Botulinum Toxin Injection for Internal Rotation Contractures in Brachial Plexus Birth Palsy. A Minimum 5-Year Prospective Observational Study.

BACKGROUND: Brachial plexus birth palsy is frequently associated with internal rotation contractures of the shoulder as a result of muscle imbalance. The purpose of this study is to assess the effect of botulinum toxin A (BTX-A) injection in the subscapular (SC) muscle on external rotation and the need for tendon transfer for external rotation of the shoulder. METHODS: A prospective comparative study was performed including 15 consecutive patients treated with BTX-A and a historic control group of 67 patients with mean age 30 months (SD 10). The BTX-A injection (2 IU/kg body weight) was performed immediately following MRI under general anesthesia in the SC muscle. Passive external rotation, the need for tendon transfer surgery, glenohumeral deformity, and muscle degeneration were evaluated. The hazard ratio for no relapse of internal rotation contracture after BTX-A injection compared with no BTX-A injection was calculated. RESULTS: In the BTX-A group, the passive external rotation in adduction increased from -1 degree (95% CI, -10 to 8) to 32 degrees (95% CI, 17-46) at 3 months and 6 patients were indicated for surgery compared with a decline from -2 degrees (95% CI, -7 to 3) to -11 degrees (95% CI, -17 to -6) in the control group with 66 indications for surgery. At 5 years of follow-up, 10 patients in the BTX-A group were indicated for surgery with a hazard ratio of 4.0 (95% CI, 1.9 to 8.4). CONCLUSIONS: BTX-A injection in the SC muscle of brachial plexus birth palsy patients can reduce internal rotation contractures and subsequently the need for tendon transfer surgery. At 5 years of follow-up a relapse was seen in 67% of the patients treated with BTX-A. Because at MRI less SC degeneration was found in the good responders on BTX-A treatment, this group seems to be the best target group. Further research is needed on patient selection for BTX-A injection including glenohumeral deformity, SC degeneration, as well as doses of BTX-A to be used. LEVEL OF EVIDENCE: Level II-prospective comparative study.

Memory CD4(+)CCR5(+) T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1.

Despite potential clinical importance, target cells for mother-to-child transmission of HIV-1 have not yet been identified. Cord blood-derived CD4(+) T cells are largely naive and do not express CCR5, the mandatory coreceptor for transmitted HIV-1 R5 strains in infants. In the present study, we demonstrate that in the human fetal and infant gut mucosa, there is already a large subset of mucosal memory CD4(+)CCR5(+) T cells with predominantly a Th1 and Th17 phenotype. Using next-generation sequencing of the TCRß chain, clonally expanded T cells as a hallmark for memory development predominated in the gut mucosa (30%), whereas few were found in the lymph nodes (1%) and none in cord blood (0%). The gut mucosal fetal and infant CD4(+) T cells were highly susceptible to HIV-1 without any prestimulation; pol proviral DNA levels were similar to infected phytohemagglutinin-stimulated adult PBMCs. In conclusion, in the present study, we show that extensive adaptive immunity is present before birth and the gut mucosa is the preferential site for memory CD4(+) T cells. These CD4(+)CCR5(+) T cells in the infant mucosa provide a large pool of susceptible cells for ingested HIV-1 at birth and during breastfeeding, indicating a mucosal route of mother-to-child transmission that can be targeted in prevention strategies.

Association of three different techniques to measure blood pressure in the first trimester with the development of hypertensive disorders of pregnancy.

