Second- and third-trimester serum levels of growth-differentiation factor-15 in prediction of pre-eclampsia.

OBJECTIVE: Pre-eclampsia (PE) is a significant contributor to adverse maternal and perinatal outcome; however, accurate prediction and early diagnosis of this condition remain a challenge. The aim of this study was to compare serum levels of growth-differentiation factor-15 (GDF-15) at three different gestational ages between asymptomatic women who subsequently developed preterm or term PE and healthy controls. METHODS: This was a case-control study drawn from a prospective observational study on adverse pregnancy outcomes in women attending for their routine second- and third-trimester hospital visits. Serum GDF-15 was determined in 300 samples using a commercial GDF-15 enzyme-linked immunosorbent assay: 120 samples at 19-24 weeks of gestation, 120 samples at 30-34 weeks and 60 samples at 35-37 weeks. Multiple linear regression was applied to logarithmically transformed GDF-15 control values to evaluate the influence of gestational age at blood sampling and maternal characteristics on GDF-15 results. GDF-15 multiples of the normal median (MoM) values, adjusted for gestational age and maternal characteristics, were compared between pregnancies that subsequently developed preterm or term PE and healthy controls. RESULTS: Values of GDF-15 increased with gestational age. There were no significant differences in GDF-15 MoM values between cases of preterm or term PE and normotensive pregnancies at 19-24 or 35-37 weeks of gestation. At 30-34 weeks, GDF-15 MoM values were significantly increased in cases of preterm PE, but not in those who later developed term PE. Elevated GDF-15 MoM values were associated significantly with a shorter interval between sampling at 30-34 weeks and delivery with PE (P = 0.005). CONCLUSION: Serum GDF-15 levels at 19-24 or 35-37 weeks of gestation are not predictive of preterm or term PE. At 30-34 weeks, GDF-15 levels are higher in women who subsequently develop preterm PE; however, this difference is small and GDF-15 is unlikely to be useful in clinical practice when used in isolation. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Tissue Doppler imaging in fetuses with aortic stenosis and evolving hypoplastic left heart syndrome before and after fetal aortic valvuloplasty.

OBJECTIVES: Fetal aortic valvuloplasty can improve filling and reduce afterload of the left ventricle in critical aortic stenosis. Success of an intrauterine intervention is currently measured by technical success, clinical survival and eventual postnatal biventricular physiology. In the present study we investigated the use of tissue Doppler imaging (TDI) to evaluate changes in ventricular function assessed before and after prenatal aortic valvuloplasty. METHODS: Between October 2008 and December 2012, cardiac function was assessed by TDI before and after intervention in 23 fetuses that underwent technically successful valvuloplasty for critical aortic stenosis and in which postnatal outcome was known. The measurements were transformed into gestational age-independent Z-scores where appropriate. RESULTS: Mean ± SD gestational age at intervention was 27.5 ± 3.1 weeks. Of the 23 fetuses, 14 had biventricular outcome. Before intervention all left ventricular (LV) TDI-derived parameters and mitral annular plane systolic excursion (MAPSE) were severely abnormal. It was possible to demonstrate considerably improved cardiac function after technically successful valvuloplasty. Among fetuses with postnatal biventricular outcome, TDI-derived LV myocardial peak velocity during early diastole (E') and myocardial peak velocity during systole in the ejection phase (S') significantly increased, E'/myocardial peak velocity during late diastole with atrial contraction (A') increased towards normal values, and LV transmitral-to-mitral-annular diastolic velocity ratio (E/E') and myocardial performance index (MPI') decreased but remained abnormally elevated. In addition, right ventricular A', S' and MPI' significantly improved after intervention. CONCLUSION: Technically successful fetal aortic valvuloplasty led to significantly improved myocardial performance. It was possible to use TDI to detect distinct changes in ventricular function and TDI-derived parameters correlated with a biventricular outcome after birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Maternal aspects of fetal cardiac intervention.

OBJECTIVES: Fetal cardiac interventions have the potential to alter natural disease progression and reduce morbidity and mortality in children. Although there are already encouraging data on fetal outcome, information on maternal morbidity and mortality after intervention is scarce. The aim of the present study was to assess maternal aspects, pregnancy-associated risks and adverse events in 53 intrauterine cardiac interventions. METHODS: Between October 2000 and December 2012, 53 fetal cardiac interventions were performed in 47 patients (43 aortic valve dilations in 39 patients, seven pulmonary valve dilations in six patients and three balloon atrioseptostomies in two patients). Median gestational age was 26 + 4 (range, 20 + 3 to 33 + 1) weeks. Interventions were performed by an ultrasound-guided percutaneous approach under general anesthesia. All medical records and patient charts were analyzed retrospectively. RESULTS: All women were considered to be healthy in the preoperative assessment; 39 (83%) patients continued pregnancy until term and eight of 47 patients had an intrauterine fetal death (IUFD) and were induced. Postoperative nausea was reported in 29.8% of patients and abdominal pain in 36.2% of patients on the day of surgery. Preterm contractions were observed in two patients; no preterm prelabor rupture of membranes occurred. One severe postpartum hemorrhage was observed in a patient with IUFD and subsequent induction; however, this was unrelated to the balloon valvuloplasty. No intensive care unit admission and no major anesthesia-associated complications (aspiration, anaphylactic reaction, cardiovascular collapse, damage to teeth, laryngeal damage, awareness or hypoxic brain damage) were observed. Maternal mortality was zero. A significant learning curve was observed in terms of duration of intervention. CONCLUSION: In our experience, percutaneous needle-guided fetal cardiac intervention seems to be a safe procedure for the mother. In 53 procedures no major maternal complication directly related to the intervention was observed.

