Susanna Sainio

Preterm delivery after surgical treatment for cervical intraepithelial neoplasia.

OBJECTIVE: To study whether a treatment of cervical intraepithelial neoplasia (CIN) is associated with an adverse outcome in the subsequent pregnancies. METHODS: This study is a register-based retrospective cohort study from Finland. National data of 25,827 women having a surgical treatment of the cervix for CIN in 1986–2003 and their 8,210 subsequent singleton births in 1987–2004 were studied. Main outcome measures were preterm birth rate, low birth weight rate, and perinatal mortality rate. RESULTS: The risk of any preterm delivery (less than 37 weeks of gestation), especially the risk of very preterm delivery (28–31 weeks of gestation), and extremely preterm delivery (less than 28 weeks of gestation) was increased after cervical conization (relative risk [RR] 1.99, 95% confidence interval [CI] 1.81–2.20; RR 2.86, 95% CI 2.22–3.70; and RR 2.10, 95% CI 1.47–2.99, respectively). After cervical ablation, the risk of preterm delivery was also increased. The risk of low birth weight and perinatal death was increased after conization (RR 2.06, 95% CI 1.83–2.31 and RR 1.74, 95% CI 1.30–2.32, respectively). Adjusting for maternal age, parity, and maternal smoking did not affect our results. CONCLUSION: Any treatment for CIN, including loop electrosurgical excision procedure, increases the risk of preterm delivery. It is important to emphasize this when treating young women with CIN. LEVEL OF EVIDENCE: II

Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry

Objective To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset. Design Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001–2010. Setting 13 tertiary referral centres from nine countries across the world. Participants 37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed. Primary and secondary outcome measures Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures. Results From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH. Conclusions ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester.

Associations of maternal age with maternity care use and birth outcomes in primiparous women: a comparison of results in 1991 and 2008 in Finland

To compare birth outcomes and maternity care use in 1991 and 2008 by age among primiparous Finnish women.

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.

At what age does the risk for adverse maternal and infant outcomes increase? Nationwide register-based study on first births in Finland in 2005–2014

It is poorly understood if there are specific ages at which adverse outcomes during pregnancy and childbirth start to increase (threshold‐ages). The purpose of this study was to examine at which maternal ages the use of maternity care and the risks for adverse maternal and infant outcomes increase.

Usefulness of maternal anti-HPA-1a antibody quantitation in predicting severity of foetomaternal alloimmune thrombocytopenia

To study the clinical usefulness of maternal anti‐HPA‐1a antibody levels in predicting severe foetomaternal alloimmune thrombocytopenia (FMAIT).

Diagnosis and treatment of severe hemolytic disease of the fetus and newborn: a 10-year nationwide retrospective study.

Outcome after intrauterine transfusions due to severe hemolytic disease of the fetus and newborn.

Targeted antenatal anti‐D prophylaxis program for RhD‐negative pregnant women – outcome of the first two years of a national program in Finland

The aim of this study was to assess the accuracy of the non‐invasive fetal RHD test at 24–26 weeks of gestation as part of the national antenatal screening program to target routine antenatal anti‐D prophylaxis (RAADP) at 28–30 weeks at women carrying an RhD‐positive fetus.

Maternal HLA genotyping is not useful for predicting severity of fetal and neonatal alloimmune thrombocytopenia

Lack of reliable laboratory parameters is the main challenge in the management of fetal and neonatal alloimmune thrombocytopenia (FNAIT). Despite the long‐known association between the HLA‐DRB3*01:01 allele and human platelet antigen 1a (HPA‐1a) alloimmunisation, maternal human leucocyte antigen (HLA) typing has been of little clinical value. Recently, other DRB3 allele variants have been suggested to predict the severity of FNAIT. In this nationwide population‐based retrospective cohort study, we performed extensive HLA typing of 96 women, accounting for 87% of our cohort of 110 families with confirmed or possible HPA‐1a‐immunisation. The HLA type was compared with anti‐HPA‐1a levels, severity of neonatal disease and responsiveness to maternally administrated intravenous gammaglobulin (IVIG). HLA haplotypes were constructed to investigate further HLA associations. Despite significantly lower anti‐HPA‐1a levels in DRB3*01:01‐negative women, the carrier status of this particular allele could not be used to confirm or rule out FNAIT in the absence of detectable antibodies. In the haplotype analysis, the DRB3*01:01 allele was the actual factor associated with FNAIT. No other HLA allele was shown to be of additional value as a predictor of severe FNAIT or non‐responsiveness to IVIG treatment. Thus, HLA genotyping was not found useful in differentiating high‐ and low‐risk pregnancies or in guiding antenatal treatment in affected families.