OBJECTIVE: It is not known whether automated devices for measuring blood pressure perform better than conventional sphygmomanometry in predicting preeclampsia. This study compares two different automated devices with conventional sphygmomanometry for their association with development of preeclampsia or gestational hypertension. DESIGN: Prospective observational cohort study. SETTING: University hospital, Amsterdam, the Netherlands. POPULATION: 289 healthy normotensive women of whom 235 were nulliparous and 44 parous with preeclampsia in a previous pregnancy. METHODS: At 8-11 weeks of pregnancy, blood pressure was measured with two different automated devices (continuous finger arterial pressure waveform registration and ambulatory blood pressure monitoring) and with conventional sphygmomanometry. MAIN OUTCOME MEASURES: Preeclampsia and gestational hypertension. RESULTS: Blood pressure in the first trimester, as measured with all three methods, was significantly higher in women who developed preeclampsia or gestational hypertension. After adjustment for previous preeclampsia, the point estimate of the odds ratios for association with later preeclampsia for both automated devices were comparable and higher than for conventional sphygmomanometry; however, differences were not statistically significant. The odds ratio (95% confidence intervals) for every 1 mmHg pressure increase of mean arterial pressure was 1.08 (1.02-1.15) for sphygmomanometry, 1.17 (1.09-1.27) for finger arterial pressure waveform registration, and 1.17 (1.07-1.27) for ambulatory blood pressure monitoring. Results were comparable if preeclampsia and gestational hypertension were analyzed together. CONCLUSION: Blood pressure in the first trimester was associated with the development of hypertensive disorders of pregnancy. No significant differences were found between measurements by automatic devices compared with conventional sphygmomanometry.

The functions of microparticles in pre-eclampsia.

Pre-eclampsia (P-EC), a heterogenic multisystem disorder characterized by hypertension and proteinuria, usually develops in the second half of pregnancy. The incidence is 2 to 5%, and P-EC is therefore a major cause of maternal and perinatal morbidity and mortality. Although the exact etiology is unknown, placental factors released into the maternal circulation lead to systemic maternal inflammation and endothelial dysfunction. Growing evidence indicates that placenta-derived microparticles, best known as syncytiotrophoblast microparticles (STBM), are important among these factors. This review provides an overview of the presence and function(s) of STBM and other cell-derived microparticles and exosomes.

Antenatal screening for HIV, hepatitis B and syphilis in the Netherlands is effective.

BACKGROUND: A screening programme for pregnant women has been in place since the 1950s in the Netherlands. In 2004 universal HIV screening according to opting out was implemented. Here, we describe the evaluation of the effectiveness of antenatal screening in the Netherlands for 2006-2008 for HIV, hepatitis B virus (HBV) and syphilis in preventing mother-to-child transmission, by using various data sources. METHODS: The results of antenatal screening (2006-2008) were compared with data from pregnant women and newborns from other data sources. RESULTS: Each year, around 185,000 pregnant women were screened for HIV, HBV and syphilis. Refusal rates for the screening tests were low, and were highest (0.2%) for HIV. The estimated annual prevalence of HIV among pregnant women was 0.05%.Prior to the introduction of screening, 5-10 children were born with HIV annually After the introduction of screening in 2004, only 4 children were born with HIV (an average of 1 per year). Two of these mothers had become pregnant prior to 2004; the third mother was HIV negative at screening and probably became infected after screening; the fourth mother's background was unknown. Congenital syphilis was diagnosed in fewer than 5 newborns annually and 5 children were infected with HBV. In 3 of these, the mothers were HBeAg positive (a marker for high infectivity). We estimated that 5-10 HIV, 50-75 HBV and 10 syphilis cases in newborns had been prevented annually as a result of screening. CONCLUSIONS: The screening programme was effective in detecting HIV, HBV and syphilis in pregnant women and in preventing transmission to the child. Since the introduction of the HIV screening the number of children born with HIV has fallen dramatically. PREVIOUS PUBLICATION: [Translation from: 'Prenatale screening op hiv, hepatitis B en syphilis in Nederland effectief', published in 'The Dutch Journal of Medicine ' (NTVG, in Dutch)].

The comparison of the performance of two screening strategies identifying newly-diagnosed HIV during pregnancy.