Prenatal diagnosis and outcome of absent pulmonary valve syndrome: contemporary single-center experience and review of the literature.

OBJECTIVE: To review the anomaly spectrum of prenatally detected absent pulmonary valve syndrome (APVS) and the outcome after diagnosis. Previous fetal studies reported survival rates of ≤ 25% for patients with intended postnatal care. METHODS: Clinical data and echocardiograms of 12 cases with a fetal diagnosis of APVS between 2000 and 2010 were analyzed in this retrospective single-center study. Collected parameters included: gestational age at referral, associated fetal abnormalities, cardiothoracic ratio, maximum diameters of pulmonary annulus and main and branch pulmonary arteries, ventricular dimensions and function as well as ventricular Doppler flows. Karyotyping included fluorescence in-situ hybridization (FISH) analysis for microdeletion 22q11.2. RESULTS: Median gestational age at diagnosis was 24 weeks. Three subtypes of APVS were observed: (1) with tetralogy of Fallot (TOF) and no arterial duct (n = 10; 83%); (2) isolated, with a large arterial duct (n = 1; 8%); and (3) with tricuspid atresia, right ventricular dysplasia and a restricted duct (n = 1; 8%). The cardiothoracic ratio and pulmonary artery dimensions were increased in all cases. The karyotype was abnormal in 70% of fetuses with TOF and their mortality rate was significantly higher due to pregnancy termination (n = 3) or perinatal demise (n = 2) (hazard ratio, 5; 95% CI, 0.87-28.9; P = 0.015). Of seven live births with active postnatal care, six children (86%) were alive without residual respiratory symptoms at a median follow-up of 4.7 (range, 2.1-10.6) years. CONCLUSION: Outcome after fetal diagnosis of APVS was significantly better in this study compared with those of previous fetal series, with a low mortality rate for actively managed patients.

[Closing gastroschisis: a distinct entity with high morbidity and mortality]. / Closing Gastroschisis: eine Sonderform der Gastroschisis mit hoher Morbidität und Mortalität.

PURPOSE: We correlate severe bowel damage in gastroschisis to the rare intrauterine event of narrowing of the abdominal wall around the protruding intestines. We describe this "closing gastroschisis" as a distinct entity. Prenatal ultrasound findings as gastric or bowel dilation were compared to the postnatal findings in order to find markers for an early in utero diagnosis of closing gastroschisis. Early diagnosis could prompt timely delivery to save the compromised bowel and avoid short gut syndrome. MATERIALS AND METHODS: We documented the pre- and postnatal course of our patients with gastroschisis from 2007 to 2009.  Closing gastroschisis was suspected antenatally and confirmed postnatally. We identified 5 out of 18 patients showing closure of the abdominal wall with varying degrees of bowel damage. Prenatal ultrasound findings were correlated to the postnatally confirmed extent of intestinal damage. RESULTS: We could not find consistent ultrasound markers for prenatal diagnosis of closing gastroschisis. In prenatal ultrasound three patients presented significant gastric dilation and then experienced severe courses postnatally due to segmental gut necrosis. One of these three died and the other two developed short gut syndrome. In one case progressive intraabdominal loop dilation with simultaneous shrinking of the extraabdominal loops occurred corresponding to closing gastroschisis with segmental midgut necrosis. CONCLUSION: Closing gastroschisis must be seen as a special form of gastroschisis. Extended intestinal damage is often life-threatening. In longitudinal observation dynamics of fetal ultrasound findings can lead to the diagnosis of closing gastroschisis. Progressive intraabdominal loop dilation is always highly suspicious and must lead to close follow-up and timely delivery.

[Effect of noninvasive first trimester diagnosis on indications and results of chorion villi sampling]. / Einfluss der nicht invasiven Ersttrimester-Diagnostik auf Indikationen und Ergebnisse der Chorionzottenbiopsien.

