Weight discordance and perinatal mortality in twin pregnancy: systematic review and meta‐analysis

Objectives The primary aim of this systematic review was to explore the strength of association between birth‐weight (BW) discordance and perinatal mortality in twin pregnancy. The secondary aim was to ascertain the contribution of gestational age and growth restriction in predicting mortality in growth‐discordant twins. Methods MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched. Only studies reporting on the risk of mortality in twin pregnancies affected compared with those not affected by BW discordance were included. The primary outcomes explored were incidence of intrauterine death (IUD), neonatal death (NND) and perinatal death. Outcome was assessed separately for monochorionic (MC) and dichorionic (DC) twin pregnancies. Analyses were stratified according to BW discordance cut‐off (≥ 15%, ≥ 20%, ≥ 25% and ≥ 30%) and selected gestational characteristics, including incidence of IUD or NND before and after 34 weeks' gestation, presence of at least one small‐for‐gestational age (SGA) fetus in the twin pair and both twins being appropriate‐for‐gestational age. Risk of mortality in the larger vs smaller twin was also assessed. Meta‐analyses using individual data random‐effects logistic regression and meta‐analyses of proportion were used to analyze the data. Results Twenty‐two studies (10 877 twin pregnancies) were included in the analysis. In DC pregnancies, a higher risk of IUD, but not of NND, was observed in twins with BW discordance ≥ 15% (odds ratio (OR) 9.8, 95% CI, 3.9–29.4), ≥ 20% (OR 7.0, 95% CI, 4.15–11.8), ≥ 25% (OR 17.4, 95% CI, 8.3–36.7) and ≥ 30% (OR 22.9, 95% CI, 10.2–51.6) compared with those without weight discordance. For each cut‐off of BW discordance explored in DC pregnancies, the smaller twin was at higher risk of mortality compared with the larger one. In MC twin pregnancies, excluding cases affected by twin–twin transfusion syndrome, twins with BW discordance ≥ 20% (OR 2.8, 95% CI, 1.3–5.8) or ≥ 25% (OR 3.2, 95% CI, 1.5–6.7) were at higher risk of IUD, compared with controls. MC pregnancies with ≥ 25% weight discordance were also at increased risk of NND (OR 4.66, 95% CI, 1.8–12.4) compared with those with concordant weight. The risk of IUD was higher when considering discordant pregnancies involving at least one SGA fetus. The overall risk of mortality in MC pregnancies was similar between the smaller and larger twin, except in those with BW discordance ≥ 20%. Conclusion DC and MC twin pregnancies discordant for fetal growth are at higher risk of IUD but not of NND compared with pregnancies with concordant BW. The risk of IUD in BW‐discordant DC and MC twins is higher when at least one fetus is SGA

Current use and performance of the different fetal growth charts in the Italian population

Objectives: The choice of growth charts impacts on screening, diagnosis and clinical management of fetal growth abnormalities. The objectives of the study were to evaluate: 1) the clinical practice at a national level among tertiary referral centers in the use of fetal biometric growth charts; and 2) the impact on fetal growth screening of existing national and international growth charts. Study design: A questionnaire was sent to 14 Italian tertiary referral centers to explore biometric reference growth charts used in clinical practice. National and international (Intergrowth-21st and World Health Organization) fetal growth charts were tested on a large national cohort of low risk women with singleton uneventful pregnancy derived from a retrospective cross-sectional multicenter study (21 centers). The percentage of fetuses with biometric measurements below and above the 10th and 90th percentile for each biometric parameter and gestational week were calculated for each growth chart. The percentile curves of the study population were calculated by non-linear quantile regressions. Results: Twelve Italian centers (86 %) answered to the questionnaire showing a wide discrepancy in the use of growth charts for fetal biometry. The cohort included 7347 pregnant women. By applying Intergrowth-21st growth charts the percentage of fetuses with head circumference, abdominal circumference and femur length below the 10th centile was 3.9 %, 3.6 % and 2.3 %, and above the 90th centile 29.9 %, 32.5 % and 46 %, respectively. The percentages for the World Health Organization growth charts for head and abdominal circumferences and femur length were: below the 10th centile 6.3 %, 7.2 % and 5.3 %, and above 90th centile 22.8 %, 21.3 % and 31.9 %, respectively. Conclusions: The wide discrepancy in clinical use of fetal growth charts in Italian centers warrants the adoption of an uniform set of charts. Our data suggest that immediate application into clinical practice of international growth charts might result into an under-diagnosis of small for gestational age fetuses and, especially, in an over-diagnosis of large for gestational age fetuses with major consequences for clinical practice. On these grounds, there is an urgent need for a nationwide study for the prospective evaluation of international growth charts and, if needed, the construction and adoption of methodologically robust national growth charts