BACKGROUND: In the Netherlands, a non-selective opt-out instead of a selective opt-in antenatal HIV screening strategy was implemented in 2004. In case of infection, screening was followed by prevention of mother-to-child-transmission (PMTCT). We compared the performance of the two strategies in terms of detection of new cases of HIV and vertical transmission. METHODS: HIV-infected pregnant women were identified retrospectively from the Dutch HIV cohort ATHENA January 2000 to January 2008. Apart from demographic, virological and immunological data, the date of HIV infection in relation to the index pregnancy was established. Separately, all infants diagnosed with HIV born following implementation of the screening program were identified by a questionnaire via the paediatric HIV centres. RESULTS: 162/481 (33.7%) HIV-positive pregnant women were diagnosed with HIV before 2004 and 172/214 (80.3%) after January 2004. Multivariate analysis showed an 8-fold (95% confidence interval 5.47-11.87) increase in the odds of HIV detection during pregnancy after the national introduction of the opt-out strategy. Still, three children born during a 5-year period after July 2004 were infected due to de novo infection in pregnancy. CONCLUSIONS: Implementation of a nation-wide screening strategy based upon non-selective opt-out screening followed by effective PMTCT appeared to detect more HIV-infected women for the first time in pregnancy and to reduce vertical transmission of HIV substantially. Nonetheless, still few children are infected because of maternal infection after the first trimester. We propose the introduction of partner screening on HIV as part of the antenatal screening strategy.

Does physical activity in leisure time early in pregnancy reduce the incidence of preeclampsia or gestational hypertension?

OBJECTIVE: Assessment of the association of physical activity in leisure time with preeclampsia and gestational hypertension in nulliparous women. DESIGN: Population based prospective cohort study. SETTING: Amsterdam, The Netherlands. POPULATION: All pregnant women in Amsterdam between January 2003 and March 2004 who were nulliparous with a singleton pregnancy and who delivered after 24 weeks. DESIGN: At their first prenatal care visit, women were invited to fill out a questionnaire with sociodemographic and psychosocial variables. Physical activity in leisure time in the past week was measured using questions about walking, cycling, playing sports and other activities in leisure time. The amount of minutes and intensity of each activity was studied using four categories: no, low, moderate or high activity. By using multivariate logistic regression, we adjusted for sociodemographic and medical confounders. MAIN OUTCOME MEASURES: Incidence of preeclampsia and gestational hypertension. Results. A total of 12,377 women were invited with a response rate of 67%; 3,679 nulliparous women were included. The incidence of preeclampsia and gestational hypertension was 3.5% and 4.4%, respectively. The amount of time or intensity of physical activity in leisure time was not associated with a difference in risk of preeclampsia or gestational hypertension. CONCLUSION: Physical activity in leisure time early in pregnancy does not reduce the incidence of preeclampsia or gestational hypertension in an unselected population of nulliparous women.

Use of progesterone treatment for the prevention of recurrent preterm birth: identification of obstacles to change.

Progesterone treatment has proven to be effective in preventing recurrent preterm birth. The use of progesterone varies widely between different obstetric clinics in the Netherlands. The study aimed to identify factors that hamper or facilitate the use of progesterone to create an implementation strategy. A Web-based survey was developed containing questions on sociopolitical factors, organizational factors, knowledge, and attitude. This survey was spread among 212 gynecologists, 203 midwives, and 130 women with a recent preterm birth. Response rates were 46% for gynecologists, 57% for midwives, and 78% for patients. Twenty-five percent of gynecologists were prescribing progesterone, 21% of midwives would recommend progesterone, and 54% of patients were willing to undergo treatment in future pregnancies. Specific factors hampering implementation for gynecologists were working in nonteaching hospitals and absence of progesterone treatment in local protocols. For midwives and patients, unfamiliarity with progesterone was the most notable finding. The major reason for failure of implementation of progesterone treatment to prevent recurrent preterm birth is absence of this treatment in protocols and lack of familiarity with this treatment in midwives and patients. This may be overcome through adjustment of clinical protocols on regional and national levels.

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial.

BACKGROUND: 15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies. METHODS/DESIGN: We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16-20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length. DISCUSSION: This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40512715.

Sensitivity of spontaneous baroreflex control of the heart and hemodynamic parameters are not influenced by the menstrual cycle.

