Follow-up studies in prenatal medicine

With the availability of prenatal diagnostics in the last century, the fetus became a patient. Obstetricians looked togheter with neonatologist and pediatric surgeons, who in the past needed to treat sick neonates, for an earlier moment of treatment. An example of such a shift towards an earlier moment of treatment is the treatment of fetal tachycardia. Allready in utero medication can be given to the fetus transplacentally or direct fetally. In order to convert the tachycardia into a sinus rhythm. Another example is the anemic fetus who can be given an intrauterine blood transfusion to treat the anemia. A further example is the monochorionic twin with twin to twin transfusion syndrome. It is possible to coagulate the pathologic bloodvessel connections which cause the syndrome. Fetal death can be prevented by performing this procedure. A condition for the introduction of new techniques in medicine is that they are tested on efficacy and safety. That’s why new diagnostic and therapeutic procedures demand proper follow-up. Unwanted side effects, such as clubfeet after early amniocentesis, can be detected through careful and thorough follow-up before new techniques are applied on larger scale. Because follow-up research is needed after introduction of new techniques and because prognosis of the future child is very important for the expectant parents, we conducted the following studies. Chapter one comprehends the introduction of the thesis with a brief history of prenatal medicine. The introduction of new intrauterine treatment options increased possibilities. Not only can we timely diagnose abnormalities that cannot be treated (eg Down syndrome) but we can also diagnose diseases timely and treat abnormalities. Abnormalities that otherwise would lead to intrauterine fetal death (eg hydrops fetalis). Even performing intrauterine procedures that will increase a better start in life and therefore better starting point for postnatal treatment (eg prune belly syndrome). The importance of follow-up at infancy is on the one hand for the evaluation of new techniques, and on the other hand to inform parents adequately in case the fetus has an abnormality. Information on prognosis is important in making difficult decisions on either terminating the pregnancy, start intrauterine treatment or expectant management. Chapter two describes the annual results from all centers for invasive prenatal diagnosis in the Netherlands over the period 1991-2000, with particular emphasis on indications, abnormal results, type of invasive procedures, and terminations of pregnancy. The percentage of invasive prenatal diagnosis increased from 5% of births in 1991 to 6% in 1996 and subsequently remained level. During the study period, the number of pregnant women aged 36 and older increased by 70%, but the number of procedures because of maternal age remained stable. The percentage abnormal test results was 4.7 and increased from 3.6 in 1991 to 5.4 in 2000. The detection rate for abnormal results varied from 2% for maternal age to 28% for abnormalities detected by ultrasound examination. Important trends were the relative decrease of cordocentesis (-82%) and chorionic villi biopsy (-18%) in favour of amniocentesis. There was a significant decrease in the percentage of pregnant women aged 36 or older who underwent invasive prenatal diagnosis without previous screening. Chapter three represents de results of a (semi) randomized controlled study that compared the effects of transabdominal chorionic villus sampling and early amniocentesis on fetal mortality and child morbidity. Women requesting early prenatal diagnosis for advanced maternal age were allocated to early amniocentesis or transabdominal chorionic villus sampling either by randomization or, if they declined randomization, by their own choice. Of the 212 women who entered the study, 117 were randomized, 70 chose early amniocentesis and 25 chose transabdominal chorionic villus sampling. Overall, 130 women underwent early amniocentesis and 74 underwent transabdominal chorionic villus sampling at a median gestation of 12 weeks. Mosaic karyotypes were found in 5.4% of the early amniocenteses and in none of the chorionic villus samples. All unintended fetal losses occurred after early amniocentesis with a frequency of 6.2%. Talipes equinovarus was only observed after early amniocentesis with a frequency of 3.1%. The results of this study are in the Cochrane Database. In the nineties the early amniocentesis was abandonded because of the results of 3 controlled studies, including our study, that showed an increased risk of miscarriages and higher incidence of clubfeet. The conclusion of this chapter is that chorionic villus sampling remains the method of choice if prenatal diagnosis is needed in the first trimester of pregnancy. In chapter four the outcome of pregnancies with prenatally diagnosed central nervous system (CNS) malformations are described. Maternal and neonatal records of prenatally diagnosed CNS malformations were retrospectively reviewed over a 6-year period (1993–1998). Information on current development of surviving children was obtained by contacting the care-giving pediatric neurologist. During the study period 124 fetuses were diagnosed with a CNS malformation. Data on pregnancy and delivery were available for 118 pregnancies. Additional malformations were present in 47% of fetuses. A total of 46% of pregnancies were terminated, and 15% ended in spontaneous intrauterine death. A total of 39% of pregnancies resulted in live birth, and 25% of the infants were still alive at the age of 3 months. One child was lost to follow-up, one infant died at the age of 4 months, and two children died at the age of 3 years. Psychomotor development of the remaining 25 children was normal for 5, slightly disabled for 7, moderately disabled for 5 and severely disabled for 8. The conclusion of this chapter is that due to the high rate of termination of pregnancy and to the frequent association with other anomalies, the survival rate of pregnancies in which a CNS defect had been diagnosed prenatally was only 25%. More than 50% of surviving children were moderately