Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Total pregnancy loss after chorionic villus sampling and amniocentesis: a cohort study.

OBJECTIVES: To identify maternal-, operator- and procedure-related variables that affect procedure-related pregnancy loss after transcervical (TC) and transabdominal (TA) chorionic villus sampling (CVS) and amniocentesis and to estimate the rates of spontaneous and procedure-related loss in comparable subgroups of women. METHODS: This was a retrospective cohort study conducted at the University Medical Center Groningen and the Academic Medical Center, The Netherlands. Databases of both centers were searched to identify singleton pregnancies that had undergone a combined test and/or anomaly scan at around 20 weeks' gestation, or an invasive procedure (CVS and/or amniocentesis) between January 2001 and December 2011. Maternal characteristics, obstetric history, technical aspects of the invasive procedure, ultrasound examinations and fetal and neonatal outcomes were available for 29 201 cases. Women were categorized, according to the type of examination they had received, into the following five groups: first-trimester combined test (and 20-week anomaly scan); 20-week anomaly scan only; CVS; amniocentesis; amniocentesis after unsuccessful CVS. Rates of fetal loss were compared between groups. RESULTS: Variables significantly associated with a higher rate of fetal loss were, for CVS, repeat attempts during the procedure, use of TC cannula instead of biopsy forceps, gestational age at procedure ≥ 13 weeks and a pregnancy after assisted reproductive techniques, and, for amniocentesis, if indication was fetal anomaly or family history of anomalies and repeat attempts during the procedure. In women aged ≥ 36 years who did not undergo an invasive procedure, spontaneous fetal loss rate (FLR) after first-trimester combined test was 1.40%, whereas after CVS, FLR was 2.76% and 2.43% for a TC and TA approach, respectively. The additional risk of fetal loss with TC-CVS was therefore 1.36% (1 : 74), which varied according to the instrument used (0.27% for forceps and 3.12% for cannula), and with TA-CVS was 1.03% (1 : 97). In women aged ≥ 36 years who underwent a 20-week anomaly scan only, spontaneous FLR was 0.63%. In women who underwent amniocentesis solely because of advanced maternal age, FLR was 1.11%. The additional risk of fetal loss with amniocentesis was 0.48% (1 : 208). CONCLUSION: The total rate of procedure-related fetal loss after TA- and TC-CVS and amniocentesis appears lower than the risks on which women are currently counseled. There was a trend for a decrease in risk when the level of experience of the operator increased. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Risk stratification for healthcare planning in women with gestational diabetes mellitus.

BACKGROUND: To identify relevant factors predicting the need for insulin therapy in women with gestational diabetes mellitus (GDM) and secondly to determine a potential 'low- risk' diet-treated group who are likely to have good pregnancy outcomes. METHODS: A retrospective analysis between 2011-2014. Multivariable backward stepwise logistic regression was used to identify the predictors of the need for insulin therapy. To identify a 'low-risk' diet-treated group, the group was stratified according to pregnancy complications. Diet-treated women with indications for induction in secondary care were excluded. RESULTS: A total of 820 GDM women were included, 360 (44%) women required additional insulin therapy. The factors predicting the need for insulin therapy were: previous GDM, family history of diabetes, a previous infant weighing ≥ 4500 gram, Middle-East/North-African descent, multiparity, pre-gestational BMI ≥ 30 kg/m2, and an increased fasting glucose level ≥ 5.5 mmol/l (OR 6.03;CI 3.56-10.22) and two-hour glucose level ≥ 9.4 mmol/l after a 75-gram oral glucose tolerance test at GDM diagnosis. In total 125 (54%) women treated with diet only had pregnancy complications. Primiparity and higher weight gain during pregnancy were the best predictors for complications (predictive probability 0.586 and 0.603). CONCLUSION: In this GDM population we found various relevant factors predicting the need for insulin therapy. A fasting glucose level ≥ 5.5 mmol/l at GDM diagnosis was by far the strongest predictor. Women with GDM who had good glycaemic control on diet only with a higher parity and less weight gain had a lower risk for pregnancy complications.

Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women.

OBJECTIVE: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. DESIGN: Post hoc analysis of frozen fFN samples of a nationwide cohort study. SETTING: Ten perinatal centres in the Netherlands. POPULATION: Symptomatic women between 24 and 34 weeks of gestation. METHODS: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. MAIN OUTCOME MEASURES: Spontaneous delivery within 7 days after study entry. RESULTS: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. CONCLUSION: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. TWEETABLE ABSTRACT: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD.