OBJECTIVE: The purpose of this study was to evaluate if hemodynamic parameters and sympathetic activity vary between the follicular and luteal phase of the menstrual cycle before using sympathetic activity in pre-pregnancy risk assessment for preeclampsia. METHODS: We studied 39 healthy women at days 5 to 10 and days 18 to 25 of the menstrual cycle. Blood pressure, heart rate, cardiac output, and total peripheral resistance were measured continuously using noninvasive finger arterial pressure waveform registration (Portapres Model 2, BMI, The Netherlands). Baroreflex sensitivity (BRS) and sympathetic activity by phase angle difference were studied using spectral analysis and xBRS. RESULTS: There were no differences in hemodynamic parameters, BRS, and phase angle difference. CONCLUSION: There is no difference in blood pressure, BRS, and sympathetic activity between the first and second half of the menstrual period. We recommend using the first half of the cycle to be certain that no pregnancy exists, as the influence of very early pregnancy is unknown.

Nelfinavir and nevirapine side effects during pregnancy.

BACKGROUND: The risk of vertical transmission of HIV has been substantially reduced since the introduction of highly active antiretroviral therapy (HAART); however, the impact of taking HAART during pregnancy on the woman, the fetus and the infant is not yet understood. OBJECTIVE: To assess and compare tolerability, safety and efficacy of nelfinavir- or nevirapine-containing HAART in a cohort of pregnant and non-pregnant HIV-infected women in The Netherlands. DESIGN: Retrospective comparative study. METHODS: In 15 centres specializing in HIV in The Netherlands, data on patient characteristics, HAART, adverse events, viral load response, mode of delivery and HIV status of the neonate were obtained from medical records of HIV-infected pregnant women who received HAART during pregnancy between January 1997 and June 2003. These data were compared with a control group of HIV-infected non-pregnant women that was obtained from the Dutch HIV-monitoring foundation database. RESULTS: Data from 186 pregnant and 186 non-pregnant HIV-infected women using a nelfinavir- or nevirapine-containing regimen were analysed. The pregnant women were younger, used a nelfinavir containing regimen more often, had higher CD4 cell counts and lower HIV RNA levels. Nelfinavir-related gastrointestinal symptoms (P < 0.001), hyperglycaemia (P < 0.001) and nevirapine-related hepatotoxicity (P = 0.003) occurred more often during pregnancy. The risk of nevirapine-induced rash was not increased. No major adverse events occurred. CONCLUSION: Nelfinavir- or nevirapine-containing HAART regimens during pregnancy are well tolerated. Side effects of antiretroviral therapy are more frequent in pregnant than in non-pregnant women.

Nelfinavir plasma concentrations are low during pregnancy.

Plasma nelfinavir concentration ratios (CRs) were calculated for all pregnant (n=27) and nonpregnant (n=48) human immunodeficiency virus type 1-infected women receiving the drug who visited our outpatient clinic. In pregnant women, mean and median nelfinavir CRs were significantly lower (P=.02 and P=.04, respectively), and 51% of the CRs were below the clinically relevant threshold of 0.90, compared with 35% of the CRs in nonpregnant women. After we adjusted for confounders, we found that the mean nelfinavir CR was 34% lower in pregnant women (P=.02). With targeted interventions, subsequent CRs in pregnant women showed a significant increase (median increase, 0.31; P=.01).

Enhanced coagulation activation in preeclampsia: the role of APC resistance, microparticles and other plasma constituents.

Coagulation activation in pregnancy is further enhanced in preeclampsia. We investigated whether this results from increased thrombin generation by the plasma itself or its cell-derived microparticles. Plasma samples were obtained from preeclamptic, normal pregnant and nonpregnant women (each n = 10). Prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) concentrations were increased in pregnancy and further increased in preeclampsia. In pregnancy and preeclampsia, increased activated protein C resistance occuffed (APC sensitivity ratio: 3.3 +/- 0.8 and 2.5 +/- 0.8, both P <0.001 vs. nonpregnant). In normal pregnant microparticle-free plasma the thrombin generation correlated with TAT (r = 0.84, P = 0.005) and APC resistance correlated with F1+2 (r = 0.68, P = 0.04). In preeclampsia thrombin generation by plasma was increased (P = 0.005), independent of APC resistance. Thrombin generation by microparticles was similar in all groups, although different coagulation activation pathways were utilized, indicating that circulating microparticles are not directly involved in coagulation activation in pregnancy and preeclampsia. In contrast, APC resistance can explain coagulation activation in pregnancy, while enhanced coagulation activation in preeclampsia results, in part, from an increased thrombin generating capacity of plasma independent of APC resistance.

Abnormal development of the vasculosyncytial membrane in early pregnancy failure.

OBJECTIVE: To investigate chorionic villous vasculogenesis (maturation) and development of the vasculosyncytial membrane (margination) using CD34 immunohistochemistry. DESIGN: Case-control study. SETTING: Microscopic analysis of first trimester chorionic villi. PATIENT(S): Twelve patients with anembryonic pregnancies, 12 with embryonic death, and 12 with terminated normal pregnancies. INTERVENTION(S): Quantitative analysis of chorionic villi blinded to group and gestational age using CD34 immunohistochemistry. MAIN OUTCOME MEASURE(S): Vascular parameters (mean functional vascular area, vessels with a lumen, and hemangiogenetic cords, peripherally or centrally located). RESULT(S): Terminated normal pregnancies show significantly more vessels per chorionic villus (maturation) (mean +/- SEM) in comparison with embryonic deaths and anembryonic pregnancies (5.3 +/- 0.3 vs. 1.4 +/- 0.2 and 0.7 +/- 0.1), located mainly peripherally (margination) (3.0 +/- 0.2 vs. 0.9 +/- 0.2 and 0.2 +/- 0.0). Anembryonic pregnancies show significantly more centrally located cords in comparison with embryonic deaths and termination of pregnancies (3.3 +/- 0.2 vs. 2.7 +/- 0.2 and 1.5 +/- 0.1). CONCLUSION(S): A defective chorionic villous vascularization, demonstrating inadequate vasculogenesis and abnormal development of the vasculosyncytial membrane, is seen in pregnancies complicated by embryonic death and is even more pronounced in anembryonic pregnancies. Initiation of placental vasculogenesis is a basic feature in all types of pregnancy and is subsequently modulated directly or indirectly by embryonic signaling.

Evaluation of suprascapular nerve neurotization after nerve graft or transfer in the treatment of brachial plexus traction lesions.

OBJECT: The aim of this retrospective study was to evaluate the restoration of shoulder function by means of suprascapular nerve neurotization in adult patients with proximal C-5 and C-6 lesions due to a severe brachial plexus traction injury. The primary goal of brachial plexus reconstructive surgery was to restore biceps muscle function and, secondarily, to reanimate shoulder function. METHODS: Suprascapular nerve neurotization was performed by grafting the C-5 nerve in 24 patients and by accessory or hypoglossal nerve transfer in 29 patients. Additional neurotization involving the axillary nerve was performed in 18 patients. Postoperative needle electromyography studies of the supraspinatus, infraspinatus, and deltoid muscles showed signs of reinnervation in most patients; however, active glenohumeral shoulder function recovery was poor. In nine (17%) of 53 patients supraspinatus muscle strength was Medical Research Council (MRC) Grade 3 or 4 and in four patients (8%) infraspinatus muscle power was MRC Grade 3 or 4. In 18 patients in whom deltoid muscle reinnervation was attempted, MRC Grade 3 or 4 function was demonstrated in two (11%). In the overall group, eight patients (15%) exhibited glenohumeral abduction with a mean of 44 +/- 17 degrees (standard deviation [SD]; median 45 degrees) and four patients (8%) exhibited glenohumeral exorotation with a mean of 48 +/- 24 degrees (SD; median 53 degrees). In only three patients (6%) were both functions regained. CONCLUSIONS: The reanimation of shoulder function in patients with proximal C-5 and C-6 brachial plexus traction injuries following suprascapular nerve neurotization is disappointingly low.

Trisomy 13 or 18 (mosaicism) in first trimester cytotrophoblast cells: false-positive results in 11 out of 51 cases.

OBJECTIVE: The finding of full or mosaic trisomy 13 or 18 in first trimester chorionic villus sampling (CVS) may be a false-positive result. This report provides incidence and outcome information that may be helpful in counselling individual patients and in choosing adequate follow-up. STUDY DESIGN: From a series of 6820 CVS cases, we retrospectively collected data on all patients (n=51) with full (n=30) or mosaic (n=5) trisomy 18, and full (n=13) or mosaic (n=3) trisomy 13 in cytotrophoblast cells. RESULTS: Five false-positives were seen in patients with full trisomy 18 and three in the mosaic cases. One false-positive result was observed in full trisomy 13 and two false-positives in cases of mosaicism. No false-negative results were reported. CONCLUSION: The diagnosis of trisomy 13 or 18 in cytotrophoblasts should be confirmed in other tissues, unless fetal abnormalities are seen at ultrasound. In case of mosaicism, follow-up amniocentesis is advised.

