Risk factors for shunting at 12 months following open fetal repair of spina bifida by mini-hysterotomy.

OBJECTIVES: Open spina bifida (OSB) is the most common neural tube defect. Prenatal repair reduces the need for ventriculoperitoneal shunting (VPS) due to hydrocephalus from 80-90% to 40-50%. We aimed to determine which variables work as risk factors for VPS at 12 months of age in our population. METHODS: Thirty-nine patients underwent prenatal repair of OSB by mini-hysterotomy. The main outcome was occurrence of VPS in the first 12 months of life. Logistic regression was used to estimate the odds ratios (OR) between prenatal variables and the need for shunting. RESULTS: VPS at 12 months occurred in 34.2% of the children. Larger ventricle size before surgery (62.5% ≥15 mm; 46.2% between 12 and 15 mm; 11.8% <12 mm; p=0.008), higher lesion level (80% >L2, vs. 17.9% ≤L3; p=0.002; OR, 18.4 [2.96-114.30]), and later gestational age at surgery (25.25 ± 1.18 vs. 24.37 ± 1.06 weeks; p=0.036; OR, 2.23 [1.05-4.74]) were related to increased need for shunting. In the multivariate analysis, larger ventricle size before surgery (≥15 mm vs. <12 mm; p=0.046; OR, 1.35 [1.01-1.82]) and higher lesion level (>L2 vs. ≤L3; p=0.004; OR, 39.52 [3.25-480.69]) were risk factors for shunting. CONCLUSIONS: Larger ventricle size before surgery (≥15 mm) and higher lesion level (>L2) are independent risk factors for VPS at 12 months of age in fetuses undergoing prenatal repair of OSB by mini-hysterotomy in the studied population.

Association between preterm births and socioeconomic development: analysis of national data.

BACKGROUND: The increasing prevalence of preterm birth, which is a global phenomenon, is attributable to the increased medical indications, artificial gestations, and some socioeconomic factors. This study was conducted to identify whether development and equality indices are associated with the incidence of preterm birth, specifically, spontaneous and elective preterm births. METHODS: This retrospective observational study comprised an analysis of data on live births from 2019 in Brazil and on socioeconomic indices that were derived from census information in 2017. Data were summarised using absolute and relative frequencies. Spearman's correlation was used to determine the correlation between socioeconomic factors and the preterm birth rate. Multiple beta regression analysis was performed to determine the best model of socioeconomic covariates and preterm birth rate. The significance level was set at 5%. RESULTS: In 2019 in Brazil, the preterm birth rate was 11.03%, of which 58% and 42% were spontaneous and elective deliveries, respectively. For all preterm births, Spearman's correlation varied from ρ = 0.4 for the Gini Index and ρ = - 0.24 for illiteracy. The best fit modelled the spontaneous preterm birth fraction as a negative function of the Human Development Index (HDI). The best-fit model considered the expected elective preterm birth fraction as a positive function of the HDI and as a negative function of the Gini Index, which was used as a precision parameter. CONCLUSIONS: We observed a reduction in the fraction of spontaneous preterm births; however, the distribution was not uniform in the territory: higher rates of spontaneous preterm birth were noticed in the north, northeast, and mid-west regions. Thus, areas with lower education levels and inequal income distribution have a higher proportion of spontaneous preterm birth. The fraction of elective preterm birth was positively associated with more advantaged indices of socioeconomic status.

Sonographic evaluation of umbilical cord thickness in monochorionic diamniotic twin pregnancies.

OBJECTIVE: To develop a nomogram of the thickness of the umbilical cord (UC) and its components in monochorionic diamniotic (MCDA) twin pregnancies. METHODS: This prospective longitudinal study involved 47 MCDA twin pregnancies (94 fetuses) between 18 and 33 weeks of gestation. Ultrasound assessments of UC cross-sections and measurements of the umbilical cord area (UCA), the umbilical vein area (UVA), the umbilical artery area (UAA), and the Wharton jelly area (WJA) were made. The UC measurements were correlated with gestational ages. Reference values for the gestational ages of MCDA pregnancies were determined and compared with those of dichorionic twins and singletons. The cases which developed selective intrauterine growth restriction were contrasted with normal cases. RESULTS: A positive correlation was found between all UC components and gestational age and fetal weight. The UCA of MCDA fetuses was significantly larger than that of DC fetuses (p < 0.001) at the expense of a larger WJA (p < 0.001) and similar to that of singleton pregnancies. The MCDA fetuses with an estimated fetal weight below the 10th percentile had a smaller UCA than fetuses with a normal estimated weight (p < 0.001). CONCLUSION: The MCDA twins exhibited a thicker UC than that of dichorionic twins.

