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Background: At present, women with threatened preterm labor before 32 weeks of gestation are, after transfer to a perinatal center, treated with tocolytics and corticosteroids. Many of these women are treated unnecessarily. Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labor. We will assess whether triage of these women with fibronectin testing, cervical length or their combination is cost-effective.Methods/design: We will investigate a prospective cohort of women referred to a perinatal centre for spontaneous threatened preterm labor between 24 and 34 weeks with intact membranes. All women will be tested for fibronectin and cervical length. Women with a cervical length <10 mm and women with a cervical length between 10-30 mm in combination with a positive fibronectin test will be treated with tocolytics according to local protocol. Women with a cervical length between 10-30 mm in combination with a negative fibronectin test will be randomised between treatment with nifedipine (intervention) and placebo (control) for 48 hours. Women with a cervical length > 30 mm will be managed according to local protocol. Corticosteroids may be given to all women at the discretion of the attending physician. Primary outcome measure will be delivery within 7 days. Secondary outcome measures will be neonatal morbidity and mortality, complications of tocolytics, costs and health related quality of life. The analysis will be according to the intention to treat principle. We anticipate the probability on preterm birth within 7 days in the group of women with a negative fibronectine test to be 5%. Two groups of 110 women will be needed to assure that in case of non-inferiority the difference in the proportion of preterm deliveries < 7 days will be within a prespecified boundary of 7.5% (one sided test, beta 0.2, alpha 0.05). Data obtained from women with a positive and negative fibronectin tests in both the cohort study and the trial will be integrated in a cost-effectiveness analysis that will assess economic consequences of the use of fibronectin.Discussion: This study will provide evidence for the use of fibronectin testing as safe and cost-effective method in a triage for threatened preterm labor.Trial Registration: Nederlands Trial Register (NTR) number 1857, http://www.trialregister.nl. [ABSTRACT FROM AUTHOR]

Muscle ultrasound density (MUD) is a non-invasive parameter to indicate neuromuscular integrity in both children and adults. In healthy fetuses and infants, physiologic MUD values during development are still lacking. We therefore aimed to determine the physiologic, age-related MUD trend of biceps, quadriceps, tibialis anterior, hamstrings, gluteal and calf muscles, from pre- to the first year of postnatal life. To avoid a bias by pregnancy-related signal disturbances, we expressed fetal MUD as a ratio against bone ultrasound density. We used the full-term prenatal MUD ratio and the newborn postnatal MUD value as reference points, so that MUD development could be quantified from early pre- into postnatal life. Results: During the prenatal period, the total muscle group revealed a developmental MUD trend concerning a fetal increase in MUD-ratio from the 2nd trimester up to the end of the 3rd trimester [median increase: 27% (range 16-45), p < .001]. After birth, MUD-values increased up to the sixth month [median increase: 11% (range -7-27), p = 0.025] and stabilized thereafter. Additionally, there were also individual MUD characteristics per muscle group and developmental stage, such as relatively low MUD values of fetal hamstrings and high values of the paediatric gluteus muscles. These MUD trends are likely to concur with analogous developmentally, maturation-related alterations in the muscle water to peptide content ratios., Competing Interests: The authors have declared that no competing interests exist.

Background: We evaluate pregnancy outcome and anticoagulation regimes in women with mechanical and biological prosthetic heart valves (PHV) for congenital heart disease., Methods: Retrospective multicenter cohort studying pregnancy outcomes in an existing cohort of patients with PHV., Results: 52 women had 102 pregnancies of which 78 pregnancies (46 women) ≥20 weeks duration (59 biological, 19 mechanical PHV). Miscarriages (n = 19, ≤20 weeks) occurred more frequently in women using anticoagulation (P < .05). During 42% of pregnancies of women with mechanical PHV a combined low molecular weight heparin (LMWH) vitamin-K-antagonist anticoagulation regime was used (n = 8). Overall, cardiovascular, obstetric and fetal/neonatal complications occurred in 17% (n = 13), 68% (n = 42) and 42% (n = 27) of the pregnancies. Women with mechanical PHV had significantly higher cardiovascular (12% vs 32%, P < .05), obstetric (59% vs 85%, P = .02) and fetal/neonatal (34% vs 61%, P < .05) complication rates than women with biological PHV. This was related to PHV thrombosis (n = 3, P < .02), post-partum hemorrhage (P < .02), cesarean section (P < .02), low birth weight and small for gestational age (both P < .05). PHV thrombosis occurred in 3 pregnancies, including 2/5 pregnancies with pulmonary mechanical PHV. PHV thrombosis was related to necessary cessation of anticoagulation therapy or insufficient monitoring of LMWH. Other cardiovascular complications occurred equally frequent in both groups., Conclusion: Complications occur more often in pregnancies of women with a mechanical PHV than in women with a biological PHV, mainly caused by PHV thrombosis and bleeding complications. Meticulous monitoring of anticoagulation in pregnant women is necessary. Women with a pulmonary mechanical PHV are at high risk of complications., (Copyright © 2018. Published by Elsevier B.V.)

