Altered strategy of prophylactic anti-D administration in pregnancy to cover term and post-term - a pilot study.

BACKGROUND AND OBJECTIVE: Routine antenatal anti-D prophylaxis (RAADP) to RhD-negative women is most often administered in gestational age (GA) 28-30 weeks with the next anti-D dose administered postpartum. The aim of this study was to analyse the proportion of RhD-negative women where RAADP is not detectable at term and in a pilot study to investigate whether RAADP administered in GA 28 and 38 results in detectable levels at term, post-term and post-delivery. MATERIALS AND METHODS: In a retrospective analysis, 4280 RhD-negative women carrying an RHD positive fetus were included and the proportion with a negative antibody screen at delivery was determined. In the second part, 39 pregnancies were included prospectively, a second dose of RAADP was administered in GA 38 weeks, and anti-D was quantified before the second dose and then weekly for 5 weeks. RESULTS: In the retrospective analysis, 20·5% (856/4280) with RAADP administered in GA 28 were negative in routine antibody screening at delivery. In the small prospective study, 18% (7/39) had a negative antibody screen and 26% (10/39) had levels below 0·005 IU/ml, in the quantification assay, in GA 38. Anti-D prophylaxis administered in GA 38 showed detectable levels of anti-D up to 30 days post-delivery, with concentration at delivery 0·060 ± 0·034 IU/ml (mean ± SD). CONCLUSION: Approximately 20% of the RhD-negative women show non-detectable levels of anti-D at term. A second dose of RAADP at GA 38 results in stable concentrations of anti-D at term, post-term and post-delivery, but with large interindividual variation.

Cerebrospinal fluid protein markers in PD patients after DBS-STN surgery-A retrospective analysis of patients that underwent surgery between 1993 and 2001.

OBJECTIVE: Cerebrospinal fluid (CSF) markers of neurodegeneration [neurofilament light chain (NFL), total Tau (T-Tau)], tau pathology [phosphorylated tau (p-Tau)], glial cell damage or activation [glial fibrillary acidic protein (GFAP)], and brain amyloidosis [ß-amyloid 1-42 (Aß42)] are useful for diagnosis and prognosis in several neurodegenerative disorders. In this paper we investigate these markers and their relationship to key clinical milestones in patients with advanced Parkinson´s disease (PD) operated at our center with subthalamic nucleus deep brain stimulation (STN-DBS) for at least 15 years ago. PATIENTS AND METHODS: Retrospective analysis of available cerebrospinal fluid and clinical data in PD-patients, 15 years or more after they underwent STN-DBS surgery. All PD-patients implanted with STN-DBS at Sahlgrenska University Hospital before January 1, 2001, were regularly assessed until January 10, 2018, or until death, or until lost to follow-up. RESULTS: Twenty three PD patients were operated with STN-DBS. Sixteen of these (six females and ten males) underwent at least one lumbar puncture (LP) immediately prior to or after STN-DBS. Their age at the latest available LP was 64 (55-75) years [median (range)], PD duration 20 (11-33) years, and Hoehn & Yahr (H&Y) stage 3 (2-4). Time between DBS operation and the last LP was 4.5 (0.3-10.8) years. Time from the last LP to the last follow up was 6 (0.1-18) years, and for the entire cohort 115 person-years. On January 10, 2018, four PD-patients (25%) were still alive. All preoperative CSF marker levels were normal. Between two days and six months after DBS, NFL and GFAP levels increased sharply but they normalized thereafter in most patients, and were normal up to almost 11 years after neurosurgery. Over time, all patients deteriorated slowly. At the last follow up, H&Y was 5 (3-5) and 12/16 were demented. There was no significant correlation between postoperative (> 6 months) CSF NFL, GFAP, T-Tau, p-Tau, ß-amyloid levels and the presence of dementia, psychosis, inability to walk or need for nursing home at the time for LP, nor for presence of dementia at the last follow up or for death as of January 10, 2018. CONCLUSION: CSF protein biomarkers remain normal despite long PD duration, severe disability, and chronic STN-DBS. They cannot be used for PD staging or prognostication but may indicate brain damage caused by other pathological factors.

