Early Mortality in Infants Born with Neonatally Operated Congenital Heart Defects and Low or Very-Low Birthweight: A Systematic Review and Meta-Analysis.

Mortality outcomes of children with isolated neonatally operated congenital heart defects (CHDs) born with a low (LBW), moderately low (MLBW) or very-low birthweight (VLBW) remain ambiguous. We searched Medline and Embase (inception until October 2021) and included studies that evaluated early mortality. The risk of bias was assessed using the Critical Appraisal Skills Program cohort checklist. Meta-analysis involved random-effects models. We explored variability in mortality across birthweight subgroups, CHD types, and study designs. From 2035 reports, we included 23 studies in qualitative synthesis, and the meta-analysis included 11 studies (1658 CHD cases), divided into 30 subcohorts. The risk of bias was low in 4/11 studies included in the meta-analysis. Summary mortality before discharge or within one month after surgery was 37% (95%CI 27-47). Early mortality varied by birthweight (VLBW 56%, MLBW 15%, LBW 16%; p = 0.003) and CHD types (hypoplastic left heart syndrome (HLHS) 50%, total anomalous pulmonary venous return (TAPVR) 47%, transposition of the great arteries (TGA) 34%, coarctation of the aorta (CoA) 16%; p = 0.13). Mortality was higher in population-based studies (49% vs. 10%; p = 0.006). One-third of infants born with neonatally operated isolated CHDs and LBW, MLBW, or VLBW died within 30 days after surgery. Mortality varied across infant and study characteristics. These results may help clinicians assess neonatal prognosis. PROSPERO registration CRD42020170289.

Tranexamic acid for the prevention of blood loss after cesarean among women with twins: a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery randomized clinical trial.

BACKGROUND: Although prophylactic tranexamic acid administration after cesarean delivery resulted in a lower incidence of calculated estimated blood loss of >1000 mL or red cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies. OBJECTIVE: This study aimed to compare the effect of tranexamic acid vs placebo to prevent blood loss after cesarean delivery among women with multiple pregnancies. STUDY DESIGN: This was a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial data, a double-blind, randomized controlled trial from March 2018 to January 2020 in 27 French maternity hospitals, that included 319 women with multiple pregnancies. Women with a cesarean delivery before or during labor at ≥34 weeks of gestation were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss of >1000 mL or a red blood cell transfusion by 2 days after delivery. The secondary outcomes included clinical and laboratory blood loss measurements. RESULTS: Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, and 298 (93.4%) had primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% confidence interval, 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P>.05 for all comparisons). CONCLUSION: Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.

Arabin pessary to prevent adverse perinatal outcomes in twin pregnancies with a short cervix: a multicenter randomized controlled trial (PESSARONE).

BACKGROUND: The number of twin pregnancies continues to increase worldwide as both the number of pregnancies obtained by medically assisted reproduction and age at first pregnancy keep rising. Preterm delivery is the major complication associated with twin pregnancies. The effectiveness of preventive treatments such as progesterone or cervical cerclage for women with a short cervix is doubtful in twin pregnancies. The effectivity of cervical pessaries in preventing preterm birth and its associated morbidity and mortality is also controversial. OBJECTIVE: We sought to investigate if the Arabin pessary reduces adverse neonatal outcomes in twin pregnancies with a short cervix. STUDY DESIGN: This open-label, multicenter, randomized controlled trial on twin pregnancies with a cervical length of <35 mm compared pessary placement at 16+0 to 24+0 weeks' gestation with standard care alone. The primary endpoint was a composite of adverse neonatal outcomes, namely peripartum or neonatal death or significant neonatal morbidity before hospital discharge, defined as at least 1 of the following complications: bronchopulmonary dysplasia, intraventricular hemorrhage grade III to IV, periventricular leukomalacia, necrotizing enterocolitis grade II or higher, culture-proven sepsis, and retinopathy requiring treatment. A sample size of 308 pregnancies was planned to ensure 80% power to compare the proportions of women with at least 1 infant with an adverse neonatal outcome. The intention-to-treat analysis after multiple imputation of missing data, was supplemented with a secondary analysis that controlled for gestational age and cervical length, both at inclusion. The primary endpoint was also compared between randomization groups in the per-protocol population, which excluded patients with prespecified major protocol violations (mostly cervical cerclage and/or progesterone after inclusion). Secondary endpoints included preterm birth, spontaneous preterm birth, and pessary side effects. RESULTS: In total, 315 women were randomized to either receive a pessary (n=157) or standard management (n=158). Overall, 10.8% (34 women) of participants had a missing value for the primary endpoint, mostly (79%) because of the lack of paternal consent for neonatal data collection. In the intention-to-treat analysis, the adverse neonatal outcome occurred in 16.8% of the pessary group vs in 22.5% of the control group (risk ratio, 0.69; 95% confidence interval, 0.39-1.23; P=.210). The per-protocol analysis did not show any significant difference between groups (risk ratio, 0.78; 95% confidence interval, 0.47-1.28; P=.320). The occurrence of preterm birth or spontaneous preterm birth did not differ significantly between groups. No serious side effects were associated with pessary use. CONCLUSION: Pessary use in our study did not significantly reduce adverse neonatal outcomes in twin pregnancies with a short cervix.