Obliterated cavum septi pellucidi: Clinical significance and role of fetal magnetic resonance

Introduction: The objective of this study was to describe a cohort of fetuses with an ultrasound prenatal diagnosis of obliterated cavum septi pellucidi (oCSP) with the aim to explore the rate of associated malformations, the progression during pregnancy and the role of fetal magnetic resonance imaging (MRI).Material and methods: This was a retrospective multicenter international study of fetuses diagnosed with oCSP in the second trimester with available fetal MRI and subsequent ultrasound and/or fetal MRI follow-up in the third trimester. Where available, postnatal data were collected to obtain information on neurodevelopment.Results: We identified 45 fetuses with oCSP at 20.5 weeks (interquartile range 20.1-21.1). oCSP was apparently isolated at ultrasound in 89% (40/45) and fetal MRI found additional findings in 5% (2/40) of cases, including polymicrogyria and microencephaly. In the remaining 38 fetuses, fetal MRI found a variable amount of fluid in CSP in 74% (28/38) and no fluid in 26% (10/38). Ultrasound follow-up at or after 30 weeks confirmed the diagnosis of oCSP in 32% (12/38) while fluid was visible in 68% (26/38). At follow-up MRI, performed in eight pregnancies, there were periventricular cysts and delayed sulcation with persistent oCSP in one case. Among the remaining cases with normal follow-up ultrasound and fetal MRI findings, the postnatal outcome was normal in 89% of cases (33/37) and abnormal in 11% (4/37): two with isolated speech delay, and two with neurodevelopmental delay secondary to postnatal diagnosis of Noonan syndrome at 5 years in one case and microcephaly with delayed cortical maturation at 5 months in the other.Conclusions: Apparently isolated oCSP at mid-pregnancy is a transient finding with the visualization of the fluid later in pregnancy in up to 70% of cases. At referral, associated defects can be found in around 11% of cases at ultrasound and 8% at fetal MRI indicating the need for a detailed evaluation by expert physicians when oCSP is suspected

Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: when timing matters

Stress exposure during pregnancy is critically linked with maternal mental health and child development. The effects might involve altered patterns of DNA methylation in specific stress-related genes (i.e., glucocorticoid receptor gene, NR3C1, and serotonin transporter gene, SLC6A4) and might be moderated by the gestational timing of stress exposure. In this study, we report on NR3C1 and SLC6A4 methylation status in Italian mothers and infants who were exposed to the COVID-19 pandemic lockdown during different trimesters of pregnancy. From May 2020 to February 2021, 283 mother–infant dyads were enrolled at delivery. Within 24 h from delivery, buccal cells were collected to assess NR3C1 (44 CpG sites) and SLC6A4 (13 CpG sites) methylation status. Principal component (PC) analyses were used to reduce methylation data dimension to one PC per maternal and infant gene methylation. Mother–infant dyads were split into three groups based on the pregnancy trimester (first, second, third), during which they were exposed to the COVID-19 lockdown. Mothers and infants who were exposed to the lockdown during the first trimester of pregnancy had lower NR3C1 and SLC6A4 methylation when compared to counterparts exposed during the second or third trimesters. The effect remained significant after controlling for confounders. Women who were pregnant during the pandemic and their infants might present altered epigenetic biomarkers of stress-related genes. As these epigenetic marks have been previously linked with a heightened risk of maternal psychiatric problems and less-than-optimal child development, mothers and infants should be adequately monitored for psychological health during and after the pandemic

Is Brain-Derived Neurotropic Factor Methylation Involved in the Association Between Prenatal Stress and Maternal Postnatal Anxiety During the COVID-19 Pandemic?