Key clinical milestones 15 years and onwards after DBS-STN surgery-A retrospective analysis of patients that underwent surgery between 1993 and 2001.

OBJECTIVE: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for motor fluctuations in Parkinson's disease (PD), but does not halt disease progression. The long-term deterioration of key functions such as cognition, speech, ability to swallow, gait, urinary bladder control, orientation and reality perception is decisive for patients' independency in daily life. In this paper we investigated patients with advanced PD operated at our center with STN-DBS for at least 15 years ago, in respect to key clinical milestones reflecting their overall function in daily living. PATIENTS AND METHODS: Retrospective analysis of clinical data concerning key clinical milestones including death in PD-patients, 15 years or more after they underwent STN-DBS surgery. All PD-patients implanted with STN-DBS at Sahlgrenska Hospital before January 1, 2001, were regularly assessed until death, drop-out, or January 11, 2016. RESULTS: Sixteen men and seven women with a median (range) disease duration of 18 (10-28) years were operated with STN-DBS. The median (range) follow-up time post-surgery was 12 (2-18) years and 692 person-years of disease duration were observed. In January 2016, nine PD-patients (39%) were still alive (eight with active STN-DBS). Initially, motor symptoms improved in all patients. Sustained benefit (implying active stimulation at the last follow up) was maintained in 19 of them (83%) but STN-DBS was inactivated in four (17%) due to inefficacy. Over time, all patients deteriorated slowly, and a majority developed severe non-motor and axial symptoms such as dementia, inability to talk, swallow and walk, urinary incontinence, psychosis, and need for nursing home care. At the last follow up, 16/23 (70%) patients were treated with antidepressants. CONCLUSION: A majority of PD-patients experience sustained motor benefit with continuous STN-DBS. However, over time, non-motor and axial symptoms slowly and severely restrict PD-patients' function in their daily living.

Targeted routine antenatal anti-D prophylaxis in the prevention of RhD immunisation--outcome of a new antenatal screening and prevention program.

OBJECTIVE: To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP). MATERIALS AND METHODS: We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250-300 µg) was administered intramuscularly in gestational week 28-30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy. RESULTS: During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15-0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500. CONCLUSIONS: Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.

Pharmacokinetics of 250 µg anti-D IgG in the third trimester of pregnancy: an observational study.

OBJECTIVE: We present a pharmacokinetic study evaluating a single intramuscular dose of 250 µg anti-D immunoglobulin in the third trimester of pregnancy. The aim of the study was to determine the kinetic profile and duration of detectable levels of anti-D. DESIGN: Prospective observational study. SETTING: Antenatal outpatient clinic. POPULATION: Healthy Rhesus D (RhD)-negative pregnant women with an RHD-positive fetus. METHODS: Serial plasma anti-D quantitations following antenatal administration of anti-D immunoglobulin were performed using flow cytometry. Kinetic profiles for anti-D levels were generated from the concentration values at predetermined sampling time points. The half-lives were calculated by linear regression analysis. Main outcome measures. Time vs. concentration profile, half-life and anti-D concentration ≥1 ng/mL close to term. RESULTS: The maximal plasma concentration of anti-D was usually seen at 3-10 days postinjection, with a median value of 25 ng/mL. The half-life varied between individuals, with a median of 23 days. We found detectable levels of anti-D IgG within two weeks of parturition in 11 of 12 women. CONCLUSIONS: The preparation of anti-D immunoglobulin used in the present study, if administrated in pregnancy week 28-30, is associated with detectable levels of anti-D in most women at the time of delivery. Although the half-time is 23 days, it is uncertain whether all mothers have adequate anti-D concentrations at term. Alternative strategies may be evaluated in the future, with repeated administration of antenatal prophylaxis at term rather than conventional postpartum administration of anti-D.