Predicting Factors of Protracted Intestinal Failure in Children with Gastroschisis.

OBJECTIVE: To identify prenatal and neonatal predictors of short bowel syndrome-related intestinal failure (SBS-IF) in gastroschisis. STUDY DESIGN: This retrospective study included all patients with gastroschisis born between 2000 and 2017 who were enrolled in our home parenteral nutrition program, and all patients with gastroschisis born in our institution who survived 2 weeks, during the same time period. Prenatal ultrasound features, neonatal status, anatomic features, oral feeding, and parenteral nutrition dependency were analyzed. RESULTS: Among 180 patients, 35 required long-term parenteral nutrition (SBS-IF group) and 145 acquired full oral feeding within 6 months (oral feeding group). The mean follow-up was 7.9 years (IQR, 1.6-17.5 years) and 5.0 years (IQR, 0.1-18.2 years), respectively. Both bowel matting (OR, 14.23; 1.07-16.7; P = .039) and secondarily diagnosed atresia or stenosis (OR, 17.78; 3.13-100.98; P = .001) were independent postnatal predictors of SBS-IF. Eighteen children (51% of the SBS-IF group) were still dependent on artificial nutrition at the last follow-up. patients with SBS-IF who achieved full oral feeding had a median residual small-bowel length of 74 cm (IQR, 51-160 cm) vs 44 cm (IQR, 10-105 cm) for those still dependent on artificial nutrition (P = .02). An initial residual small bowel length of more than 50 cm was the best predictive cut-off for nutritional autonomy, with a sensitivity of 67% and a specificity of 100%. CONCLUSIONS: Bowel matting, complex gastroschisis, and secondary intestinal obstruction were associated with SBS-IF in gastroschisis. For patients with SBS-IF, a small bowel length of more than 50 cm was predictive of secondary nutritional autonomy.

Glial Periorbital Heterotopia: A Rare Type of Ocular Mass.

Congenital orbital masses are rare disorders. A wide variety of lesions, including malignant and benign tumors, may develop around the orbit; hemangioma, lymphangioma, and optic nerve meningioma are the most common. Counseling for the prognosis and postnatal treatment depends on antenatal suspicion. Glial heterotopia should also be considered for the differential diagnosis. Integration of antenatal ultrasound and magnetic resonance imaging characteristics could help in the differential diagnosis. For the first time to our knowledge, a literature review on fetal orbital tumors was performed, along with a systematic description of imaging characteristics, treatment, and the prognosis.

The use of fetal MRI for renal and urogenital tract anomalies.

Fetal anomalies are detected in approximately 2% of all fetuses and, among these, genitourinary tract abnormalities account for 30% to 50% of all structural anomalies present at birth. Although ultrasound remains the first line diagnostic modality, fetal MRI provides important additional structural and functional information, especially with the development of faster sequences and the use of functional sequences. The added value of MRI-based imaging is three-fold: (a) improvement of diagnostic accuracy by adequate morphological examination, (b) detection of additional anomalies, and (c) in addition, MRI has the potential to provide information regarding renal function. In this review, we describe the role of fetal MRI in the anatomical evaluation of renal and urogenital tract anomalies, and we also touch upon the contribution of functional MRI to the diagnostic workup of these conditions.

Fetal Cystoscopy and Vesicoamniotic Shunting in Lower Urinary Tract Obstruction: Long-Term Outcome and Current Technical Limitations.

