Following targeted routine antenatal anti-D prophylaxis, almost half of the pregnant women had undetectable anti-D prophylaxis at delivery.

INTRODUCTION: In September 2016, a nationwide targeted routine antenatal anti-D prophylaxis program was implemented in Norway. The prophylaxis (anti-D immunoglobulin) aims to cover the whole third trimester and is administered in gestational week 28 to RhD-negative women who carry RhD-positive fetuses. However, in many women, antibody screening at delivery does not detect anti-D immunoglobulin. The goal of this study was to investigate the presumable role of dose and timing of antenatal anti-D immunoglobulin administration in non-detectable prophylaxis at the time of delivery. MATERIAL AND METHODS: In this retrospective observational study, RhD-negative pregnant women who gave birth at Oslo University Hospital and Akershus University Hospital between January 2017 and December 2019 were analyzed. Women who received antenatal anti-D immunoglobulin (1500 IU at Oslo University Hospital and 1250 IU at Akershus University Hospital) when fetal RHD genotyping at gestational week 24 predicted an RhD-positive fetus were included if an antibody screen at delivery was available. Data from the blood bank, maternity information systems, and electronic patient records were used. RESULTS: Analysis of the 984 RhD-negative women at the two hospitals revealed that 45.4% had non-detectable anti-D at delivery. A significant difference between the two hospitals was observed: 40.5% at Oslo University Hospital (n = 509) and 50.7% at Akershus University Hospital (n = 475) (p = 0.001). The proportion with non-detectable anti-D increased to 56.0 and 75.3%, respectively (p = 0.008) in the group of women who gave birth 12 weeks after routine antenatal anti-D prophylaxis. Significantly fewer women had detectable anti-D at delivery when the lower anti-D immunoglobulin dose (1250 IU) was administered antenatally. Multiple logistic regression indicated that the time interval between routine antenatal anti-D prophylaxis and delivery, in addition to anti-D dose, were significantly associated with detectable anti-D at delivery (p < 0.001). CONCLUSIONS: We do not know which RhD-negative pregnant women, despite antenatal anti-D prophylaxis, are at risk of RhD alloimmunization, when antibody screening is negative at delivery. Administration of antenatal prophylaxis should probably be moved closer to delivery, since the risk of fetomaternal hemorrhage is higher during the last weeks of the third trimester.

Matrix metalloproteinase-9 activity increased by two different types of epileptic seizures that do not induce neuronal death: a possible role in homeostatic synaptic plasticity.

Matrix metalloproteases (MMPs) degrade or modify extracellular matrix or membrane-bound proteins in the brain. MMP-2 and MMP-9 are activated by treatments that result in a sustained neuronal depolarization and are thought to contribute to neuronal death and structural remodeling. At the synapse, MMP actions on extracellular proteins contribute to changes in synaptic efficacy during learning paradigms. They are also activated during epileptic seizures, and MMP-9 has been associated with the establishment of aberrant synaptic connections after neuronal death induced by kainate treatment. It remains unclear whether MMPs are activated by epileptic activities that do not induce cell death. Here we examine this point in two animal models of epilepsy that do not involve extensive cell damage. We detected an elevation of MMP-9 enzymatic activity in cortical regions of secondary generalization after focal seizures induced by 4-aminopyridine (4-AP) application in rats. Pro-MMP-9 levels were also higher in Wistar Glaxo Rijswijk (WAG/Rij) rats, a genetic model of generalized absence epilepsy, than they were in Sprague-Dawley rats, and this elevation was correlated with diurnally occurring spike-wave-discharges in WAG/Rij rats. The increased enzymatic activity of MMP-9 in these two different epilepsy models is associated with synchronized neuronal activity that does not induce widespread cell death. In these epilepsy models MMP-9 induction may therefore be associated with functions such as homeostatic synaptic plasticity rather than neuronal death.