or severely disabled. Chapter five decribes the neurodevelopmental assessment in children born with an umbilical artery pH < 7 in the period 1991-1992. During the study period, 1614 umbilical artery pH measurements were performed. Thirty (1.9%) were < 7. Of all infants born with an umbilical artery pH < 7 obstetric, neonatal, and pediatric records were reviewed. From this group 23 infants were admitted to the neonatal intensive care unit, and 8 of them required intubation. Twenty-eight children survived the neonatal period. At an age of 1 to 3 years, children were visited at home for semi-structured questioning of the mother and a Denver Developmental Screening Test of the child.Three children experienced an episode of mild hypertonia. One child had a mild motor developmental delay. The conclusion of this study is that babies born with an umbilical artery pH < 7 are at great risk to experience considerable short-term morbidity. Those who leave the neonatal intensive care unit without major problems have good outcomes, and pessimism in counselling their parents is unwarranted. Chapter six describes the long-term neurodevelopmental outcome in 33 children after twin-to-twin transfusion syndrome (TTTS). Maternal and neonatal medical records of all TTTS-cases admitted to our center between 1990 and 1998 were reviewed. Neurological and mental development at school age was assessed during a home visit in all TTTS-survivors. A total of 33 pregnancies with TTTS were identified. Four couples opted for termination of pregnancy. All other pregnancies were managed conservatively, 18 (62%) with serial amnioreductions and 11 (38%) without intrauterine interventions. Mean gestational age at delivery was 28 (range: 20-37) weeks. Perinatal mortality was 50% (29/58). Birth weight of donor twins was less than recipient twins. Systolic blood pressure at birth was lower in donors than in recipients and donors required more frequently inotropic support postnatally than recipients. The incidence of hypertension at birth was higher in recipients than in donors. Abnormal cranial ultrasonographic findings were reported in 41% (12/29) of the neonates. All long-term survivors (n = 29) were assessed during a home visit. Mean gestational age at birth of the surviving twins was 31 (range: 25-37) weeks. Mean age at follow-up was 6 (range: 4-11) years. The incidence of cerebral palsy was 21% (6/29). Five out of six children with cerebral palsy had an abnormal mental development. The incidence of cerebral palsy in the group of survivors treated with serial amnioreduction was 26% (5/19). Four children were born after intrauterine fetal death of their co-twin: two of them had cerebral palsy. The conclusion therefore is: the incidence of adverse neurodevelopmental outcome in TTTS-survivors is high, especially after intrauterine fetal death of a co-twin. In chapter seven the long-term neurodevelopmental status of children treated with intrauterine red blood cell and platelet transfusion (IUT) for fetal hydrops caused by parvovirus B19 infection is described. Maternal and neonatal records of all intrauterine transfusions for congenital parvovirus B19 infection in our center between 1997 - 2005 were reviewed. A total of 25 IUT sessions were performed in 24 hydropic fetuses. Sixteen survivors aged 6 months to 8 years were included in the follow-up study. All children underwent a general pediatric, a neurological examination and a neurodevelopment examination (developmental index by Bayley Scales of Infant Development or Snijders-Oomen test). Eleven children (68%) were normal and 5 children (32%) demonstrated a delayed psychomotor development with a suboptimal neurological examination (mild delay n=3, severe delay n=2). Neurodevelopmental status did not correlate with pre-IUT hemoglobin, platelet, or blood pH values. Growth and general health status were normal in all. Two children had minor congenital defects. Neurodevelopmental status was abnormal in 5 out of 16 survivors and was not related with the severity of fetal anemia and acidemia. We hypothesize that fetal parvovirus B19 infection may induce central nervous system damage. Chapter eight describes the results of a retrospective cohort study of children with fetal arrhythmia. In the Leiden University Medical Center, 44 fetuses were diagnosed with fetal cardiac arrhythmia between January 1990 and December 2005. Twenty-eight with supravenricular tachycardia (SVT), 7 with atrial flutter (AF) and 9 with atrioventricular block (AVB). The incidence of cardiac anomalies was 18%. Hydrops was seen in 42-50%. Direct or transplacental fetal antiarrhythmic medication was given in 76% of cases. In the SVT group, 19 children needed medication postpartum. In 16/19 infants, the arrhythmia ceased within the first year of life. In the SVT and AF group mortality was 6%. In 21% of these cases Wolff Parkinson White (WPW) syndrome was diagnosed. Mental scores were normal in all survivors. Of the seven cases of AVB included in the follow-up there is no survivor. The other two cases were lost for long-term follow-up, but their medical records noted pacemaker therapy in one and severe mental retardation in the other. In conclusion, mortality in SVT and AF patients in our study was 6% but mental scores were normal in all survivors. Twenty-one per cent of survivors had WPW syndrome. Prognosis in AVB patients was poor. Chapter nine comprehends the general discussion. We look into the demands of follow-up after prenatal diagnosis and therapy. How does loss to follow-up influence outcome? What is the best age to test for follow-up? Which test to use. After prenatal therapy, follow-up should always be performed as a standard procedure. Follow-up needs to comprehend the review of the medical records, specific testing and standard neurologic and developmental tests. An example of a good test, and age of testing is to perform a Bayley Scale of Infant Development test at the age of 2 with neurologic testing (e.g. Touwen). At the age of 5-6 years a further examination can be performed. Follow-up at a later age looks less sensible because postnatal factors influence outcome and prenatal techniques are developing continuously.</table

