J. M. Koelewijn

Effect of screening for red cell antibodies, other than anti‐D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first‐trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti‐D was evaluated.

One single dose of 200 μg of antenatal RhIG halves the risk of anti-D immunization and hemolytic disease of the fetus and newborn in the next pregnancy

BACKGROUND: The objective was the evaluation of the effect of the Dutch national routine antenatal RhIG (anti‐D) immunization prevention (RAADP) program comprising one single dose of 200 μg (1000 IU) of RhIG in the 30th week of pregnancy, restricted to women without a living child.

Haemolytic disease of the fetus and newborn.

Haemolytic Disease of the Fetus and Newborn (HDFN) is caused by maternal alloimmunization against red blood cell antigens. In severe cases, HDFN may lead to fetal anaemia with a risk for fetal death and to severe forms of neonatal hyperbilirubinaemia with a risk for kernicterus. Most severe cases are caused by anti‐D, despite the introduction of antental and postnatal anti‐D immunoglobulin prophylaxis. In general, red blood cell antibody screening programmes are aimed to detect maternal alloimmunization early in pregnancy to facilitate the identification of high‐risk cases to timely start antenatal and postnatal treatment. In this review, an overview of the clinical relevance of red cell alloantibodies in relation to occurrence of HDFN and recent views on prevention, screening and treatment options of HDFN are provided.

Risk factors for the presence of non-rhesus D red blood cell antibodies in pregnancy.

Objective  To identify risk factors for the presence of non‐rhesus D (RhD) red blood cell (RBC) antibodies in pregnancy. To generate evidence for subgroup RBC antibody screening and for primary prevention by extended matching of transfusions in women <45 years.

Risk factors for RhD immunisation despite antenatal and postnatal anti‐D prophylaxis

Objective To identify risk factors for Rhesus D (RhD) immunisation in pregnancy, despite adequate antenatal and postnatal anti‐D prophylaxis in the previous pregnancy. To generate evidence for improved primary prevention by extra administration of anti‐D Ig in the presence of a risk factor.

Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia

Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life‐threatening disease where fetal platelets are destroyed by maternal anti‐platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. We recently found IgG Fc‐glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core‐fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. Here we analysed the N‐linked glycans of human platelet antigen (HPA)‐1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). Besides a significant decrease in Fc‐fucosylation after the first pregnancy (P = 0·0124), Fc‐glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. Multiple logistic regression analysis identified anti‐HPA‐1a –fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT.

Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn

Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti‐RBC IgG alloantibodies. HDFN is most often caused by anti‐D but may also occur due to anti‐K, ‐c‐ or ‐E. We recently found N‐linked glycosylation of anti‐D to be skewed towards low fucosylation, thereby increasing the affinity to IgG‐Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. Here, we analysed 230 pregnant women with anti‐c, ‐E or –K alloantibodies from a prospective screening cohort and investigated the type of Fc‐tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. Anti‐c, ‐E and –K show – independent of the event that had led to immunisation – a different kind of Fc‐glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti‐D. High Fc‐galactosylation and sialylation of anti‐c correlated with HDFN disease severity, while low anti‐K Fc‐fucosylation correlated with severe fetal anaemia. IgG‐Fc glycosylation of anti‐RBC antibodies is shaped depending on the antigen. These features influence their clinical potency and may therefore be used to predict severity and identify those needing treatment.

Assessing psychological health in midwifery practice: A validation study of the Four-Dimensional Symptom Questionnaire (4DSQ), a Dutch primary care instrument

OBJECTIVE the Four-Dimensional Symptom Questionnaire (4DSQ) is a validated self-report questionnaire, developed for general practice to assess the level of distress, somatization, depression and anxiety among patients. This study evaluated the validity of this instrument for midwifery practice by differential item functioning analysis. DESIGN cross-sectional. SETTING AND PARTICIPANTS the focal group consisted of clients of 15 primary care midwifery practices in The Netherlands (n=478). The reference group consisted of Dutch female primary care patients, matched for age (n=478). MEASUREMENTS AND FINDINGS Differential item functioning (DIF) was assessed by ordinal regression and the Mantel Haenszel method. The impact of DIF was measured by linear regression. The depression scale was free of DIF. The somatization, distress and anxiety scale contained items with DIF. Because of DIF, pregnant and postpartum women had on average 1-2 points lower predicted scores on the somatization scale and 1 point lower scores on the anxiety scale. On the distress scale the midwifery group had 1-2 higher predicted scores. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE the 4DSQ is a valid instrument for casefinding of psychological disease in midwifery practice, provided cut-off scores of the distress, anxiety and somatization scale be adapted.

Women's attitude towards prenatal screening for red blood cell antibodies, other than RhD

BackgroundSince July 1998 all Dutch women (± 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for benefits, consequences and costs of screening for non-RhD antibodies is still under discussion. The screening program was evaluated in a nation-wide study. As a part of this evaluation study we investigated, according to the sixth criterium of Wilson and Jüngner, the acceptance by pregnant women of the screening program for non-RhD antibodies.MethodsControlled longitudinal survey, including a prenatal and a postnatal measurement by structured questionnaires. Main outcome measures: information satisfaction, anxiety during the screening process (a.o. STAI state inventory and specific questionnaire modules), overall attitude on the screening program. Univariate analysis was followed by standard multivariate analysis to identify significant predictors of the outcome measures. Participants: 233 pregnant women, distributed over five groups, according to the screening result.ResultsSatisfaction about the provided information was moderate in all groups. All screen- positive groups desired more supportive information. Anxiety increased in screen- positives during the screening process, but decreased to basic levels postnatally. All groups showed a strongly positive balance between perceived utility and burden of the screening program, independent on test results or background characteristics.ConclusionWomen highly accept the non-RhD antibody screening program. However, satisfaction about provided information is moderate. Oral and written information should be provided by obstetric care workers themselves, especially to screen-positive women.

Better perineal outcomes in sitting birthing position cannot be explained by changing from upright to supine position for performing an episiotomy

BACKGROUND women who give birth in supine position are more likely to have an episiotomy than women who give birth in sitting position. A confounding effect may be that women in upright positions in second stage of labour are asked to lie down if a professional needs to perform an episiotomy. This prospective cohort study aimed to determine whether this factor can explain the lower rate of episiotomy in sitting compared to supine position. METHODS data from 1196 women who had a spontaneous, vaginal birth were analysed. Positions during second stage and at birth were carefully recorded. Three groups of birthing positions were compared in multivariable analyses: 1) horizontal during second stage and supine at birth (horizontal/supine), 2) horizontal and upright during second stage and supine at birth (various/supine), 3) sitting at birth regardless of the position in second stage. Logistic regression analysis was used to adjust for known risk factors for perineal damage. FINDINGS women in sitting position at birth compared to those in the horizontal/supine group had a lower episiotomy rate (adjusted OR 0.28;95%-CI 0.14-0.56) and a non-significant higher intact perineum rate (adjusted OR 1.40, 95% CI 0.96-2.04). Women in the various/supine group compared to the horizontal/supine group had a similar episiotomy rate (adjusted OR 1.12;95%-CI 0.69-1.83). CONCLUSIONS we did not confirm our hypothesis that more women in supine compared to sitting position have an episiotomy because women in upright position are asked to lie down if an episiotomy is necessary.