Muscle ultrasound density in human fetuses with spina bifida aperta.

BACKGROUND: In fetal spina bifida aperta (SBA), leg movements caudal to the meningomyelocele (MMC) are transiently present, but they disappear shortly after birth. Insight in the underlying mechanism could help to improve treatment strategies. In fetal SBA, the pathogenesis of neuromuscular damage prior to movement loss is still unknown. We reasoned that prenatal assessment of muscle ultrasound density (fetal-MUD) could help to reveal whether progressive neuromuscular damage is present in fetal SBA, or not. AIM: To reveal whether prenatal neuromuscular damage is progressively present in SBA. PATIENTS/METHODS: In SBA fetuses (n=6; 22-37 weeks gestational age), we assessed fetal-MUD in myotomes caudal to the MMC and compared measurements between myotomes cranial to the MMC and controls (n=11; 17-36 weeks gestational age). Furthermore, we intra-individually compared MUD and muscle histology between the pre- and postnatal period. RESULTS: Despite persistently present fetal leg movements caudal to the MMC, fetal-MUD was higher caudal to the MMC than in controls (p<0.05). Fetal-MUD caudal to the MMC did not increase with gestational age, whereas fetal-MUD in controls and cranial to the MMC increased with gestational age (p<0.05). In 5 of 6 patients assessed, comparison between pre- and postnatal MUD and/or muscle histology indicated consistent findings. CONCLUSIONS: In fetal SBA, persistent leg movements concur with stable, non-progressively increased fetal-MUD. These data may implicate that early postnatal loss of leg movements is associated with the impact of additional neuromuscular damage after the prenatal period.

[Management of pregnancy and childbirth in carriers of haemophilia]. / Begeleiding van de zwangerschap en de partus bij draagsters van hemofilie.

3 pregnant women, aged 27, 33 and 31 years respectively, were carriers of haemophilia A. The first patient had a caesarean section without prior measurement or substitution of factor VIII. She gave birth to a healthy boy, but developed severe diffuse abdominal bleeding after a few hours. The second patient had a normal level of factor VIII, and lived 100 km away from the nearest haemophilia treatment centre. Ultrasound investigation revealed a female foetus. She gave birth in the local hospital. The third patient was pregnant with a male foetus, but refused further prenatal investigation. Contrary to medical advice she gave birth at home. For carriers of haemophilia, there are several options for prenatal diagnosis and managing labour and delivery. Early referral is advised and the need for adequate counselling is explained. It is important to have an experienced haemophilia treatment centre nearby, where haematologists, gynaecologists, geneticists and paediatricians cooperate in caring for pregnant carriers of haemophilia.

Spinal hemorrhages are associated with early neonatal motor function loss in human spina bifida aperta.

BACKGROUND: In spina bifida aperta (SBA), leg movements caudal to the meningomyelocele are present in utero, but they disappear shortly after birth. It is unclear whether leg movements disappear by impact of the neuro-developmental malformation or by superimposed traumatic damage. If superimposed traumatic damage is involved, targeted fetal intervention could improve motor outcome. AIM: To characterize neuromuscular pathology in association with perinatal motor function loss in SBA. PATIENTS/METHODS: In fetal SBA (n=8; 16-40 weeks GA), the median time interval between ultrasound registrations of fetal motor behavior and post-mortem histology was 1 week. Histology was assessed cranial, at and caudal to the meningomyelocele and compared with findings in fetal controls (n=4). RESULTS: Despite fetal movements caudal to the meningomyelocele (5/6), histology indicated muscle fiber alterations (6/6) that concurred with neuro-developmental and traumatic spinal defects [Neuro-developmental defects: spinal ependymal denudation (3/8), reduced amount of (caspase3-negative) lower motor neurons (LMNs; 8/8), aberrant spinal vascularization (8/8). Traumatic defects: gliosis (7/8), acute/fresh spinal hemorrhages near LMNs (8/8)]. CONCLUSION: In all delivered SBA patients, recent spinal hemorrhages were superimposed upon pre-existing defects. If early therapeutic strategies can prevent these superimposed secondary spinal hemorrhages, motor outcome may improve.

Non-cardiac complications during pregnancy in women with isolated congenital pulmonary valvar stenosis.

BACKGROUND: Information on the outcome of pregnancy in patients with pulmonary valvar stenosis is scarce, mostly limited to cardiac complications observed during pregnancy. OBJECTIVES: To investigate the magnitude and determinants of non-cardiac and fetal risks during pregnancy of women with isolated pulmonary valvar stenosis. METHODS: Using the nationwide registry (CONgenital CORvitia), 106 women with (un-)corrected pulmonary valvar stenosis receiving care in six tertiary medical centres in The Netherlands were included. A total of 51 women had 108 pregnancies, including 21 (19%) miscarriages and 6 elective abortions. RESULTS: In the 81 completed (>20 weeks of gestation) pregnancies, we observed a high number of hypertension-related disorders (n = 12, 15%, including pre-eclampsia (n = 4) and eclampsia (n = 2)), premature deliveries (n = 14, 17%, including one twin) and thromboembolic events (n = 3, 3.7%). Furthermore, recurrence of congenital heart defects in the offspring was detected in three children (3.7%, pulmonary valvar stenosis (n = 2) and complete transposition of the great arteries in combination with anencephaly). In addition to the intrauterine fetal demise of the transposition child, three other children died shortly after birth owing to immaturity, hydrocephalus combined with prematurity and meningitis (overall offspring mortality, 4.8%). CONCLUSION: In this largest report on pregnancy in women with (un-) corrected isolated pulmonary valvar stenosis, an excessive number of (serious) non-cardiac complications and mortality were observed in the offspring.

Pregnancy and delivery in women after Fontan palliation.

OBJECTIVES: To evaluate the outcome of pregnancy in women after Fontan palliation and to assess the occurrence of infertility and menstrual cycle disorders. DESIGN AND PATIENTS: Two congenital heart disease registries were used to investigate 38 female patients who had undergone Fontan palliation (aged 18-45 years): atriopulmonary anastomosis (n = 23), atrioventricular connection (n = 5) and total cavopulmonary connection (n = 10). RESULTS: Six women had 10 pregnancies, including five miscarriages (50%) and one aborted ectopic pregnancy. During the remaining four live-birth pregnancies clinically significant complications were encountered: New York Heart Association class deterioration; atrial fibrillation; gestational hypertension; premature rupture of membranes; premature delivery; fetal growth retardation and neonatal death. Four of seven women who had attempted to become pregnant reported female infertility: non-specified secondary infertility (n = 2), uterus bicornis (n = 1) and related to endometriosis (n = 1). Moreover, several important menstrual cycle disorders were documented. In particular, the incidence of primary amenorrhoea was high (n = 15, 40%), which resulted in a significant increase in age at menarche (14.6 (SD 2.1) years, p < 0.0001, compared with the general population). CONCLUSION: Women can successfully complete pregnancy after adequate Fontan palliation without important long-term sequelae, although it is often complicated by clinically significant (non-)cardiac events. In addition, subfertility or infertility and menstrual disorders were common.

Movement analysis in neonates with spina bifida aperta.

INTRODUCTION: In neonates with spina bifida aperta (SBA), leg movements by myotomes caudal to the meningomyelocele (MMC) are transiently observed. It is unclear whether these leg movements relate to functional neural conduction through the MMC. For optimal therapeutical intervention, pathophysiological insight in these transient leg movements seems relevant. If leg movements by myotomes caudal to the MMC concur with the execution of general movements (GMs), functional neural conduction through the MMC is implicated. OBJECTIVE: In neonates with SBA, we aimed to determine whether the transiently present leg movements caudal to the MMC indicate functional neural conduction through the MMC. METHODS: During the perinatal period, fetuses and neonates with SBA (n = 7 and n = 13, respectively) were longitudinally analysed for concurrency between leg movements caudal to the MMC and GMs. To address the integrity of the reflex arc in spinal segments (at, or) caudal to the MMC, tendon leg reflexes were assessed during the first postnatal week. RESULTS: At postnatal day 1, leg movements caudal to the MMC concurred with GMs in 12 of 13 infants. Isolated leg movements were observed in only 3 of these 12 infants (isolated vs. concurrent; p < 0.005). Leg movements concurring with GMs lasted longer than isolated leg movements (median duration = 11 s vs. 2 s; p < 0.05). Between days 1 and 7, tendon leg reflexes (at, or) caudal to the MMC had disappeared in all but 1 neonate. However, leg movements caudal to the MMC remained concurrently present with GMs in all five neonates available for follow-up after day 7. Comparing these leg movements between days 1 and 7 indicated a decreased duration (-44%, p < 0.05). CONCLUSIONS: In neonates with SBA, leg movements caudal to the MMC concur with GMs, indicative of functional neural conduction through the MMC. The disappearance of these leg movements is caused by lower motor neuron dysfunction at the reflex arc, whereas neural conduction through the MMC is still functional.