AIM: In this explorative study it should be evaluated how the introduction of non invasive first trimester diagnosis (nuchal translucency measurement, Combined Test, first trimester ultrasound screening) has influenced the indications and cytogenetic results of chorion villi samplings. MATERIALS AND METHODS: Between 1989 and 2008 3337 pregnancies with CVS between 11 and 14 weeks of gestation were examined retrospectively. They were divided in two groups: CVS 1989 - 2001 before introduction of non invasive first trimester diagnosis (n = 1698) and CVS 2002 - 2008 after introducing non invasive testing at the end of 2001 (n = 1639). In both groups the indications for CVS (maternal age, sonographic findings, past history, maternal anxiety, and abnormal results of the Combined Test only in the second group) and the cytogenetic results were evaluated. RESULTS: In the first group (1989 - 2001, n = 1698) 85,6% (n = 1454) of all CVS were performed because of maternal age and only 3% (n = 51) due to sonographic findings. In the second group (2002 - 2008, n = 1639) there was a distinct increase of sonographic findings leading to CVS (33,9%, n = 555) with a clear decrease of maternal age to 37,9% (n = 621). Abnormal cytogenetic results were found in 10,5% (n = 172) in the second group, in the first group only in 4,5% (n = 76), respectively. The parameter with the highest rate of chromosomal disorders was fetal hydrops (66,1%), follwed by hygroma colli (48,2%), malformations (12,9%) and increased nuchal translucency (11,2%). Regarding maternal age alone the rate of abnormal chromosomes was 3,1%. CONCLUSIONS: It could be shown that non invasive first trimester diagnosis has lead to a more specific indication for invasive fetal testing (sonographic findings 33,9 vs. 3%, maternal age 37,9 vs. 85,6%) with a higher rate of chromosomal disorder in this group (10,5 vs. 4,5%).

Intrauterine aortic valvuloplasty in fetuses with critical aortic stenosis: experience and results of 24 procedures.

OBJECTIVE: Valvuloplasty of the fetal aortic valve has the potential to prevent progression of critical aortic stenosis (AS) to hypoplastic left heart syndrome (HLHS). The aim of the study was to assess 24 aortic valvuloplasties regarding indications, success rate, procedure-related risks and outcome. METHODS: Between January 2001 and December 2009 we performed 24 aortic valvuloplasties in 23 fetuses with critical AS at a median gestational age of 26 + 4 (range, 21 + 3 to 32 + 5) weeks by a transabdominal ultrasound-guided approach. Four fetuses had hydrops as a late sign of heart failure. RESULTS: In 16/24 procedures (66.7%) corresponding to 16/23 fetuses (69.6%) the procedures were technically successful, with one intrauterine death in this group. After an initial learning curve, success rate improved to 78.6% (11 of the last 14 interventions were successful). In 10 out of the 15 (66.7%) successfully-treated and liveborn fetuses a biventricular circulation could be achieved postnatally. All four fetuses with hydrops had successful interventions, hydrops disappearing within 5 weeks. In 8/24 interventions (33.3%) the aortic valve could not be treated successfully, with intrauterine fetal death in two of these cases. In one fetus a repeat procedure was successful. All surviving fetuses with unsuccessful (n = 5) or no (n = 5) procedure performed developed HLHS until delivery. CONCLUSIONS: Fetal aortic valvuloplasty could be performed successfully in selected fetuses with critical AS and evolving HLHS, with a biventricular outcome in two thirds of the patients. Safety and success rate were dependent on patient selection and the level of experience of the whole interventional team. In fetuses with AS and hydrops, aortic valvuloplasty could reverse end-stage heart failure and hydrops and ensure fetal survival.

[Elective cesarean section--delivery mode of the future or social misconception?]. / Elektive Sectio--Geburtsmodus der Zukunft oder gesellschaftliche Fehlentwicklung?

Over the past 20 years, the rate of Cesarean section has undergone a marked increase on a global level and it appears unlikely that this trend will be reversed in the near future. This fact has also raised a number of questions regarding the growing preference for elective Cesarean section following a complication-free pregnancy and in the absence of medical indications. Both, the mortality rate of carefully prepared procedures of this kind, as well as the attending morbidity rate, have been successfully reduced in recent years owing to improvements in section technique, causing certain of the maternal and fetal risks accompanying vaginal delivery to come under closer scrutiny than before. The potential damage to the perineum during birth--and the impairment of the parturient's sexuality this may cause--in conjunction with the fact that vaginal delivery continues to expose the infant to certain risks which cannot be ruled out entirely, has made the choice between vaginal delivery and Cesarean section increasingly difficult. The argument most frequently cited in favour of vaginal delivery concerns the unimpaired birth experience it offers. Many women, however, do not consider this a high priority. In keeping with the greater importance currently being assigned to patients' preferences, the authors support the view that the parturient herself should be enabled to decide what level of risk is acceptable to her, including stating her preference for a delivery by Cesarean section. It cannot be stressed enough that, in this context, comprehensive information and rigorous documentation are indispensable requirements.