Objective: To determine whether women delivering preterm have unfavorable cardiovascular profiles as compared with women who deliver at term., Methods: A prospective observational cohort study enrolled 165 women with spontaneous preterm delivery (sPTD) at 24 +0 and 36 +6 gestational weeks in three perinatal care centers in The Netherlands between August 2012 and August 2014. Total cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein, glucose, and homocysteine were measured within 24 hours after delivery. Lipids and cardiovascular biochemical risk factors were compared between women with sPTD and an external comparison group of 30 women with term delivery via analysis of covariance., Results: Mean gestational age at delivery was 30.7 ± 3.6 weeks in the sPTD group and 40.3 ± 1.3 weeks in the reference group. Data were adjusted for body mass index, age, and center. As compared with the reference group, total cholesterol and LDL-cholesterol levels were lower and glucose levels were higher among women with sPTD., Conclusion: An association between sPTD and unfavorable lipids and cardiovascular biochemical risk factors was not established. The higher levels of glucose in the sPTD group might be due to increased insulin resistance, which is associated with a higher risk of sPTD., (© 2017 International Federation of Gynecology and Obstetrics.)

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., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective  We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days. Methods  We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome. Results  Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12-0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7-12). Conclusion  The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

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., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Objective: The objective of this study is to evaluate the relation among fetal gender, ethnicity, and preterm labor (PTL) and preterm delivery (PTD)., Methods: A secondary analysis was performed of a prospective cohort study including women with symptoms of PTL between 24 and 34 weeks. The proportion of women carrying a male or female fetus at the onset of PTL was calculated. Gestational age at delivery and risk of PTD of both fetal genders was compared and interaction of fetal gender and maternal ethnicity on the risk of PTD was evaluated., Results: Of the 594 included women, 327 (55%) carried a male fetus. Median gestational age at delivery in women pregnant with a male fetus was 37 5/7 (IQR 34 4/7-39 1/7) weeks compared with 38 1/7 (IQR 36 0/7-39 5/7) weeks in women pregnant with a female fetus (p = 0.032). The risk of PTD did not differ significantly. In Caucasians, we did find an increased risk of PTD before 37 weeks in women pregnant with a male fetus (OR 1.9 (95% CI 1.2-3.0))., Conclusions: The majority of women with PTL are pregnant with a male fetus and these women deliver slightly earlier. Race seems to affect this disparity.

Objective: To compare the accuracy of the Actim Partus test and fetal fibronectin (fFN) test in the prediction of spontaneous preterm delivery within seven days in symptomatic women undergoing cervical length measurement., Study Design: We performed a post-hoc analysis on frozen samples of a nationwide cohort study in all 10 perinatal centres in the Netherlands. We selected samples from women with signs of preterm labour between 24 and 34 weeks of gestational age and a cervical length below 30mm. Delivery within seven days after initial assessment was the primary endpoint. We calculated sensitivity, specificity, and positive and negative predictive values for the combination of both the Actim Partus test and fFN test with cervical length. A test was considered positive in case of a cervical length between 15 and 30mm with a positive Actim Partus or fFN test, and a cervical length below 15mm regardless the test result., Results: In total, samples of 350 women were tested, of whom 69 (20%) delivered within seven days. Eighty-four women had a positive Actim Partus test and 162 women a positive fFN test, of whom 54 (64%) and 63 (39%) delivered within seven days, respectively. Ninety-seven women had a cervical length below 15mm, of whom 50 (52%) delivered within seven days. Sensitivity, specificity, positive and negative predictive values of combining cervical length with the Actim Partus test or the fFN test were 91%, 75%, 47% and 97%, and 96%, 58%, 36% and 98%, respectively., Conclusion: According to this post-hoc study, in combination with cervical length, the Actim Partus test could be used as an alternative for the fFN test to identify women who will not deliver within seven days after presentation. Further evidence should be collected in a prospective comparative study., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment - diet-only versus additional insulin therapy - were based on the 2010 national Dutch guidelines., Methods: Retrospective study of the electronic medical files of 820 singleton GDM pregnancies treated between January 2011 and September 2014 in a university and non-university hospital. Pregnancy outcomes were compared between regular care treatment regimens -diet-only versus additional insulin therapy- and pregnancy outcomes of the Northern region of the Netherlands served as a reference population., Results: A total of 460 women (56 %) met glycaemic control on diet-only and 360 women (44 %) required additional insulin therapy. Between the groups, there were no differences in perinatal complications (mortality, birth trauma, hyperbilirubinaemia, hypoglycaemia), small for gestational age, large for gestational age (LGA), neonate weighing >4200 g, neonate weighing ≥4500 g, Apgar score <7 at 5 min, respiratory support, preterm delivery, and admission to the neonatology department. Neonates born in the insulin-group had a lower birth weight compared with the diet-group (3364 vs. 3467 g, p = 0.005) and a lower gestational age at birth (p = 0.001). However, birth weight was not different between the groups when expressed in percentiles, adjusted for gestational age, gender, parity, and ethnicity. The occurrence of preeclampsia and gestational hypertension was comparable between the groups. In the insulin-group, labour was more often induced and more planned caesarean sections were performed (p = 0.001). Compared with the general obstetric population, the percentage of LGA neonates was higher in the GDM population (11.0 % vs.19.9 %, p = <0.001)., Conclusions: Neonatal and obstetric outcomes were comparable either with diet-only or additional insulin therapy. However, compared with the general obstetric population, the incidence of LGA neonates was significantly increased in this GDM cohort.

