarcts, fibrinoid necrosis of decidual vessels, fetal vessel thrombosis, evidence of placental abruption and perivillous fibrin deposition. The study group consisted of 32 pregnant women who were treated with LMWH and 40 pregnant women who were not treated with LMWH (control group) in their ensuing pregnancy in our institution between 2003 and 2007. The incidences of severe preeclampsia, FGR, placental abruption and stillbirth in the previous pregnancies were similar for both groups. The incidences of severe preeclampsia and placental abruption in the study group in the index pregnancy were significantly lower than the control group (3.13 versus 20%, P = 0.03; and 0 versus 15%, P = 0.03, respectively). The respective incidence of FGR was 6.25 versus 22.5%, and of overall adverse outcome was 9.4 versus 60% (P = 0.001). Treatment with LMWH may reduce the rate of the recurrence of severe pregnancy complications and significant placental vasculopathy in women without thrombophilias.

Hypoxia in human trophoblasts stimulates the expression and secretion of connective tissue growth factor.

The mechanisms underlying cellular injury when human placental trophoblasts are exposed to hypoxia are unclear. Connective tissue growth factor (CTGF) mediates cell injury and fibrosis in diverse tissues. We hypothesized that hypoxia enhances the production of CTGF in primary term human trophoblasts. Using cultured term primary human trophoblasts as well as villous biopsies from term human placentas, we showed that CTGF protein is expressed in trophoblasts. When compared with cells cultured in standard conditions (FiO2 = 20%), exposure of primary human trophoblasts to low oxygen concentration (FiO2 = 8% or