Alterations in classical and nonclassical HLA expression in recurrent and progressive HPV-induced usual vulvar intraepithelial neoplasia and implications for immunotherapy

TI9 - Endometriumpathologi

Immediate versus delayed removal of urinary catheter after laparoscopic hysterectomy: A randomised controlled trial

Objective: To evaluate if immediate catheter removal (ICR) after laparoscopic hysterectomy is associated with similar retention outcomes compared with delayed removal (DCR). Study design: Non-inferiority randomised controlled trial. Population: Women undergoing laparoscopic hysterectomy in six hospitals in the Netherlands. Methods: Women were randomised to ICR or DCR (between 18 and 24 hours after surgery). Primary outcome: The inability to void within 6 hours after catheter removal. Results: One hundred and fifty-five women were randomised to ICR (n = 74) and DCR (n = 81). The intention-to-treat and per-protocol analysis could not demonstrate the non-inferiority of ICR: ten women with ICR could not urinate spontaneously within 6 hours compared with none in the delayed group (risk difference 13.5%, 5.6–24.8, P = 0.88). However, seven of these women could void spontaneously within 9 hours without additional intervention. Regarding the secondary outcomes, eight women from the delayed group requested earlier catheter removal because of complaints (9.9%). Three women with ICR (4.1%) had a urinary tract infection postoperatively versus eight with DCR (9.9%, risk difference −5.8%, −15.1 to 3.5, P = 0.215). Women with ICR mobilised significantly earlier (5.7 hours, 0.8–23.3 versus 21.0 hours, 1.4–29.9; P ≤ 0.001). Conclusion: The non-inferiority of ICR could not be demonstrated in terms of urinary retention 6 hours after procedure. However, 70% of the women with voiding difficulties could void spontaneously within 9 hours after laparoscopic hysterectomy. It is therefore questionable if all observed urinary retention cases were clinically relevant. As a result, the clinical advantages of ICR may still outweigh the risk of bladder retention and it should therefore be considered after uncomplicated laparoscopic hysterectomy. Tweetable abstract: The advantages of immediate catheter removal after laparoscopic hysterectomy seem to outweigh the risk of bladder retention.Medical Instruments & Bio-Inspired Technolog

Impact of the COVID-19-pandemic on patients with gynecological malignancies undergoing surgery: A Dutch population-based study using data from the 'Dutch Gynecological Oncology Audit'

Objective. The COVID-19-pandemic caused drastic healthcare changes worldwide. To date, the impact of these changes on gynecological cancer healthcare is relatively unknown. This study aimed to assess the impact of the COVID-19-pandemic on surgical gynecological-oncology healthcare.Methods. This population-based cohort study included all surgical procedures with curative intent for gynecological malignancies, registered in the Dutch Gynecological Oncology Audit, in 2018-2020. Four periods were identified based on COVID-19 hospital admission rates: 'Pre-COVID-19', 'Firstwave', 'Interimperiod', and'Second wave'. Surgical volume, perioperative care processes, and postoperative outcomes from 2020 were compared with 2018-2019.Results. A total of 11,488 surgical procedureswere analyzed. For cervical cancer, surgical volume decreased by 17.2% in 2020 compared to 2018-2019 (mean 2018-2019: n= 542.5, 2020: n= 449). At nadir (interimperiod), only 51% of the expected cervical cancer procedures were performed. For ovarian, vulvar, and endometrial cancer, volumes remained stable. Patients with advanced-stage ovarian cancer more frequently received neoadjuvant chemotherapy in 2020 compared to 2018-2019 (67.7% (n = 432) vs. 61.8% (n = 783), p = 0.011). Median time to first treatmentwas significantly shorter in all four malignancies in 2020. For vulvar and endometrial cancer, the length of hospital staywas significantly shorter in 2020. No significant differences in complicated course and 30-day-mortality were observed.Conclusions. The COVID-19-pandemic impacted surgical gynecological-oncology healthcare: in 2020, surgical volume for cervical cancer dropped considerably, waiting time was significantly shorter for all malignancies, while neoadjuvant chemotherapy administration for advanced-stage ovarian cancer increased. The safety of perioperative healthcare was not negatively impacted by the pandemic, as complications and 30-day-mortality remained stable. (C) 2022 The Authors. Published by Elsevier Inc.Analysis and support of clinical decision makin

Clinical auditing as an instrument to improve care for patients with ovarian cancer: The Dutch Gynecological Oncology Audit (DGOA)

Introduction: The Dutch Gynecological Oncology Audit (DGOA) was initiated in 2014 to serve as a nationwide audit, which registers the four most prevalent gynecological malignancies. This study presents the first results of clinical auditing for ovarian cancer in the Netherlands. Methods: The Dutch Gynecological Oncology Audit is facilitated by the Dutch Institute of Clinical Auditing (DICA) an