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.

Objective The aim of this study was to assess which characteristics and results of vaginal examination are predictive for delivery within 7 days, in women with threatened preterm labor after initial treatment. Study Design A secondary analysis of a randomized controlled trial on maintenance nifedipine includes women who remained undelivered after threatened preterm labor for 48 hours. We developed one model for women with premature prelabor rupture of membranes (PPROM) and one without PPROM. The predictors were identified by backward selection. We assessed calibration and discrimination and used bootstrapping techniques to correct for potential overfitting. Results For women with PPROM (model 1), nulliparity, history of preterm birth, and vaginal bleeding were included in the multivariable analysis. For women without PPROM (model 2), maternal age, vaginal bleeding, cervical length, and fetal fibronectin (fFN) status were in the multivariable analysis. Discriminative capability was moderate to good (c-statistic 0.68; 95% confidence interval [CI] 0.60-0.77 for model 1 and 0.89; 95% CI, 0.84-0.93 for model 2). Conclusion PPROM and vaginal bleeding in the current pregnancy are relevant predictive factors in all women, as are maternal age, cervical length, and fFN in women without PPROM and nulliparity, history of preterm birth in women with PPROM.

Despite adequate glycemic control, pregnancy outcome of women with type 1 diabetes (T1D) is still unfavorable as compared to healthy women. In a rat-model of T1D under normoglycemic conditions, adverse pregnancy outcome was also observed, which was associated with aberrant immunological adaptations to pregnancy. Because similar processes may occur in women with T1D we studied the systemic immune response in non-pregnant and pregnant women with and without T1D. The systemic immune response was assessed by using flow cytometry to evaluate the number and activational status of subpopulations of lymphocytes, Natural Killer cells and monocytes in peripheral blood of non-pregnant and pregnant women with and without T1D. An increased white blood cell count, an increased Th1/Th2 ratio, increased Natural Killer cell expression of CD335 and enhanced activation of intermediate and non-classical monocytes was observed in pregnant women with T1D vs. healthy pregnant women. Also, the pregnancy outcome (i.e. incidence of preterm delivery and macrosomia) of women with T1D was unfavorable as compared to healthy women. This study showed that in T1D, the immunological adaptations to pregnancy are disturbed. In addition to hyperglycemia, these different immunological adaptations may be responsible for the greater frequency of complications in pregnant women with T1D.

Objective: To assess whether patient characteristics add to the fetal fibronectin test and cervical length measurement in the prediction of preterm delivery in symptomatic women., Study Design: A nationwide prospective cohort study was conducted in all ten perinatal centres in the Netherlands. Women with symptoms of preterm labour between 24 and 34 weeks gestation with intact membranes were invited. In all women qualitative fibronectin testing (0.050 μg/mL cut-off) and cervical length measurement were performed. Only singleton pregnancies were included in this analysis. Logistic regression was used to construct two multivariable models to predict spontaneously delivery within 7 days: a model including cervical length and fetal fibronectin as predictors, and an extended model including all potential predictors. The models were internally validated using bootstrapping techniques. Predictive performances were assessed as the area under the receiver operator characteristic curve (AUC) and calibration plots. We compared the models' capability to identify women with a low risk to deliver within 7 days. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25 mm, was considered as low risk., Results: Seventy-three of 600 included women (12%) had delivered spontaneously within 7 days. The extended model included maternal age, parity, previous preterm delivery, vaginal bleeding, C-reactive protein, cervical length, dilatation and fibronectin status. Both models had high discriminative performances (AUC of 0.92 (95% CI 0.88-0.95) and 0.95 (95% CI 0.92-0.97) respectively). Compared to the model with fibronectin and cervical length, our extended model reclassified 38 women (6%) from low risk to high risk and 21 women (4%) from high risk to low risk. Preterm delivery within 7 days occurred once in both the reclassification groups., Conclusion: In women with symptoms of preterm labour before 34 weeks gestation, a model that integrates maternal characteristics, clinical signs and laboratory tests, did not predict delivery within 7 days better than a model with only fibronectin and cervical length., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess the impact of cervical length (CL) measurement and fetal fibronectin testing (fFN) on the clinicians' decision to prescribe antenatal corticosteroids (ACS) to women with symptoms of preterm labor., Study Design: This is a secondary analysis of a prospective cohort study including women with symptoms of preterm labor and intact membranes between 24 and 34 weeks' gestation. We compared the proportion prescribed and completed ACS courses, preterm delivery within seven days and median intervals from ACS to delivery in four groups: group 1 CL<10 mm, group 2 CL 10-30 mm and positive fFN, group 3 CL 10-30 mm and negative fFN, group 4 CL>30 mm., Results: ACS were prescribed to 63/65 (97%) women in group 1, 176/192 (91%) in group 2, 111/172 women (65%) in group 3 and 55/242 (23%) in group 4. In group 1, 42 (65%) women delivered within seven days, compared to 34 (18%) in group 2, 6 (3%) in group 3 and 3 (1%) in group 4. Median intervals between ACS and delivery were 6 days (IQR 3-61 days), 44 days (IQR 17-69 days), 53 days (IQR 37-77 days) and 66 days (IQR 43-78 days) in group 1, 2, 3 and 4 respectively., Conclusion: ACS were prescribed frequently to women with a CL of 10-30 mm and a negative fFN test or a CL>30 mm. There is room for improvement in the prescription of ACS in these low risk women., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate whether tocolysis with nifedipine can be omitted in women with symptoms of preterm labor, a shortened cervix, and negative fetal fibronectin test., Study Design: A randomized noninferiority trial was performed in all Dutch perinatal centers. Women with symptoms of preterm labor between 24 and 34 weeks, intact membranes, cervical length between 10 and 30 mm, and negative fibronectin test were randomly allocated to nifedipine (80 mg/day) or placebo. The primary outcome was delivery within 7 days. Secondary outcomes were severe neonatal morbidity and mortality. We also followed all eligible nonrandomized women., Results: We allocated 37 women to nifedipine and 36 women to placebo. In the nifedipine group, three women (8.1%) delivered within 7 days, compared with one woman (2.8%) in the placebo group (difference -5.3%; one-sided 95% confidence limit 4.5%). Median gestational age at delivery were respectively 37 + 0 (interquartile range [IQR] 34 + 6 to 38 + 5) and 38 + 2 (IQR 37 + 0 to 39 + 6) weeks (p = 0.008). In the nifedipine group, three pregnancies (8.1%) had a poor outcome; there were no poor outcomes in the placebo group. We observed similar trends in eligible nonrandomized women., Conclusion: In symptomatic women with preterm labor, a shortened cervix, and negative fibronectin test, placebo treatment is not inferior to tocolysis with nifedipine., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To estimate the performance of combining cervical length measurement with fetal fibronectin testing in predicting delivery in women with symptoms of preterm labor., Methods: We conducted a prospective nationwide cohort study in all 10 perinatal centers in The Netherlands. Women with symptoms of preterm labor between 24 and 34 weeks of gestation with intact membranes were included. In all women, qualitative fibronectin testing (0.050-microgram/mL cutoff) and cervical length measurement were performed. Logistic regression was used to predict spontaneous preterm delivery within 7 days after testing. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25 mm, was considered as low risk., Results: Between December 2009 and August 2012, 714 women were enrolled. Fibronectin results and cervical length were available for 665 women, of whom 80 (12%) delivered within 7 days. Women with a cervical length of at least 30 mm or with a cervical length between 15 and 30 mm with a negative fibronectin result were at low risk (less than 5%) of spontaneous delivery within 7 days. Fibronectin testing in case of a cervical length between 15 and 30 mm additionally classified 103 women (15% of the cohort) as low risk and 36 women (5% of the cohort) as high risk., Conclusion: Cervical length measurement, combined with fetal fibronectin testing in case of a cervical length between 15 and 30 mm, improves identification of women with a low risk to deliver spontaneously within 7 days., Level of Evidence: II.

Background: Pregnant women with congenital heart disease (CHD) are susceptible to cardiovascular, obstetric, and offspring complications. In women with CHD, cardiac dysfunction may compromise uteroplacental flow and contribute to the increased incidence of obstetric and offspring events., Methods and Results: We performed a prospective multicenter cohort study of pregnant women with CHD and healthy pregnant women. We compared clinical, laboratory, echocardiographic, and uteroplacental Doppler flow (UDF) parameters at 20 and 32 weeks gestation, and pregnancy outcome. We related cardiovascular parameters to UDF parameters and pregnancy outcome in women with CHD. We included 209 women with CHD and 70 healthy women. Cardiovascular parameters (N-terminal pro-B-type natriuretic peptide, left and right ventricular function) differed between both groups. UDF parameters were impaired in CHD women (umbilical artery pulsatility and resistance index at 32 weeks in CHD versus healthy women, P=0.0085 and P=0.017). The following cardiovascular parameters prepregnancy and at 20 weeks gestation were associated with UDF (umbilical artery resistance index) at 32 weeks at multivariable analysis: (1) right ventricular function (tricuspid annular plane systolic excursion) (P=0.002), (2) high N-terminal pro-B-type natriuretic peptide (P=0.085), (3) systemic (P=0.001), and (4) pulmonary (P=0.045) atrioventricular valve regurgitation. Women with CHD had more obstetric (58.9% versus 32.9%, P<0.0001) and offspring events (35.4% versus 18.6%, P=0.008) than healthy women. Impaired UDF was associated with adverse obstetric and offspring outcome., Conclusions: UDF parameters are abnormal in pregnant women with CHD. Cardiovascular function is associated with an abnormal pattern of UDF. Compromised UDF may be a key factor in the high incidence of offspring and obstetric complications in this population.

Objective: To estimate the association between pre-existing maternal and pregnancy-related factors and developmental delay in early childhood in moderately preterm-born children., Methods: We measured development with the Ages and Stages Questionnaire at age 43-49 months in 834 moderately preterm-born (between 32 0/7 and 35 6/7 weeks of gestation) children born in 2002-2003. We obtained data on preexisting maternal, maternal pregnancy-related, fetal, and delivery-related factors. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) and attributable risks for developmental delay adjusted for sociodemographic and lifestyle variables., Results: Attributable risk for developmental delay for small-for-gestational-age (SGA, as a proxy for intrauterine growth restriction [IUGR]) was 14.2% (SGA 21.9%, no SGA 7.7%, P<.05, adjusted OR 2.75, CI 1.25-6.08), for preexisting maternal obesity 10.5% (obesity 18.0%, no obesity 7.5%, P<.01, adjusted OR 2.73, CI 1.35-5.52), for multiple pregnancy 4.2% (multiple 12.0%, singleton 7.8%, P<.05, adjusted OR 1.86, CI 1.02-3.42), and for male sex 9.3% (male 13.0%, female 3.8%, P<.001, adjusted OR 4.20, CI 2.09-8.46). No other preexisting or pregnancy-related maternal factors or any delivery-related factors were associated with increased risk of developmental delay., Conclusions: Of all preexisting maternal and pregnancy-related factors studied, SGA, maternal prepregnancy obesity, being one of a multiple, and male sex were associated with the risk of developmental delay in early childhood after moderately preterm birth. Reinforced focus on prevention of IUGR, preconception lifestyle interventions aiming at weight reduction in fertile women, and reinforced efforts to reduce rates of multiple pregnancies in assisted reproduction may all contribute toward more favorable developmental outcomes in moderately preterm-born children., Level of Evidence: II.

Importance: In threatened preterm labor, maintenance tocolysis with nifedipine, after an initial course of tocolysis and corticosteroids for 48 hours, may improve perinatal outcome., Objective: To determine whether maintenance tocolysis with nifedipine will reduce adverse perinatal outcomes due to premature birth., Design, Setting, and Participants: APOSTEL-II (Assessment of Perinatal Outcome with Sustained Tocolysis in Early Labor) is a double-blind, placebo-controlled trial performed in 11 perinatal units including all tertiary centers in The Netherlands. From June 2008 to February 2010, women with threatened preterm labor between 26 weeks (plus 0 days) and 32 weeks (plus 2 days) gestation, who had not delivered after 48 hours of tocolysis and a completed course of corticosteroids, were enrolled. Surviving infants were followed up until 6 months after birth (ended August 2010)., Intervention: Randomization assigned 406 women to maintenance tocolysis with nifedipine orally (80 mg/d; n = 201) or placebo (n = 205) for 12 days. Assigned treatment was masked from investigators, participants, clinicians, and research nurses., Main Outcome Measures: Primary outcome was a composite of adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage >grade 2, periventricular leukomalacia >grade 1, or necrotizing enterocolitis). Analyses were completed on an intention-to-treat basis., Results: Mean (SD) gestational age at randomization was 29.2 (1.7) weeks for both groups. Adverse perinatal outcome was not significantly different between groups: 11.9% (24/201; 95% CI, 7.5%-16.4%) for nifedipine vs 13.7% (28/205; 95% CI, 9.0%-18.4%) for placebo (relative risk, 0.87; 95% CI, 0.53-1.45)., Conclusions and Relevance: In patients with threatened preterm labor, nifedipine-maintained tocolysis did not result in a statistically significant reduction in adverse perinatal outcomes when compared with placebo. Although the lower than anticipated rate of adverse perinatal outcomes in the control group indicates that a benefit of nifedipine cannot completely be excluded, its use for maintenance tocolysis does not appear beneficial at this time., Trial Registration: trialregister.nl Identifier: NTR1336.

Background: In women with corrected tetralogy of Fallot (ToF), pregnancy is associated with maternal cardiac, obstetric, and offspring complications. Our aim is to investigate the magnitude and determinants of pregnancy outcome in women with corrected ToF., Methods: In this retrospective international multicenter study using 2 congenital heart disease registries, 204 women with corrected ToF were identified. Within this group, 74 women had 157 pregnancies, including 30 miscarriages and 4 terminations of pregnancy. Detailed information on each completed pregnancy (n = 123) was obtained using medical records and supplementary interviews., Results: Cardiovascular events occurred during 10 (8.1%) pregnancies, mainly (supra)ventricular arrhythmias. Obstetric and offspring events occurred in 73 (58.9%) and 42 (33.9%) pregnancies, respectively, including offspring mortality in 8 (6.4%). The most important predictor was use of cardiac medication before pregnancy (odds ratio for cardiac events 11.7, 95% CI 2.2-62.7; odds ratio for offspring events 8.4, 95% CI 1.4-48.6). In pregnancies with cardiovascular events, significantly more small-for-gestational-age children were born (P value < .01)., Conclusions: Cardiovascular, obstetric, and offspring events occur frequently during pregnancies in women with ToF. Maternal use of cardiovascular medication is associated with pregnancy outcome, and maternal cardiovascular events during pregnancy are highly associated with offspring events., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Previous research has shown that women with congenital heart disease (CHD) are more susceptible to cardiovascular, obstetric, and offspring events. The causative pathophysiologic mechanisms are incompletely understood. Inadequate uteroplacental circulation is an important denominator in adverse obstetric events and offspring outcome. The relation between cardiac function and uteroplacental perfusion has not been investigated in women with CHD. Moreover, the effects of physiologic changes on pregnancy-related events are unknown. In addition, long-term effects of pregnancy on cardiac function and exercise capacity are scarce., Methods: Zwangerschap bij Aangeboren Hartafwijking (ZAHARA) II, a prospective multicenter cohort study, investigates changes in and relations between cardiovascular parameters and uteroplacental Doppler flow patterns during pregnancy in women with CHD compared to matched healthy controls. The relation between cardiovascular parameters and uteroplacental Doppler flow patterns and the occurrence of cardiac, obstetric, and offspring events will be investigated. At 20 and 32 weeks of gestation, clinical, neurohumoral, and echocardiographic evaluation and fetal growth together with Doppler flow measurements in fetal and maternal circulation are performed. Maternal evaluation is repeated 1 year postpartum., Implications: By identifying the factors responsible for pregnancy-related events in women with CHD, risk stratification can be refined, which may lead to better pre-pregnancy counseling and eventually improve treatment of these women., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Monochorionic (MC) twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS) or intrauterine co-twin death) or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC) twins at the age of two years., Methods: This was a prospective cohort study. Cerebral palsy (CP) was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (un)alikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner., Findings: Four out of 182 MC infants had CP (2.2%) - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death) and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5-38.2) of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7%) had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0-1.4). Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its larger co-twin., Conclusions: There were no significant differences in occurrence of cerebral palsy as well as neurodevelopmental outcome between MC and DC twins. Outcome of MC twins seems favourable in the absence of TTTS or co-twin death.

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.

Objective: To study perinatal mortality and neonatal morbidity in a large cohort of monoamniotic twin pregnancies with special emphasis to the gestational age-specific mortality., Methods: The study included monoamniotic twin pregnancies delivered in 10 perinatal centers in the Netherlands between January 2000 and December 2007., Results: A total of 98 monoamniotic pregnancies were included. The perinatal mortality rate (20 weeks of gestation through 28 days of life) was 19%; after exclusion of fetuses with lethal anomalies, the rate was 17%. After 32 weeks of gestation, only two pregnancies were complicated by perinatal mortality (4%). The incidence of twin-twin transfusion syndrome was 6%. The incidence of congenital heart anomalies and cerebral injury was 4% and 5%, respectively., Conclusion: The current incidence of perinatal mortality in monoamniotic twins is considerably lower than in previous decades, but it is still high and occurs throughout pregnancy., Level of Evidence: III.

Objectives: To investigate the age at menarche, the prevalence of menstrual cycle (interval) disorders, and determinants in women with congenital heart disease (CHD)., Design: Using two CHD registries, 1802 (82%) of the 2196 women with CHD contacted (aged 18-58 years) provided written informed consent. After exclusion of patients with genetic disorders known to be associated with menstrual cycle disorders, 1593 eligible patients remained. Interviews by telephone and reviews of medical records were conducted., Results: Overall, the age at menarche was slightly increased in women with CHD (13.3 vs. 13.1 years in the general population), mainly attributable to an increased prevalence of primary amenorrhea (n = 147; 9.2%). Other menstrual cycle disorders were documented: secondary amenorrhea (n = 181, 11.4%), polymenorrhea (n = 103, 6.5%), oligomenorrhea (n = 90, 5.6%), and menorrhagia (n = 117, 6.5%). The occurrence of these disorders also depended on the presence of cyanotic heart disease, surgical status, the number of surgical interventions, and the severity of CHD., Discussion: Menstrual cycle disturbances, in particular primary amenorrhea, were frequently observed in this population. Patients with complex (cyanotic) heart disease needing repeated surgical interventions prior to menarche are especially at risk.

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.

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.

Background: Fetal spina bifida aperta (SBA) is characterized by a spinal meningomyelocele (MMC) and associated with cerebral pathology, such as hydrocephalus and Chiari II malformation. In various animal models, it has been suggested that a loss of ventricular lining (neuroepithelial/ependymal denudation) may trigger cerebral pathology. In fetuses with MMC, little is known about neuroepithelial/ependymal denudation and the initiating pathological events.The objective of this study was to investigate whether neuroepithelial/ependymal denudation occurs in human fetuses and neonates with MMC, and if so, whether it is associated with the onset of hydrocephalus., Methods: Seven fetuses and 1 neonate (16-40 week gestational age, GA) with MMC and 6 fetuses with normal cerebral development (22-41 week GA) were included in the study. Identification of fetal MMC and clinical surveillance of fetal head circumference and ventricular width was performed by ultrasound (US). After birth, MMC was confirmed by histology. We characterized hydrocephalus by increased head circumference in association with ventriculomegaly. The median time interval between fetal cerebral ultrasound and fixing tissue for histology was four days., Results: At 16 weeks GA, we observed neuroepithelial/ependymal denudation in the aqueduct and telencephalon together with sub-cortical heterotopias in absence of hydrocephalus and/or Chiari II malformation. At 21-34 weeks GA, we observed concurrence of aqueductal neuroepithelial/ependymal denudation and progenitor cell loss with the Chiari II malformation, whereas hydrocephalus was absent. At 37-40 weeks GA, neuroepithelial/ependymal denudation coincided with Chiari II malformation and hydrocephalus. Sub-arachnoidal fibrosis at the convexity was absent in all fetuses but present in the neonate., Conclusion: In fetal SBA, neuroepithelial/ependymal denudation in the telencephalon and the aqueduct can occur before Chiari II malformation and/or hydrocephalus. Since denuded areas cannot re-establish cell function, neuro-developmental consequences could induce permanent cerebral pathology.

Truncus arteriosus, a rare and complex congenital heart disease, is hallmarked by a single great vessel (truncus) that arises over a large ventricular septal defect and provides both the pulmonary and systemic circulation. Pregnancy reports after repair for truncus arteriosus are scarce. Therefore, the maternal and offspring outcomes are unknown. We report the outcome of a pregnancy in an 18-year-old woman with repaired truncus arteriosus. Despite severe and symptomatic deterioration of truncal valve regurgitation, she successfully delivered a healthy child, and the valve function recovered within 2 weeks postpartum., (Copyright 2007 S. Karger AG, Basel.)

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.

In this study, we investigated whether the Achilles tendon reflex (ATR) in healthy infants is modulated by changes in body position (prone vs. supine). The amplitude of the ATR was compared at postnatal day 1, months 2, 3 and 6, while infants were placed in prone and supine position. The ATR was considered "positive" when at least 1 of 20 tendon taps evoked a visible contraction of the ankle plantar flexor muscles. At 6 months, the amplitude and latency of the ATR were evaluated by electromyographic (EMG) recordings of the (lateral and medial) gastrocnemius muscle, with the infant in prone and supine position. At postnatal day 1, the clinical ATR response was more frequently present in prone than supine position (14/16 or 88% vs. 4/16 or 25%, respectively, p < 0.01). From 2 months onwards, the frequencies of positive ATRs were no longer significantly different between prone (14/14 or 100%) and supine position (10/14 or 67%). However, based on the EMG recordings at 6 months, the ATR amplitude was higher in prone compared to supine position (n=8, median 5.5 mV, range 4.7-6.6 mV; and median 3.8 mV, range 2.3-5.6 mV, p < 0.05). We conclude that the ATR response in healthy infants is more pronounced in prone than in supine position, either when clinically (visually) assessed during routine tendon tapping or when neurophysiologically assessed during surface EMG recording.

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.

Information on pregnancy and delivery in women with biventricular repair for isolated noncomplex pulmonary atresia with a ventricular septal defect (PAVSD) is limited. Using a nationwide congenital heart disease registry (CONgenital CORvitia [CONCOR]), 9 women with biventricular repair for PAVSD (aged 21 to 38 years) were identified. Ten pregnancies were observed in 5 different women with PAVSD, including 3 spontaneous miscarriages. Clinically significant (non)cardiac complications were documented in 3 of 7 completed pregnancies. These complications were: (1) atrioventricular reentry tachycardia with symptomatic right-sided heart failure; (2) eclampsia with hemolysis, elevated liver enzymes, and low platelets syndrome further complicated by abruptio placentae leading to premature delivery of a small-for-gestational-age child; and (3) premature delivery due to cervical insufficiency with antepartum demise of an immature child. Furthermore, none of the women reported infertility. Moreover, none of the women reported irregularities of their natural menstrual cycle (age at menarche 13 years; cycle duration 28 days), with the exception of delayed menarche (>16 years) in 2 patients. In conclusion, successful pregnancy in patients with biventricular repair of PAVSD is possible, although often complicated by serious clinically significant events. Infertility and menstrual cycle disorders do not appear to be more prevalent, except for a high incidence of primary amenorrhea.

The objective of the present study to investigate fertility, pregnancy, and delivery in women with biventricular repair for pulmonary atresia with an intact ventricular septum (PAIVS). Using a nationwide registry (CONCOR), 37 patients with pulmonary atresia were identified, 6 of whom (aged 21 to 34 years) had biventricular repair for PAIVS. Three PAIVS patients had a total of 5 pregnancies, including 1 abortion and 1 ectopic pregnancy. Besides minor noncardiac complications, the 3 live-birth pregnancies were successful. None of the women reported infertility or irregularities (hypermenorrhea, dysmenorrhea, polymenorrhoea, oligomenorrhea, or amenorrhea) of their natural menstrual cycle. In conclusion, successful pregnancy in women with biventricular repair for PAIVS is possible, and only minor complications were observed. Infertility and menstrual cycle disorders do not appear to be more prevalent than usual.

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.

Aims: To investigate magnitude and determinants of risks during pregnancy in women with Mustard or Senning repair for complete transposition of the great arteries (TGA)., Methods and Results: Using a nationwide registry (CONCOR), 70 women with Senning (23%) or Mustard (77%) repair for TGA were enrolled. A total of 28 patients had 69 pregnancies (two twins), including 17 spontaneous miscarriages and three elective abortions. During 39 of the 49 completed pregnancies, complications were observed. The most important cardiac complication was clinically significant arrhythmia (n=11, 22%), especially occurring in patients with a prior history of arrhythmia. Important general pregnancy complications were preeclampsia (n=5, 10.2%) and pregnancy-induced hypertension (n=4, 8.2%). Obstetric complications included premature rupture of membranes (n=7, 14.3%), premature labour (n=12, 24.4%), premature delivery (n=16, 31.4%), and thrombo-embolic complications (n=2, 4.1%). Mean (singleton) pregnancy duration was 36+/-5 weeks. Eleven of the 51 children (21.6%) were small for gestational age. Foetal and neonatal mortality combined was 11.8% (n=6). No recurrence of congenital heart disease in the offspring was documented., Conclusion: In this largest report on pregnancy in women with atrial-corrected TGA to date, a high incidence of obstetric complications and mortality in the offspring was observed.

Objective: In neonates with spina bifida aperta (SBA), leg movements innervated by spinal segments located caudal to the meningomyelocele are transiently present. This study in neonates with SBA aimed to determine whether the presence of leg movements indicates functional integrity of neuronal innervation and whether these leg movements disappear as a result of dysfunction of upper motor neurons (axons originating cranial to the meningomyelocele) and/or of lower motor neurons (located caudal to the meningomyelocele)., Methods: Leg movements were investigated in neonates with SBA at postnatal day 1 (n = 18) and day 7 (n = 10). Upper and lower motor neuron dysfunction was assessed by neurologic examination (n = 18; disinhibition or inhibition of reflexes, respectively) and by electromyography (n = 12; absence or presence of denervation potentials, respectively)., Results: Movements, related to spinal segments caudal to the meningomyelocele, were present in all neonates at postnatal day 1. At day 1, leg movements were associated with signs of both upper (10 of 18) and lower (17 of 18) motor neuron dysfunction caudal to the meningomyelocele. In 7 of 10 neonates restudied after the first postnatal week, leg movements had disappeared. The absence of leg movements coincided with loss of relevant reflexes, which had been present at day 1, indicating progression of lower motor neuron dysfunction., Conclusions: We conclude that the presence of neonatal leg movements does not indicate integrity of functional lower motor neuron innervation by spinal segments caudal to the meningomyelocele. Present observations could explain why fetal surgery at the level of the meningomyelocele does not prevent loss of leg movements.