Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

BACKGROUND: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. METHODS: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. RESULTS: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. CONCLUSIONS: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT03973359).

The cumulative incidence of neonatal metabolic acidemia after terminal bradycardia in the 2nd stage of labor: a survival-based model.

PURPOSE: The aim of the study was to estimate by a survival analysis model the hazard function (HF) for neonatal metabolic acidemia (MA) throughout the 2nd stage of labor (2STG) at the time of occurrence of a terminal bradycardia ≥ 10 min requiring expedited delivery, and the cumulative incidence function (CIF) for MA according with the duration of bradycardia stratified in 10-12 min and > 12 min. METHODS: Singleton pregnancies experiencing terminal fetal bradycardia requiring expedited delivery in the 2STG at 38 + 0-41 + 3 weeks and delivering in the year 2019, were identified. The presence of MA (pH < 7 and/or BE ≤ - 12 mmol/L) was determined based on the acid-base status in the umbilical artery cord blood. Survival analysis was used to assess the hazard function (HF) and the cumulative incidence function (CIF) for MA occurring after terminal fetal bradycardia, at the 2STG. RESULTS: Out of a non-consecutive population of 12,331 pregnancies, there were 52 cases that fit the inclusion criteria. Twenty-four (46.2%) of those develop MA. Abnormal quantitative pH values and the HF for MA correlated with the duration of 2STG at the time of bradycardia onset, but not with bradycardia duration. After 60 min of duration of 2STG, the HF (or instantaneous rate of failure) increased dramatically (from 1.2 to 20 about at 120 min). At paired duration of 2STG, a higher CIF was observed for the terminal bradycardia > 12 min. CONCLUSION: Forty-six percent of term fetuses with terminal bradycardia had MA at birth. Despite the low sensitivity and a non-significant association with quantitative pH values, the duration of terminal bradycardia in the 2STG is associated with a higher CIF for MA.

Obstetric, neonatal, and child health outcomes following embryo biopsy for preimplantation genetic testing.

BACKGROUND: Preimplantation genetic testing (PGT) of embryos developed in vitro requires a biopsy for obtaining cellular samples for the analysis. Signs of cell injury have been described in association with this procedure. Thus, the consequences of the biopsy on obstetric and neonatal outcomes have been the subject of some quantitative analyses, although the reliability of data pooling may be limited by important issues in the various reports. OBJECTIVE AND RATIONALE: The present review identifies evidence for whether pregnancies conceived after embryo biopsy are associated with a higher risk of adverse obstetric, neonatal, and long-term outcomes. Available evidence has been summarized considering manipulation at various stages of embryo development. SEARCH METHODS: We used the scoping review methodology. Searches of article databases were performed with keywords pertaining to the embryo biopsy technique and obstetric, neonatal, and postnatal outcomes. Studies in which embryos were biopsied at different stages (i.e. both at the cleavage and blastocyst stages) were excluded. We included data on fresh and frozen embryo transfers. The final sample of 31 documents was subjected to qualitative thematic analysis. OUTCOMES: Sound evidence is lacking to fully address the issues on the potential obstetric, neonatal or long-term consequences of embryo biopsy. For polar body biopsy, the literature is too scant to draw any conclusion. Some data, although limited and controversial, suggest a possible association of embryo biopsy at the cleavage stage with an increased risk of low birthweight and small for gestational age neonates compared to babies derived from non-biopsied embryos. An increase in preterm deliveries and birth defects in cases of trophectoderm biopsy was suggested. For both biopsy methods (at the cleavage and blastocyst stages), an increased risk for hypertensive disorders of pregnancy was found. However, these findings may be explained by confounders such as other embryo manipulation procedures or by intrinsic patient or population characteristics. WIDER IMPLICATIONS: Since there is inadequate evidence to assess obstetric, neonatal, and long-term health outcomes following embryo biopsy, an invasive PGT strategy should be developed with a cautious approach. A non-invasive approach, based on the analysis of embryo cell-free DNA, needs to be pursued to overcome the potential limitations of embryo biopsy.

Prenatal Diagnosis and Postnatal Outcomes of Left Brachiocephalic Vein Abnormalities: Systematic Review.

Abnormalities of the left brachiocephalic vein (LBCVA) are rare and poorly studied prenatally. An association with congenital heart defects (CHD), extracardiac and genetic abnormalities was described. The aim of our study was to estimate the rate and summarize the available evidence concerning prenatal diagnosis, associated anomalies, and outcomes of these anomalies. A systematic literature review was carried out selecting studies reporting on prenatal diagnosis of LBCVA, including unpublished cases from our experience. Frequencies were pooled from cohort studies to calculate prenatal incidence. Pooled proportions were obtained from all the studies including rates of associated CHD, extracardiac or genetic abnormalities and neonatal outcomes. The search resulted in the selection of 16 studies with 311 cases of LBCVA, with an incidence of 0.4% from six cohort studies. CHD occurred in 235/311 (75.6%) fetuses: 23 (7.4%) were major in cases of double, retroesophageal or subaortic course and 212 (68.2%) were minor in cases of absence (always associated with a persistent left superior vena cava) or intrathymic course. Data on other associated outcomes were scarce showing rare extracardiac anomalies (3.5%), rare genetic abnormalities (RASopathies and microdeletions associated with the retroesophageal course), and neonatal outcomes favorable in most cases, particularly in intrathymic forms.

IVF/ICSI treatment and the risk of iatrogenic preterm birth in singleton pregnancies: systematic review and meta-analysis of cohort studies.

OBJECTIVES: Preterm birth (PTB) is more frequent among in vitro fertilization (IVF) as compared to natural conception and recent research in this group describes an increase of its spontaneous etiology. However, clear description and quantification of iatrogenic preterm birth (IPTB) was not determined in IVF/ICSI (intra-cytoplasmic sperm injection) conceptions. This study quantifies the risk of IPTB in singleton pregnancies resulting from IVF/ICSI as compared to spontaneous conceptions (SCs). METHODS: Web-based databases search (PubMed/Medline, Scopus, Web of Science) from inception up to January 2019 looking for cohort studies comparing the risk of IPTB in singleton pregnancies obtained with IVF/ICSI (intervention group) or SC (control group). Only studies with clear distinction of spontaneous and indicated PTB were included. Primary outcome was IPTB before 37 weeks of gestation, defined as indicated delivery for any medical recommendation. All pertinent secondary outcomes were also included: IPTB <34/32/28 weeks, abnormal cardiotocography (CTG), abruptio, placenta previa, pre-eclampsia, fetal growth restriction, any other available indication to IPTB. A meta-analysis calculated the pooled odds ratio (OR) for IPTB in IVF/ICSI and SC, using random effects model. Sensitivity analysis for study quality, methodology of case counting, use of cryotransfer, and secondary analyses for available indications of IPTB were also performed. Prospero RN: CRD42019117672. RESULTS: Pooled crude analysis showed a sample size of 9590 births with significant increase in IPTB <37 weeks in IVF/ICSI pregnancies (nine studies, pooled proportion IPTB IVF/ICSI 4.73% vs. SC 1.81%; OR = 2.47; 95% CI: 1.46-4.18; I2 = 67%). Pooled analysis was impossible for most secondary outcomes due to lack of available data and failed to show statistical significance for abnormal CTG. The risk for IPTB due to abruptio placentae or placenta previa was significantly increased in IVF/ICSI pregnancies (two studies, 561 pregnancies; pooled proportion IPTB IVF/ICSI 2.12% vs. SC 1.06%; OR = 5.41; 95% CI: 1.26-23.25; I2: 0%). CONCLUSION: The risk of IPTB <37 weeks in singleton pregnancies achieved after IVF/ICSI is significantly greater than that occurring in SC. This is likely due to a multifactorial etiology, in which placental diseases are included. Full etiologic understanding of this association needs further clarification. SUMMARY: The risk of IPTB below 37 weeks in singleton pregnancies achieved after IVF/ICSI is more than double than that occurring in natural conception.

Greater fetal crown-rump length growth with the use of in vitro fertilization or intracytoplasmic sperm injection conceptions after thawed versus fresh blastocyst transfers: secondary analysis of a prospective cohort study.

OBJECTIVE: To compare first-trimester fetal crown-rump length (CRL) measurements in pregnancies obtained after thawed blastocyst transfer versus fresh blastocyst transfer after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). DESIGN: Prospective longitudinal cohort study of CRL Z scores with adjustment for major confounders. SETTING: University-affiliated obstetrics, fetal medicine, and fertility units. PATIENT(S): Singleton gestations conceived via IVF/ICSI and fresh or thawed blastocyst transfer with ultrasound performed at 6-14 weeks of gestational age. INTEVENTION: None. MAIN OUTCOME MEASURE(S): CRL Z scores. RESULT(S): A total of 365 IVF/ICSI pregnancies were recruited (fresh: 161; thawed: 204). The mean CRL Z score at 6-14 weeks was significantly greater in thawed versus fresh transfers. Different growth trajectories between thawed and fresh transfers were detected: Mean CRL Z score was 0 at 65 days in fresh versus 80 days in frozen. Comparisons of both fresh and thawed transfers with reference values from the general population confirmed significantly lower CRL Z scores in both IVF/ICSI groups (P<.001). The risks of CRL <5th percentile in fresh versus thawed were, respectively 68% vs. 40% at 6 weeks and 2% vs. 1% at 14 weeks. A significant positive correlation between CRL Z scores and birth weight Z scores was found only for fresh transfers, not for thawed. CONCLUSION(S): At 6-14 weeks, thawed blastocyst transfers after IVF/ICSI conceptions present greater CRLs compared with fresh, and both IVF/ICSI groups show smaller CRLs than the general population. This effect is particularly evident before 9 weeks and it may favor birth weight difference of thawed versus fresh BT pregnancies.

Prevalence of Congenital Heart Defects in Pregnancies Conceived by Assisted Reproductive Technology: A Cohort Study.

BACKGROUND AND AIM OF THE STUDY: Pregnancies obtained by assisted reproductive technology (ART) are associated with an increased risk of complications and congenital anomalies, particularly congenital heart defects (CHDs). Therefore, our aim is to evaluate, retrospectively, the prevalence of CHD in ART pregnancies in our two centers and analyze their characteristics and outcomes. METHODS: Observational study including fetuses conceived by ART referred between June 2011 and September 2020 and undergoing a fetal cardiac ultrasound scan. Cases with genetic, chromosomal abnormalities or extracardiac malformations were excluded. Population included 1511 pregnancies, which consisted of 269 twins and 1242 singletons, 547 IVF (in vitro fertilization), 773 ICSI (intracytoplasmic sperm injection) and 191 oocyte donations (OD). RESULTS: CHDs were found in 29 fetuses, with an overall prevalence of 1.92% (29/1511), 1.85% (23/1242) in singletons and 2.23% in twins (6/269). Thirteen were IVF, eight ICSI and eight OD cases, with a greater risk of CHD after IVF and OD (IVF: 13/29 (44.8%)-one twin; ICSI: 8/29 (27.6%)-three twins); 22 had major and 7 minor defects. Two pregnancies with a hypoplastic left heart were terminated; the majority of live-born cases needed surgery. Three babies died (two post-surgery, one had a late death). CONCLUSIONS: Our data show an increased prevalence of CHD after ART with a heterogeneous spectrum of diagnoses, mainly major defects.

Prenatal Management of Congenital Human Cytomegalovirus Infection in Seropositive Pregnant Patients Treated with Azathioprine.

Human cytomegalovirus (HCMV) is the leading infectious agent causing congenital disabilities. The risk of HCMV transmission to the fetus in pregnant women receiving immunosuppressive agents is unknown. We describe two cases of pregnant women with evidence of pre-conception HCMV protective immunity receiving azathioprine for ulcerative colitis or systemic lupus erythematosus. Both women reactivated the HCMV and transmitted the infection to the fetuses. One newborn showed unilateral hearing deficits and brain abnormalities while the other was asymptomatic. The mother of the symptomatic newborn had low levels of total and HCMV-specific blood CD4+ T cells. Women receiving immunosuppressive agents deserve information about the risk of HCMV congenital infection and should be monitored for HCMV infection during pregnancy. Their newborns should be screened for HCMV congenital infection.