Re-emergence of pertussis despite high vaccination coverage in western countries, results in increased risk for severe and even fatal pertussis among newborns. For this reason, late 2015 the Dutch Health Council (HC) advised to offer 3rd trimester pertussis vaccination to pregnant women. At the start of the maternal pertussis programme late 2019, the maternal Tdap was advised from 22w of gestation onwards. Preterms, accounting for 8% of newborns in the Netherlands, are at highest risk for severe pertussis leading to prolonged hospital and intensive care admissions and sometimes death. Recently, it has become evident that despite 3rd trimester vaccination, preterms remain at high risk because the vaccination is likely given too late for sufficient antibody transfer. For this vulnerable group 2nd trimester vaccination may offer better protection because of extended time for antibody transfer. To date, most countries recommend 3rd trimester vaccination to protect young, not yet (fully) vaccinated infants. Data from England show 91% effectiveness against infant pertussis after maternal Tetanus- diphtheria -acellular Pertussis (Tdap) vaccination in the 3rd trimester. Studies focussing on preterms and protection after maternal vaccination are scarce. Two observational studies reported on effectiveness and antibody levels in cord blood of 2nd trimester vaccination in term infants. While one study showed significantly higher antibody levels after 2nd trimester vaccination (13-25 gestational weeks; GW), another study showed decreased effectiveness of 2nd trimester (<27 GW) vaccination. Only one study concerned antibody transfer in preterms and reported higher antibody levels after 2nd (n=37) than after 3rd (n=48) trimester vaccination. Aiming to contribute to setting optimal vaccine strategy of maternal pertussis vaccination in the Netherlands and elsewhere and particular for the most vulnerable group of preterms, we propose a study that compares pertussis antibody levels in preterms and terms after 2nd trimester maternal vaccination. We can compare these to data we have on 3rd trimester Tdap in terms. In addition to adequate antibody levels, success of 2nd trimester vaccination depends on acceptance of this strategy by pregnant women and professionals. Our primary endpoint is IgG anti-pertussis toxin (Pt) antibody concentration in preterms and terms at 2m of age, Pt is considered the most relevant antibody for protection against clinical pertussis. Secondary endpoints are e.g. pertussis specific antibody concentrations in preterms and terms in cord blood and in women at delivery. Determinants of acceptance of 2nd trimester maternal vaccination are also a secondary endpoint. Antibody concentrations will be assessed in serum, using a fluorescent bead-based multiplex immunoassay, with required blood volume of minimal 100µl. For the survey on acceptance, we aim to have 4 groups of 100 women each, i.e. women who are pregnant for the 1st time, women who already gave birth and in both groups women with and without a known increased risk of preterm delivery. For the immunogenicity part, we aim to have at least 60 preterms and 60 terms, as this is, according to experts, the minimum number to enable good comparisons. Pregnant women will be offered 2nd trimester pertussis vaccination. Both among acceptors and non-acceptors acceptance of 2nd trimester vaccination will be assessed. Women are first asked to participate in the acceptance part after the 1st antenatal visit to a midwife or obstetrician. They fill in a questionnaire to assess behavioral determinants and beliefs that underlie acceptance of 2nd trimester maternal vaccination. Only after this consent, women will be asked to participate in the immunogenicity part. Hereby, women will receive Tdap after they have the 20w standard anomaly ultrasound scan (20-24 GW). Vaccinated women will be followed until delivery. All preterms and a random selection of 60 terms, all of vaccinated mothers, will be followed until 2m of age, i.e. just before start of the NIP. By including both women in primary and secondary antenatal care, we aim to enrich our study population with women who are at increased risk for preterm delivery, as these women are usually seen by an obstetrician. Data from our study will determine whether 2nd trimester Tdap leads to sufficient Pt antibodiy concentration in terms and preterms compared to 3rd trimester vaccination. Furthermore, we will have knowledge about obstacles for acceptance and can tailor information for all pregnant women to overcome these. Finally, given that in near future besides pertussis other maternal vaccines are likely to become available for prevention of severe disease in newborns (RSV, GBS), in particular in preterms, this study generates essential knowledge for future vaccine policy of maternal vaccines.

Genexpressie in muizen om invloed van vasten te bepalen op nierschade door ischemia-reperfusie bij operatie. Dit is gedaan in jonge slanke en oude obese muizen.

Genexpressie in longen van volwassen en oude muizen na infectie met RSV

Genexpressie in lever van twee muismodellen na blootstelling aan benzo(a)pyreen; normale WT en DNA repair deficiente Xpa-/-p53+/- muizen.

genexpressie in stamcellen na blootstelling aan verschillende concentraties flusilazol

Genexpressie in geïsoleerde levercellen van twee muismodellen na blootstelling aan benzo(a)pyreen; normale WT en DNA repair deficiente Xpa-/-p53+/- muizen.

Genexpressie in bloed en lymfeknopen van muizen na infectie met RSV

Genexpressie effecten in muizenlever bij steatose door blootstelling aan amiodaron, valproïnezuur en tetracycline

Genexpressie effecten in zebravisembryos door blootstelling aan 14 stoffen

genexpressie in humane neurale stamcellen na blootstelling aan stoffen