Open fetal myelomeningocele repair at a university hospital: surgery and pregnancy outcomes.

PURPOSE: Myelomeningocele (MMC) is an open neural tube defect that causes great morbidity. Prenatal open repair is the standard treatment; however, there are many complications related to the procedure. This study reports preliminary findings of open in utero repair of MMC in a public tertiary hospital in Brazil and describes factors that could be associated with increased surgical morbidity. METHODS: Thirty-nine patients underwent open in utero repair of MMC from October 2015 to August 2019. The Clavien-Dindo classification of surgical complications and a classification system with the preterm definitions of the World Health Organization were used, respectively, for maternal and fetal complications. RESULTS: A total of 28 mothers (71.8%) and 31 fetuses (79.5%) experienced at least one minor to major complication. Three mothers (7.7%) had a severe grade 4 complication. Fetal complications grades 3 to 5 occurred in 13 fetuses (33.3%). Gestational age at surgery and at birth were 24.88 ± 1.16 weeks and 33.23 ± 3.68 weeks, respectively. Preterm delivery occurred in 30 patients (76.9%), membrane rupture in 18 patients (46.2%) and chorioamnionitis in 13 patients (33.3%). CONCLUSION: Open fetal surgery for MMC was performed at a Brazilian public tertiary care center, resulting in three grade 4 maternal complications. Relevant fetal complications were also present. The use of a standard classification system for complications renders studies more comparable and data more useful for counseling patients. Adjustments of perioperative procedures and long-term follow-up are needed to determine the real benefit of open in utero repair of MMC at our hospital.

Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases.

Rare diseases comprise a diverse group of conditions, most of which involve genetic causes. We describe the variable spectrum of findings and clinical impacts of exome sequencing (ES) in a cohort of 500 patients with rare diseases. In total, 164 primary findings were reported in 158 patients, representing an overall diagnostic yield of 31.6%. Most of the findings (61.6%) corresponded to autosomal dominant conditions, followed by autosomal recessive (25.6%) and X-linked (12.8%) conditions. These patients harbored 195 variants, among which 43.6% are novel in the literature. The rate of molecular diagnosis was considerably higher for prenatal samples (67%; 4/6), younger children (44%; 24/55), consanguinity (50%; 3/6), gastrointestinal/liver disease (44%; 16/36) and syndromic/malformative conditions (41%; 72/175). For 15.6% of the cohort patients, we observed a direct potential for the redirection of care with targeted therapy, tumor screening, medication adjustment and monitoring for disease-specific complications. Secondary findings were reported in 37 patients (7.4%). Based on cost-effectiveness studies in the literature, we speculate that the reports of secondary findings may influence an increase of 123.2 years in the life expectancy for our cohort, or 0.246 years/cohort patient. ES is a powerful method to identify the molecular bases of monogenic disorders and redirect clinical care.

Isochromosome 21q is overrepresented among false-negative cell-free DNA prenatal screening results involving Down syndrome.

False-negative cell-free DNA (cfDNA) screening results involving Down syndrome are rare, but have high clinical impact on patients and their healthcare providers. Understanding the biology behind these results may allow for improved diagnostic follow-up and counseling. In 5 different centers offering cfDNA prenatal screening, 9 false-negative results were documented in 646 confirmed cases of trisomy 21; a false-negative rate of 1.4% (95% CI, 0.7-2.6). False-negative results included 4 cases of classical trisomy 21 and 5 cases with a de novo 21q;21q rearrangement. Two out of five rearrangements had molecular studies and were confirmed as isochromosomes. When combined with reports from the cfDNA screening literature, 8 out of 29 (28%) Down syndrome cases with a false-negative "non-invasive prenatal test" (NIPT) were associated with a 21q;21q rearrangement, compared with 2% reported in live born children with Down syndrome. In our laboratory series, evidence for placental or fetal mosaicism was present in 3 out of 3 true-positive cases involving a 21q;21q rearrangement and was confirmed in one false-negative case where placental material was available for study. Isochromosome 21q rearrangements are thus overrepresented among false-negative cfDNA screening results involving Down syndrome. Postzygotic isochromosome formation leading to placental mosaicism provides a biological cause for the increased prevalence of these rearrangements among false-negative cases. For clinical practice, a low trisomic fraction (z-score or equivalent measure) relative to the fetal fraction suggests placental mosaicism. Care should be taken as these cases may not reflect confined placental mosaicism, but rather full trisomy in the presence of a placenta containing normal cells.

Validation of QF-PCR for prenatal diagnoses in a Brazilian population.