Fetal exposure to HIV-1 alters chemokine receptor expression by CD4+T cells and increases susceptibility to HIV-1.

Absolute numbers of lymphocytes are decreased in uninfected infants born to HIV-1-infected women (HIV-1-exposed). Although the exact mechanism is unknown, fetal exposure to maternal HIV-1-infection could prime the immune system and affect T cell trafficking. We compared the expression of chemokine receptors on cord blood CD4(+) T cells from HIV-1-exposed children and healthy controls. At baseline CD4(+) T cells had a largely naïve phenotype. However, stimulation with cytokines resulted in an upregulation of inflammatory response-related chemokine receptors on CD4(+) T cells, with HIV-1-exposed infants having a significantly higher frequency of CD4(+) T cells expressing, in particularly Th2 associated chemokine receptors (CCR3 p < 0.01, CCR8 p = 0.03). Numbers of naive CCR7(+) CD4(+) T cells were reduced (p = 0.01) in HIV-1-exposed infants. We further assessed whether the inflammatory phenotype was associated with susceptibility to HIV-1 and detected higher levels of p24 upon in in vitro infection of stimulated CD4(+) T cells of HIV-1-exposed infants. In summary, fetal exposure to HIV-1 primes the immune system in the infant leading to an enhanced immune activation and altered T cell homing, with potential ramifications regarding T cell responses and the acquisition of HIV-1 as an infant.

Complications of the 2009 influenza A/H1N1 pandemic in pregnant women in The Netherlands: a national cohort study.

The 2009 influenza A/H1N1 pandemic caused an increase in complications in pregnant women. To be well prepared for a next pandemic, we investigated the obstetric and maternal complications of this pandemic. In our national cohort of 59 pregnant women who were admitted to the hospital, no major complications apart from preterm birth and admission to the neonatal intensive care unit were observed. Although the small size of this study precludes us drawing any definitive conclusions, comparing our results with those in other countries suggests that the influenza A/H1N1 pandemic had a relatively benign course in pregnant women in The Netherlands.

Hcv coinfection, an important risk factor for hepatotoxicity in pregnant women starting antiretroviral therapy.

OBJECTIVES: This retrospective cohort study evaluated the risk of hepatotoxicity in HIV-1 positive pregnant and non-pregnant women starting combined ART. METHODS: Data were used from the ATHENA observational cohort. The study population consisted of HIV-1 infected, therapy naïve, pregnant and non-pregnant women, followed between January 1997 and February 2008. Demographic, treatment and pregnancy related data were collected. Risk of hepatotoxicity was determined using univariate and multivariate logistic regression. Analyses were adjusted for age, region of origin, baseline HIV-RNA levels and CD4 cell counts, cART regimen and hepatitis B and C coinfection. ALT and AST values of more than 5 times ULN were considered as hepatotoxicity. RESULTS: Four-hundred and twenty-five pregnant and 1121 non-pregnant women were included. Independent risk factors of hepatotoxicity in all women were the presence of detectable HCV RNA (OR 5.48, 95% CI 2.25-13.38, p<0.001) and NVP use (OR 2.63, 95% CI 1.54-4.55, p<0.001). Stratified for pregnancy, the adjusted risk of hepatotoxicity was significantly associated with HCV coinfection only during pregnancy (OR 23.53, 95% CI 4.69-118.01, p<0.001). NVP use is related to hepatotoxicity in pregnant (OR 5.26, 95% CI 1.61-16.67, p<0.005) as well as in non-pregnant women (OR 2.13, 95% CI 1.11-4.00, p=0.02). CONCLUSION: HCV coinfection and NVP use are associated with a higher risk of cART induced hepatotoxicity in pregnant women.