BackgroundThe COVID-19 pandemic is a collective trauma that may expose susceptible individuals to high levels of stress. Pregnant women represent a high-risk population, considering that pregnancy is a period of heightened neuroplasticity and susceptibility to stress through epigenetic mechanisms. Previous studies showed that the methylation status of the BDNF gene is linked with prenatal stress exposure. The goals of this study were (a) to assess the association between pandemic-related stress and postnatal anxiety and (b) to investigate the potential role of maternal BDNF methylation as a significant mediator of this association. MethodsIn the present study, we report data on the association among pandemic-related stress during pregnancy, maternal BDNF methylation, and postnatal anxiety symptoms. Pandemic-related stress and postnatal anxiety were assessed through self-report instruments. BDNF methylation was estimated in 11 CpG sites in DNA from mothers' buccal cells. Complete data were available from 108 mothers. ResultsResults showed that pandemic-related stress was associated with an increased risk of postnatal anxiety, r = 0.20, p < 0.05. CpG-specific BDNF methylation was significantly associated with both prenatal pandemic-related stress, r = 0.21, p < 0.05, and postnatal maternal anxious symptoms, r = 0.25, p = 0.01. Moreover, a complete mediation by the BDNF CpG6 methylation emerged between pandemic-related stress during pregnancy and postnatal maternal anxiety, ACME = 0.66, p < 0.05. ConclusionThese findings suggest that BDNF epigenetic regulation by pandemic-related stress might contribute to increase the risk of anxiety in mothers. Policymakers should prioritize the promotion of health and wellbeing in pregnant women and mothers during the present healthcare emergency

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

Vaccination against SARS-CoV-2 in pregnancy during the Omicron wave: the prospective cohort study of the Italian obstetric surveillance system

Objectives: Evidence on the effects of the SARS-CoV-2 Omicron variant on vaccinated and unvaccinated pregnant women is sparse. This study aimed to compare maternal and perinatal outcomes of women infected with SARS-CoV-2 during the Omicron wave in Italy, according to their vaccine protection.Methods: This national prospective cohort study enrolled pregnant women with a positive SARS-CoV-2 nasopharyngeal swab within 7 days of hospital admission between 1 January and 31 May, 2022. Women who received at least one dose of vaccine during pregnancy and those who completed the vaccine cycle with the first booster were considered protected against moderate or severe COVID-19 (MSCD). A multivariable logistic regression model evaluated the association between vaccine protection and disease severity. Maternal age, educational level, citizenship, area of birth, previous comorbidities, and obesity were analysed as potential risk factors. Results: MSCD was rare (41/2147, 1.9%; 95% CI, 1.4-2.6), and the odds of developing it were significantly higher among unprotected women (OR, 2.78; 95% CI, 1.39-5.57). Compared with protected women (n = 1069), the unprotected (n = 1078) were more often younger, with lower educational degrees, and foreigners. A higher probability of MSCD was found among women with previous comorbidities (OR, 2.86; 95% CI, 1.34-6.12) and those born in Asian countries (OR, 3.05; 95% CI, 1.23-7.56). The percentage of preterm birth was higher among women with MSCD compared with milder cases (32.0% [8/25] versus 8.4% [161/1917], p < 0.001) as well as the percentage of caesarean section (52.0% [13/25] versus 31.6% [606/1919], p 0.029). Discussion: Although severe maternal and perinatal outcomes were rare, their prevalence was significantly higher among women without vaccine protection. Vaccination during pregnancy has the potential to protect both the mother and the baby, and it is therefore strongly recommended. Edoardo Corsi Decenti, Clin Microbiol Infect 2023;29:772 (c) 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved