Historically, prenatal screening has focused primarily on the detection of fetal aneuploidies. Cell-free DNA now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2 deletion syndrome, large cohort studies with confirmatory postnatal testing to assess test performance have not been reported. This study aimed to assess the performance of single-nucleotide polymorphism-based, prenatal cell-free DNA screening for detection of 22q11.2 deletion syndrome. Patients who underwent single-nucleotide polymorphism-based prenatal cell-free DNA screening for 22q11.2 deletion syndrome were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation using chromosomal microarrays. The primary outcome was sensitivity, specificity, positive predictive value, and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are ≥500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2 deletion syndrome and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome. Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). A total of 12 22q11.2 deletion syndrome cases were confirmed in the cohort, including 5 (41.7%) nested deletions, yielding a prevalence of 1 in 1524. In the total cohort, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q11.2 deletion syndrome and 38 (0.2%) cases as high risk; 275 (1.5%) cases were nonreportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% confidence interval, 42.8-94.5); specificity of 99.84% (95% confidence interval, 99.77-99.89); positive predictive value of 23.7% (95% confidence interval, 11.44-40.24), and negative predictive value of 99.98% (95% confidence interval, 99.95-100). None of the cases with a nonreportable result was diagnosed with 22q11.2 deletion syndrome. The updated algorithm detected 10 of 12 cases (83.3%; 95% confidence interval, 51.6-97.9) with a lower false positive rate (0.05% vs 0.16%; P<.001) and a positive predictive value of 52.6% (10/19; 95% confidence interval, 28.9-75.6). Noninvasive cell-free DNA prenatal screening for 22q11.2 deletion syndrome can detect most affected cases, including smaller nested deletions, with a low false positive rate.

Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy. To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed. A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate. In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation.

Background: This report evaluates results of a screening program on prenatal detection of congenital heart defects in a geographical cohort of western Sweden between January 1st, 2013 and June 31st, 2017. During the study period 88,230 children were born in VGR. Methods: Retrospective data on pregnant women from the Västra Götaland region that were referred to fetal cardiologists in Gothenburg were retrieved. To determine prenatal detection rate, all neonates who underwent surgery or catheter intervention for a critical congenital heart defect born between January 1st, 2014 and December 31st, 2016 were included. The four-chamber view was implemented into the routine scan in 2009 and implementation of the ISUOG guidelines, including the outflow tracts, started in the region in 2015. Results: 113 fetuses received a prenatal diagnosis of a major congenital heart defect. 89% of these were referred because of a suspected cardiac malformation and 88% were diagnosed before 22 completed weeks. 59% of the patients diagnosed before 22 completed weeks opted for termination of pregnancy. During 2014–2016, 61 fetuses had a prenatal diagnosis of a critical congenital heart defect and a further 47 were diagnosed after birth, hence 56% were diagnosed prenatally, 82% for those which had a combination with an extracardiac abnormality and/or chromosomal aberration compared to 50% if an isolated critical congenital heart defect was diagnosed. For single ventricle cardiac defects such as hypoplastic left heart syndrome, double inlet left ventricle and tricuspid atresia, the detection rate was 100%. The detection rate for transposition of the great arteries and coarctation of the aorta was 9 and 18% respectively. Conclusions: 56% of all fetuses with a critical congenital heart defect were diagnosed prenatally during 2014–2016 and approximately 53% of all major congenital heart defects 2013–2017 as compared to 13.8% in 2009 in the same region. An increased focus towards the fetal heart in the routine scan improved the prenatal detection rate of major congenital heart defects. The detection of congenital heart defects affecting the four-chamber view seems sufficient, but more training is needed to improve the quality of the examination of the outflow tracts.

Hypoxia–ischemia (HI) injury in term infants develops with a delay during the recovery phase, opening up a therapeutic window after the insult. Hypothermia is currently an established neuroprotective treatment in newborns with neonatal encephalopathy (NE), saving one in nine infants from developing neurological deficits. Caspase-2 is an initiator caspase, a key enzyme in the route to destruction and, therefore, theoretically a potential target for a pharmaceutical strategy to prevent HI brain damage. The aim of this study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice–Vannucci model of HI injury in mice. HI brain injury was moderately reduced in caspase-2^−/− mice as compared with wild-type (WT) mice. Five hours of hypothermia (33 °C ) vs. normothermia (36 °C) directly after HI provided additive protection overall (temperature P = 0.0004, caspase-2 genotype P = 0.0029), in the hippocampus and thalamus, but not in other gray matter regions or white matter. Delayed hypothermia initiated 2 h after HI in combination with caspase-2 gene deficiency reduced injury in the hippocampus, but not in other brain areas. In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone.

Introduction: Three per cent of all infants are born in breech presentation, still the preferred way to deliver them remains controversial. The objective of this systematic review was to assess the safety for the mother and child depending on intended mode of delivery when the baby is in breech position at term.Material and Methods: The population (P) was pregnant women with a child in breech presentation, from gestational week 34⁺⁰. The intervention (I) was the intention to deliver by cesarean section, the comparison (C) was the intention to deliver vaginally. Outcomes (O) were perinatal mortality, perinatal morbidity, maternal mortality, maternal morbidity, conversion of delivery mode, and the mother's experience. Systematic literature searches were performed. We included randomized trials, cohort studies with more than 500 women/group and case series for more than 15 000 women published between 1990 and October 2021, written in English or the Nordic languages. The certainty of evidence was assessed using the GRADE approach and data were pooled in meta‐analyses. PROSPERO registration number: CRD42020209546.Results: Thirty‐two articles were included (with 530 604 women). The certainty of evidence was moderate or low because the study designs were mostly retrospective cohort studies. The only randomized trial showed reduced risk of perinatal mortality for planned cesarean section, risk ratio (RR) 0.27 (95% confidence interval [CI] 0.08–0.97, 2078 women, low certainty of evidence), stillbirths excluded. A meta‐analysis of cohort studies resulted in a similar estimate, RR 0.36 (95% CI 0.25–0.51, 21 studies, 388 714 women, low certainty of evidence). We also found reduced risk for outcomes representing perinatal morbidity 0–28 days: 5‐min Apgar score less than 7 in one randomized controlled trial: RR 0.27 (95% CI 0.12–0.58, 2033 women, moderate certainty of evidence), and in a meta‐analysis: RR 0.1 (95% CI 0.14–0.26, 18 studies, 217 024 women, moderate certainty of evidence); APGAR score less than 4 at 5 min: RR 0.39 (95% CI 0.19–0.81, five studies, 44 498 women, low certainty of evidence); and pH less than 7.0: RR 0.23 (95% CI 0.12–0.43, four studies, 13 440 women, low certainty of evidence). Outcomes for the mother were similar in the groups except for reduced risk for experience of urinary incontinence in the group of planned cesarean section: RR 0.62 (95% CI 0.41–0.93, one study, 1940 women, low certainty of evidence). The conversion rate from planned vaginal delivery to emergency cesarean section ranged from 16% to 51% (median 41.8%, 10 studies, 50 763 women, moderate certainty of evidence).Conclusions: Intended cesarean section may reduce the risk of perinatal mortality and perinatal as well as some maternal morbidity compared with intended vaginal delivery. It is uncertain whether there is any difference in maternal mortality. The conversion rate from intended vaginal delivery to emergency cesarean section is high.

Introduction: Uterus transplantation (UTx) is a treatment for absolute uterine factor infertility. The results of pregnancies of this complex infertility treatment should be established. The aim of the study was to systematically review maternal and neonatal outcomes in the pregnancies of women who have undergone UTx.Material and Methods: The population of this review were women that have undergone UTx and delivered child(ren). Cesarean delivery after UTx were planned to be compared with studies reporting maternal mortality/morbidity and perinatal mortality/morbidity after delivery by elective cesarean section without UTx. Systematic literature searches were performed utilizing Medline, Embase, the Cochrane Library, Cinahl, PsycInfo, Web of Science, and clinicaltrials.gov for studies written in English language and published between January 1, 2010, and November 08, 2023. No study design limitation was applied. If no comparative studies were identified, we planned to report the outcomes from the case reports and case series. Included studies were assessed for risk of bias using a checklist for case series. The study protocol was registered with the International Platform of Registered Systematic Review and Meta‐analysis Protocols (registration number: INPLASY202310052).Results: Twenty‐four articles were identified, containing data on 40 unique live births. Multiple publications including same cases were identified and clearly indicated. No comparative studies were identified. The certainty of evidence was very low, as all studies were either case reports (n = 15) or case series (n = 9). All deliveries were by cesarean section and 47.5% of them resulted in emergency cesarean sections. Out of the 21 elective cesarean sections, 52.4% were performed before 37 weeks' gestation. Historical comparison to population data on pregnancies delivered by cesarean section found a markedly increased risk for both the mother and child following cesarean section for UTx. Risks for placenta previa and preterm birth were notably high after UTx; however, some of the later may reflect the results of provider‐initiated births.Conclusions: The maternal and perinatal outcomes of 40 live births post‐UTx indicate that these pregnancies may be at high risk of maternal and perinatal complications. Aiming to delay elective cesarean section beyond 37 weeks' gestation could potentially reduce some of these risks. Registration of maternal and perinatal outcomes after UTx through quality registries are essential and obstetrical care guidelines for these women should be established.