BACKGROUND: In utero therapeutic approaches for lower urinary tract obstruction (LUTO) have been developed to salvage the fetal kidney function. OBJECTIVE: The aim of this work was to report the long-term survival, nephrological, and urological outcome of children treated prenatally for LUTO using operative fetal cystoscopy (FC) and vesicoamniotic shunting (VAS) or both. METHODS: A retrospective study of 48 procedures (23 FC, 25 VAS) was performed on 33 patients (between 2008 and 2018). Reviewed data included prenatal management and clinical follow-up by a pediatric nephrologist and a pediatric urologist. Both intention-to-treat and per-protocol analyses were conducted. RESULTS: The median follow-up was 3.6 years (0.5-7) for FC and 2.5 years (1.1-5.1) for VAS. There was no difference between FC and VAS in terms of survival (92 vs. 83%, p = 1), complication rate (74 vs. 92%, p = 0.88), or chronic kidney disease (58 vs. 50%, p = 1). The number of procedures was higher in the VAS group: 1.7 (1-3) versus 1.1 (1-2), p = 0.01. With a 30% rate of technical failure, FC added diagnostic value in 3 out of 21 cases. CONCLUSIONS: No difference was found between FC and VAS regarding survival, long-term kidney function, or urological outcome. Despite overly optimistic reports on FC, it lacks reproducibility due to posterior-urethra inadequate visualization and inappropriate instrumentation.

Placental MRI and its application to fetal intervention.

OBJECTIVE: Magnetic resonance imaging (MRI) of placental invasion has been part of clinical practice for many years. The possibility of being better able to assess placental vascularization and function using MRI has multiple potential applications. This review summarises up-to-date research on placental function using different MRI modalities. METHOD: We discuss how combinations of these MRI techniques have much to contribute to fetal conditions amenable for therapy such as singletons at high risk for fetal growth restriction (FGR) and monochorionic twin pregnancies for planning surgery and counselling for selective growth restriction and transfusion conditions. RESULTS: The whole placenta can easily be visualized on MRI, with a clear boundary against the amniotic fluid, and a less clear placental-uterine boundary. Contrasts such as diffusion weighted imaging, relaxometry, blood oxygenation level dependent MRI and flow and metabolite measurement by dynamic contrast enhanced MRI, arterial spin labeling, or spectroscopic techniques are contributing to our wider understanding of placental function. CONCLUSION: The future of placental MRI is exciting, with the increasing availability of multiple contrasts and new models that will boost the capability of MRI to measure oxygen saturation and placental exchange, enabling examination of placental function in complicated pregnancies.

The use of image fusion in prenatal medicine.

Fusion imaging (FI), the simultaneous display of the same anatomical region using two imaging modalities, has been used in other areas of medicine for both diagnosis and guiding interventions. Examples include positron emission tomography-computed tomography (PET-CT) imaging in oncology and ultrasound-magnetic resonance imaging (US-MRI) fusion in biopsies of the prostate gland. The underlying principle is to take advantage of the complementary information in each modality to improve accuracy, be it diagnostic accuracy or targeting accuracy in biopsies. For example, PET-CT overlays the metabolic activity of lesions on the superb spatial and anatomical detail of CT. While the historical mainstay of fetal imaging has been ultrasound, advances in ultrafast MR imaging together with advances in fetal MRI over the past two decades, have resulted in the opportunity to explore fusion imaging in fetal medicine. We present an overview of the principles of US-MRI fusion imaging in prenatal medicine, report our local experience, and review the literature in this emerging area. We share our perspective on how FI can improve diagnostic confidence, be used as an educational tool, and potentially enhance guidance in certain fetal procedures.

Recurrent RTTN mutation leading to severe microcephaly, polymicrogyria and growth restriction.

Autosomal recessive missense Rotatin (RTTN) mutations are responsible for syndromic forms of malformation of cortical development, ranging from isolated polymicrogyria to microcephaly associated with primordial dwarfism and other major malformations. We identified, by trio based whole exome sequencing, a homozygous missense mutation in the RTTN gene (c.2953A > G; p.(Arg985Gly)) in one Moroccan patient from a consanguineous family. The patient showed early onset primary microcephaly, detected in the fetal period, postnatal growth restriction, encephalopathy with hyperkinetic movement disorders and self-injurious behavior with sleep disturbance. Brain MRI showed an extensive dysgyria associated with nodular heterotopia, large interhemispheric arachnoid cyst and corpus callosum hypoplasia.

Effect of Cell-Free DNA Screening vs Direct Invasive Diagnosis on Miscarriage Rates in Women With Pregnancies at High Risk of Trisomy 21: A Randomized Clinical Trial.

Importance: Cell-free DNA (cfDNA) tests are increasingly being offered to women in the first trimester of pregnancies at a high risk of trisomy 21 to decrease the number of required invasive fetal karyotyping procedures and their associated miscarriages. The effect of this strategy has not been evaluated. Objective: To compare the rates of miscarriage following invasive procedures only in the case of positive cfDNA test results vs immediate invasive testing procedures (amniocentesis or chorionic villus sampling) in women with pregnancies at high risk of trisomy 21 as identified by first-trimester combined screening. Design, Setting, and Participants: Randomized clinical trial conducted from April 8, 2014, to April 7, 2016, in 57 centers in France among 2111 women with pregnancies with a risk of trisomy 21 between 1 in 5 and 1 in 250 following combined first-trimester screening. Interventions: Patients were randomized to receive either cfDNA testing followed by invasive testing procedures only when cfDNA tests results were positive (n = 1034) or to receive immediate invasive testing procedures (n = 1017). The cfDNA testing was performed using an in-house validated method based on next-generation sequencing. Main Outcomes and Measures: The primary outcome was number of miscarriages before 24 weeks' gestation. Secondary outcomes included cfDNA testing detection rate for trisomy 21. The primary outcome underwent 1-sided testing; secondary outcomes underwent 2-sided testing. Results: Among 2051 women who were randomized and analyzed (mean age, 36.3 [SD, 5.0] years), 1997 (97.4%) completed the trial. The miscarriage rate was not significantly different between groups at 8 (0.8%) vs 8 (0.8%), for a risk difference of -0.03% (1-sided 95% CI, -0.68% to ∞; P = .47). The cfDNA detection rate for trisomy 21 was 100% (95% CI, 87.2%-100%). Conclusions and Relevance: Among women with pregnancies at high risk of trisomy 21, offering cfDNA screening, followed by invasive testing if cfDNA test results were positive, compared with invasive testing procedures alone, did not result in a significant reduction in miscarriage before 24 weeks. The study may have been underpowered to detect clinically important differences in miscarriage rates. Trial Registration: ClinicalTrials.gov Identifier: NCT02127515.

Impact of laser therapy for twin-to-twin transfusion syndrome on subsequent pregnancy.

OBJECTIVES: The objective of our study was to determine the impact of laser therapy for twin-to-twin transfusion syndrome (TTTs) on subsequent pregnancies. METHODS: This was a monocentric retrospective observational study. Women treated by laser fetoscopy for TTTs were asked to answer a postal questionnaire about subsequent pregnancies. The primary outcome was fecundity (number of pregnancies and time to pregnancy). We also assessed pregnancy complications, birth weight, and gestational age at delivery. Pregnancy complications included the following: threatened preterm labor, preeclampsia, placenta accreta, postpartum hemorrhage, and psychological disorders. Our study population was compared with an external control group made up of mothers of monochorionic twins without TTTs. RESULTS: We included 122 cases managed at the Necker Hospital between 2008 and 2012 and 39 controls. The median conception time was longer in the TTTs group (6.4 ± 11.1 versus 2 ± 1.6 months, P = .03). The numbers of live childbirths at the end of those pregnancies were equivalent (77.6% versus 66.7%, P = .56). Birth weight (3317 ± 726 versus 3240 ± 382 g, P = .81) and gestational age at delivery (38.2 ± 6.8 WG versus 39.5 ± 1.2 WG, P = .64) were similar, with no increase of obstetrical complications compared with the control group. DISCUSSION: Twin-to-twin transfusion syndrome and its treatment do not seem to impact subsequent pregnancies.

Segmental volvulus in the neonate: A particular clinical entity.

BACKGROUND: Complete intestinal volvulus is mainly related to congenital anomalies of the so-called intestinal malrotation, whereas segmental volvulus appears as a distinct entity, mostly observed during the perinatal period. Because these two situations are still lumped together, the aim of this study was to describe the particular condition of neonatal segmental volvulus. STUDY DESIGN: We analyzed the circumstances of diagnosis and management of 17 consecutives neonates operated for segmental volvulus more than a 10-year period in a single institution. During the same period, 19 cases of neonatal complete midgut volvulus were operated. RESULTS: Prenatal US exam anomalies were observed in 16/17 (94%) of segmental volvulus, significantly more frequently than in complete volvulus (p=0.003). Intestinal malposition was described peroperatively in all cases of complete volvulus, but also in 4/17 segmental volvulus (23%). Intestinal resection was performed in 88% of segmental volvulus when only one extensive intestinal necrosis was observed in complete volvulus. Parenteral nutrition was required in all patients with segmental volvulus with a median duration of 50days (range 5-251). CONCLUSION: Segmental volvulus occurs mainly prenatally and leads to fetal ultrasound anomalies. This situation, despite a limited length of intestinal loss, is associated to significant postnatal morbidity. TYPE OF THE STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.

Prenatal diagnosis of intra-abdominal cystic lesions by fetal ultrasonography: diagnostic agreement between prenatal and postnatal diagnosis.

OBJECTIVE: The aim of this study was to assess the diagnostic agreement between the prenatal diagnosis of intra-abdominal cystic lesions made by ultrasound examination and the postnatal diagnosis. METHODS: We reviewed all consecutive cases referred for an anechoic abdominal cyst from 2009 to 2013. Prenatal ultrasound diagnosis was compared with postnatal diagnosis. Prenatal diagnosis was defined as 'correct' if a specific prenatal diagnosis or one of the possible diagnoses was confirmed postnatally, as 'not confirmed' if the postnatal examination revealed no abnormalities and as 'incorrect' if the postnatal diagnosis was different from those suggested prenatally. RESULTS: Seventy-three cases were included, and prenatal diagnoses were made at a median gestational age of 27 weeks (range: 13-36). Correct diagnoses were made in 66 cases (90.4%), including four in which the lesion resolved spontaneously in utero; two diagnoses were 'not confirmed' postnatally, and one was incorrect (a prenatal diagnosis of intestinal duplication was in fact an anorectal malformation). Postnatal diagnosis was not achieved in four cases: None of them required surgery, and clinical follow-up was favorable. The abdominal cysts were isolated in 52 cases (71%) and associated with other anomalies in 21 cases (29%). Aneuploidies were diagnosed in three cases (all trisomy 21). Eight cases underwent termination of pregnancy; there were no fetal deaths and one neonatal death. Postnatal surgery was performed in 30 out of 65 liveborn infants (46.1%). CONCLUSION: Overall diagnostic agreement between prenatal and postnatal diagnosis of fetal intra-abdominal cystic lesions is high.

First-trimester combined screening for trisomy 21 in women with renal disease.

OBJECTIVE: To evaluate the results of first-trimester combined screening for Down syndrome in women with chronic renal disease. METHOD: Fifty-five pregnant women with renal disease were compared with 110 patients matched for maternal age, maternal weight, smoking status, and gestational age. Maternal renal function was assayed at the time of the combined screening, and renal insufficiency was defined by serum creatinine >90 µmol/L and renal clearance <80 mL/min. We defined three groups: kidney disease and normal renal function (group 1), kidney disease and renal insufficiency (group 2), and a control group (group 3). The values of nuchal translucency, pregnancy-associated plasma protein A, human ß-chorionic gonadotrophin (hCGß), and false-positive rates for Down syndrome screening were compared. RESULTS: There were 39 (71%) and 16 (29%) cases in groups 1 and 2, respectively. Nuchal translucency and multiple of the median (MoM) pregnancy-associated plasma protein A were similar in the three groups. However, MoM hCGß levels were higher in group 2 than in groups 1 and 3 (5.37 vs 1.1 vs 0.98 MoM, p = 0.0001). The resulting screen-positive rate was also higher in group 2 than in groups 1 and 3 (43.7% vs 10.2% vs 5.5%, p = 0.0001). CONCLUSION: Trisomy 21 first-trimester screening using hCGß is not suitable in the case of maternal renal failure. © 2014 John Wiley & Sons, Ltd.

Neonatal outcomes of prenatally diagnosed congenital pulmonary malformations.

BACKGROUND AND OBJECTIVE: Congenital pulmonary malformations (CPM) are mostly recognized on prenatal ultrasound scans. In a minority of cases, they may impair breathing at birth. The factors predictive of neonatal respiratory distress are not well defined, but an understanding of these factors is essential for decisions concerning the need for the delivery to take place in a tertiary care center. The aim of this study was to identify potential predictors of respiratory distress in neonates with CPM. METHODS: We selected cases of prenatal diagnosis of hyperechoic and/or cystic lung lesions from RespiRare, the French prospective multicenter registry for liveborn children with rare respiratory diseases (2008-2013). Prenatal parameters were correlated with neonatal respiratory outcome. RESULTS: Data were analyzed for 89 children, 22 (25%) of whom had abnormal breathing at birth. Severe respiratory distress, requiring oxygen supplementation or ventilatory support, was observed in 12 neonates (13%). Respiratory distress at birth was significantly associated with the following prenatal parameters: mediastinal shift (P = .0003), polyhydramnios (P = .05), ascites (P = .0005), maximum prenatal malformation area (P = .001), and maximum congenital pulmonary malformation volume ratio (CVR) (P = .001). Severe respiratory distress, requiring oxygen at birth, was best predicted by polyhydramnios, ascites, or a CVR >0.84. CONCLUSIONS: CVR >0.84, polyhydramnios, and ascites increased the risk of respiratory complications at birth in fetuses with CPM, and especially of severe respiratory distress, requiring oxygen supplementation or more intensive intervention. In such situations, the delivery should take place in a tertiary care center.

Cutaneous location of atypical teratoid/rhabdoid tumour.

Atypical teratoid/rhabdoid tumour is a rare and highly malignant tumour of the posterior fossae nervous system that occurs in children especially in the first few years of life. Cutaneous location is not previously reported. A newborn boy was referred for both aqueductal stenosis detected antenatally and skin tags mimicking hamartoma. The cerebral tumour increased in size during a few months leading to both skin and cerebral biopsies. Integrase Interactor-1 (INI-1) immunostaining and tumoural and leukocytes INI-1 gene sequencing confirmed the atypical teratoid/rhabdoid tumour nature of the cerebral tumour. INI-1 immunostaining in skin biopsy confirmed the dermal location of rhabdoid tumour. Thus, unusual cutaneous lesions may be part of atypical teratoid/rhabdoid tumour. The loss of Integrase INI-1 on immunohistochemical staining is characteristic.

Combined screening for open spina bifida at 11-13 weeks using fetal biparietal diameter and maternal serum markers.

OBJECTIVE: Screening at 11-13 weeks with ultrasound biparietal diameter (BPD) can detect half of open spina bifida cases. Maternal serum α-fetoprotein (AFP) levels at 15-19 weeks are increased 3- to 4-fold, in open spina bifida. We assessed whether combined screening using BPD, AFP, and other serum markers at 11-13 weeks would increase detection. STUDY DESIGN: Maternal AFP levels were measured on serum stored at 11-13 weeks in 44 open spina bifida and 182 unaffected pregnancies, and results were expressed in multiples of the median (MoM) for gestational age. All samples had been measured for free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein (PAPP)-A. A multivariate Gaussian model was used to predict screening performance from the serum data and BPD measurements on 80 cases, including 36 previously published. RESULTS: The median AFP level in cases was 1.201 MoM, significantly higher than in unaffected pregnancies (P < .01, 1 tail). The median free ß-hCG was significantly reduced to 0.820 MoM (P < .02), but the median PAPP-A was similar in cases and controls. Modeling predicted the following: BPD alone would detect 50% of cases for a 5% false-positive rate or 63% for 10%; adding AFP increases detection by 2%; and a combined test with BPD, AFP, and free ß-hCG detects 58% for 5% or 70% for 10%. CONCLUSION: Combining AFP and BPD with free ß-hCG as part of first-trimester aneuploidy screening would also allow early detection about two-thirds of cases with open spina bifida.

Fetal serum α-1 microglobulin for renal function assessment: comparison with ß2-microglobulin and cystatin C.

OBJECTIVE: To compare the prognostic value of fetal serum α1-microglobulin with that of ß2-microglobulin and cystatin C for postnatal renal function. METHOD: Retrospective study of α1-microglobulin, ß2-microglobulin, and cystatin C in fetal serum from 126 fetuses with congenital abnormalities of the kidney and urinary tract (73 and 53, respectively). Two groups were defined: group with normal renal function and group with renal failure. For live born infants, renal function was assessed on the basis of serum creatinine (cutoff 50 µmol/L) or glomerular filtration rate (cutoff 75 mL/min/1.73 m2) or both. In case of infant or fetal death, histological kidney lesions were considered. RESULTS: Significant differences (p < 0.001) were observed for the three markers between fetuses with good renal prognosis and those with renal failure (34.4 mg/L vs 67.6 mg/L for α1-microglobulin, respectively; 3.9 mg/L vs 7.35 mg/L, for ß2-microglobulin, respectively; and 1.67 mg/L vs 2.12 mg/L for cystatin C, respectively). Areas under receiver operator curves were used to compare the three markers, 0.96, 0.90, and 0.74 for ß2-microglobulin, α1-microglobulin, and cystatin C, respectively. CONCLUSION: Although α1-microglobulin is significantly different in fetuses with good renal prognosis and those with renal failure, overall, it is a less reliable prognostic marker than fetal serum ß2-microglobulin.