OBJECTIVES:: Quantitative fluorescence polymerase chain reaction (QF-PCR) is a rapid and reliable method for screening aneuploidies, but in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory. METHOD:: A ChromoQuant QF-PCR kit containing 24 primer pairs targeting loci on chromosomes 21, 13, 18, X and Y was employed to identify aneuploidies of the referred chromosomes. RESULTS:: A total of 162 amniotic fluid samples analyzed using multiplex QF-PCR were compared with karyotyping analysis. The QF-PCR results were consistent with the results of cytogenetic analysis in 95.4% of all samples. CONCLUSION:: QF-PCR was demonstrated to be efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method. However, rearrangements and some mosaic samples cannot be detected with this test; thus, those exceptions must undergo cytogenetic analysis.

Validation of QF-PCR for prenatal diagnoses in a Brazilian population

OBJECTIVES: Quantitative fluorescence polymerase chain reaction (QF-PCR) is a rapid and reliable method for screening aneuploidies, but in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory. METHOD: A ChromoQuant QF-PCR kit containing 24 primer pairs targeting loci on chromosomes 21, 13, 18, X and Y was employed to identify aneuploidies of the referred chromosomes. RESULTS: A total of 162 amniotic fluid samples analyzed using multiplex QF-PCR were compared with karyotyping analysis. The QF-PCR results were consistent with the results of cytogenetic analysis in 95.4% of all samples. CONCLUSION: QF-PCR was demonstrated to be efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method. However, rearrangements and some mosaic samples cannot be detected with this test; thus, those exceptions must undergo cytogenetic analysis.

Placental weight and birth weight to placental weight ratio in monochorionic and dichorionic growth-restricted and non-growth-restricted twins.

OBJECTIVE:: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS:: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS:: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65) and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162) placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022) and dichorionic (p<0.001) twins compared to non-intrauterine growth-restricted twins. There was no difference in the birth weight/placental weight ratio between the intrauterine growth restriction and non-intrauterine growth restriction groups for either monochorionic (p=0.36) or dichorionic (p=0.68) twins. Placental weight and the birth weight/placental weight ratio were not associated with cord insertion type or with placental lesions. CONCLUSION:: Low placental weight, and consequently reduced functional mass, appears to be involved in fetal growth restriction in monochorionic and dichorionic twins. The mechanism by which low placental weight influences the birth weight/placental weight ratio in intrauterine growth-restricted monochorionic and dichorionic twins needs to be determined in larger prospective studies.

Placental weight and birth weight to placental weight ratio in monochorionic and dichorionic growth-restricted and non-growth-restricted twins

OBJECTIVE: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65) and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162) placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022) and dichorionic (p<0.001) twins compared to non-intrauterine growth-restricted twins. There was no difference in the birth weight/placental weight ratio between the intrauterine growth restriction and non-intrauterine growth restriction groups for either monochorionic (p=0.36) or dichorionic (p=0.68) twins. Placental weight and the birth weight/placental weight ratio were not associated with cord insertion type or with placental lesions. CONCLUSION: Low placental weight, and consequently reduced functional mass, appears to be involved in fetal growth restriction in monochorionic and dichorionic twins. The mechanism by which low placental weight influences the birth weight/placental weight ratio in intrauterine growth-restricted monochorionic and dichorionic twins needs to be determined in larger prospective studies.

[Can genital infections alter the results of preterm birth predictive tests?]. / As infecções genitais podem alterar os resultados dos testes preditivos do parto prematuro?

PURPOSE: To determine if the presence of infectious agents in vaginal or cervical content can alter the results of the insulin-like growth factor binding protein-1 (phIGFBP-1) test and the measurement of cervical length (CC) by transvaginal ultrasonography. METHODS: A total of 107 pregnant women with a history of spontaneous preterm birth were submitted to the phIGFBP-1 test and to measurement of CC by transvaginal ultrasonography every 3 weeks, between 24 and 34 weeks of gestation. Genital infections were determined immediately before testing. The patients were distributed into four groups (GA, GB, GC, and GD) and the correlation between genital infection and changes in the tests was determined within each group based on the odds ratio (OR) and the Pearson correlation coefficient. RESULTS: In each group, over 50% of the patients had genital infections (GA 10/17; GB 28/42; GC 15/24; GD 35/53), with bacterial vaginosis being the main alteration of the vaginal flora. Positive results for phIGFBP-1(GA 10/10; GB 18/28; GC 15/15; GD 19/35) and CC ≤ 20 mm (GA 10/10; GB 20/28; GC 10/15; GD 20/35) were obtained more frequently in patients with genital infection in all groups. Nonetheless, when applying the Pearson correlation coefficient we detected a poor correlation between genital infection and positivity for markers. CONCLUSION: The presence of changes in the vaginal flora and of other genital infections does not significantly alter the results of phIGFBP-1 and the measurement of cervical length when compared to cases without infection. However, more studies with larger samples are necessary to confirm these results.

[Preterm birth prediction: sequential evaluation of the cervix and the test for phosphorylated protein-1 linked to insulin-like growth factor]. / Predição do parto prematuro: avaliação sequencial do colo uterino e do teste para proteína-1 fosforilada ligada ao fator de crescimento insulina-símile.

PURPOSE: To investigate the usefulness of the measurement of cervical length and of the test for phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) performed sequentially in the prediction of preterm birth and the correlation between tests. METHODS: We analyzed data from 101 asymptomatic pregnant women with a history of premature delivery. The ultrasound measurement of cervical length and phIGFBP-1 test were performed in parallel every three weeks, between 24 and 34 week. The best cutoff value for each cervical evaluation was established by the ROC curve, and the two tests were compared using nonparametric tests. We determined the sensitivity, specificity and predictive values of each test and of the association of the exams for the occurrence of delivery before the 37th weeks. RESULTS: There were 25 preterm births (24.8%). The cervix length showed the highest sensitivity and was able to predict preterm birth in all evaluations, with similar accuracy at different gestational ages. The test for phIGFBP-1 was not helpful at 24 weeks, but was able to predict prematurity when performed at 27, 30 and 33 weeks. The combination of tests increased the sensitivity (81.8%) and negative predictive value (93.7%) when compared to the separate use of each test. The mean cervical length was lower in women with a positive test. CONCLUSIONS: Both cervical length and the test for phIGFBP-1 were able to predict premature delivery, and sequential combination of both tests showed a high sensitivity and high negative predictive value.

Ultrasound detection rate of single umbilical artery in the first trimester of pregnancy.

OBJECTIVE: To determine accuracy of first trimester detection of single umbilical artery (SUA). METHODS: The number of vessels in the umbilical cord was examined in a prospective cohort of 779 singleton, low-risk, unselected pregnancies, in the first (11-13 weeks) and second (17-24 weeks) trimesters, using both power and color Doppler and after delivery, by placental histopathologic exam. Concordance between first and second trimester findings to postnatal diagnoses was compared by calculating kappa coefficients. RESULTS: There was medium concordance between the findings in the first trimester and the postnatal diagnoses (kappa = 0.52) and high concordance (kappa = 0.89) for the second trimester scan. Sensitivity, specificity, positive and negative predictive values for the findings in the first trimester were 57.1, 98.9, 50.0 and 99.2% and for the second trimester were 86.6, 99.9, 92.9 and 99.7%. CONCLUSION: Sensitivity and positive predictive value of first trimester scan to identify an isolated SUA in a prospective unselected population was poor. Diagnosis of isolated SUA as well as a definitive judgment about the presence of associated anomalies would still require a scan in the second trimester.

Prediction of preterm delivery in the second trimester.

OBJECTIVE: The aim of this study was to estimate the probability of spontaneous delivery at 34 weeks or less according to cervical assessment by transvaginal scan associated with previous obstetric history. METHODS: Ultrasound transvaginal cervical length and presence of funneling were evaluated in 1,958 singleton pregnancies between 21 and 24 weeks of gestation. For the prediction of preterm delivery, the results of cervical assessment were analyzed in association with the previous obstetric history of preterm delivery, spontaneous miscarriage, and curettage. Sensitivity, specificity, and positive and negative predictive values for the various cutoff cervical lengths in the groups with or without previous history of preterm delivery were calculated. Multivariable regression analysis was used to identify the predictive factors for preterm delivery at 34 weeks or less. RESULTS: The incidence of spontaneous delivery at gestational age of 34 weeks or less was 3.4%. The mean cervical length was 30.1 mm (standard deviation 10.1 mm) in the group with previous history of prematurity (n = 180) and 35.8 mm (standard deviation 7.9 mm) in the group without previous history of prematurity (P < .001). The mean cervical length in the group of patients who delivered at or before 34 weeks was 23.8 mm, and for patients who delivered after 34 weeks it was 35.6 mm (P < .001). The mean gestational age at delivery was significantly lower in the group with funneling compared with the group without funneling (33.5 weeks versus 38.8 weeks, P < .001). Logistic regression analysis demonstrated that cervical length, funneling, and history of previous preterm delivery were independent contributors for preterm delivery. CONCLUSION: Ultrasound cervical assessment may be useful in the prediction of preterm delivery, but it should also be considered in association with the obstetric history of prematurity.