•A later gestational age at delivery impact positively the transplacental transfer ratio of neutralizing antibodies against SARS-CoV-2.•A longer delay from infection to delivery impact positively the ...transplacental transfer ratio of neutralizing antibodies against SARS-CoV-2.•Carrying a male fetus impact negatively the transplacental transfer ratio of neutralizing antibodies against SARS-CoV-2.•Transplacental transfer of antibodies following natural infection or vaccination might be different.
Due to immaturity of their immune system, passive maternal immunization is essential for newborns during their first months of life. Therefore, in the current context of intense circulation of SARS-CoV-2, identifying factors influencing the transfer ratio (TR) of neutralizing antibodies against SARS-CoV-2 (NAb) appears important.
Our study nested in the COVIPREG cohort (NCT04355234), included mothers who had a SARS-CoV-2 PCR positive during their pregnancy and their newborns. Maternal and neonatal NAb levels were measured with the automated iFlash system.
For the 173 mother-infant pairs included in our study, the median gestational age (GA) at delivery was 39.4 weeks of gestation (WG), and 29.7 WG at maternal SARS-CoV-2 infection. Using a multivariate logistic model, having a NAb TR above 1 was positively associated with a longer delay from maternal positive SARS-CoV-2 PCR to delivery (aOR 1.09, 95% CI: 1.03 – 1.17) and with a later GA at delivery (aOR = 1.58, 95% CI: 1.09 – 2.52). It was negatively associated with being a male newborn (aOR 0.21, 95% CI: 0.07 – 0.59). In 3rd trimester SARS-CoV-2 infected mothers, NAb TR was inferior to VZV, toxoplasmosis, CMV, measle and rubella‘s TR. However, in 1st or 2nd trimester infected mothers, only measle TR was different from NAb TR.
Male newborn of mothers infected by SARS-CoV-2 during their pregnancy appear to have less protection against SARS-CoV-2 in their first months of life than female newborns. Measle TR was superior to NAb TR even in case of 1st or 2nd trimester maternal SARS-CoV-2 infection. Future studies are needed to investigate possible differences in transmission of NAb following infection vs vaccination and its impact on TR.
Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired ...periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection.
MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www.clinicaltrials.gov), and gray literature sources were searched from inception to March 2023.
Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included.
All corresponding authors of the eligible studies were contacted. Cochrane’s Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy.
Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18–0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12–0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16–0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19–0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14–0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17–0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22–0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%.
A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.
Objective
The recent recrudescence of syphilis among women of childbearing age is associated with an increasing number of cases of congenital syphilis. We aimed to summarize the fetal and neonatal ...abnormalities due to congenital syphilis infection, particularly signs amenable to prenatal diagnosis.
Methods
Eligible studies were retrieved from the PubMed collection database. Articles focusing on postnatal and antenatal abnormalities covered the periods from 1969 to 2019 and 1975–2019, respectively. This review included cohort studies, case series and case reports reporting findings regarding congenital syphilis infections described before and/or after birth. Articles were reviewed by three experts in prenatal diagnosis, and all findings were classified as amenable or not amenable to prenatal diagnosis.
Results
A total of 432 cases of congenital syphilis infection were reported. Abnormalities were described antenatally in 161 cases, postnatally in 319 cases, and in both the antenatal and postnatal periods in 57 cases. The most frequently reported signs amenable to prenatal diagnosis were abdominal abnormalities (hepatomegaly, splenomegaly, and bowel abnormalities), fetal growth restriction, and elevated middle cerebral artery peak systolic velocity in the context of ascites or atypical hydrops. Brain abnormalities were rare and never isolated. In the neonatal period, the most common abnormalities were hepatosplenomegaly, bone damage and skin lesions.
Conclusion
We found that no individual sonographic sign or pattern of signs is pathognomonic for fetal syphilis. In fetuses with ultrasound abnormalities suggestive of congenital infection, syphilis must be considered as part of the work‐up.
Key points
What's already known about this topic?
Syphilis infection is markedly increasing in many countries.
Ultrasound findings in congenital syphilis remain unclear, particularly those amenable to prenatal diagnosis.
What does this study add?
The discovery of ultrasound anomalies suggestive of fetal infection, anemia, fetal hydrops, or stillbirth should be followed up with syphilis testing. Some postnatal findings can be observed in the prenatal period.
Given the recent advances in fetal medicine, there is a need for more prospective data with special attention to the effects of maternal treatment on ultrasonographic anomalies.
Congenital infection with human cytomegalovirus is a major cause of morbidity and mortality. A randomized controlled trial showed that high-dosage valacyclovir prevents cytomegalovirus disease in ...transplant recipients. Fetuses showing ultrasound features of infection are at high risk of being symptomatic at or before birth. In a pilot study, oral administration of high-dosage valacyclovir to mothers significantly decreased viral load and produced therapeutic concentrations in the blood of infected fetuses. A randomized controlled trial comparing prenatal treatment with valacyclovir against placebo in infected fetuses failed to recruit because women declined randomization. Randomized controlled trials in fetal medicine have often proven unacceptable by women who decline termination of pregnancy and are not prepared to resign themselves to the odds of the natural history of the disease.
We evaluated the efficacy of oral valacyclovir, 8 g daily, for pregnant women carrying a symptomatic cytomegalovirus-infected fetus, targeting a high-risk group for developing both neurosensory and neurological impairment.
We designed a multicenter, open-label, phase II study with 1 arm, using one of Simon’s optimal 2-stage designs. Symptomatic fetuses were defined by the presence of measurable extracerebral or mild cerebral ultrasound symptoms. They were treated in utero from prenatal diagnosis at a median of 25.9 weeks’ gestation until delivery or termination of pregnancy. Fetuses with severe brain anomalies on ultrasound were not included as were cases completely asymptomatic at presentation, because treatment was unlikely to modify either outcome. The primary endpoint was the proportion of asymptomatic neonates born to treated mothers.
At the interim analysis, 8 of 11 women delivered an asymptomatic neonate (required: ≥7). In step 2, 32 additional cases were included for a total of 43; the final number of asymptomatic neonates was 34, more than the 31 required to indicate efficacy according to the Simon 2-stage design. They remained asymptomatic at 12 months. High-dosage valacyclovir given for a median of 89 days to pregnant women carrying a moderately infected fetus was efficient at giving birth to asymptomatic neonates. Fetal blood viral loads decreased and platelet counts increased, both significantly (P = .01 and P < .001, respectively), between treatment initiation and birth after treatment completion, regardless of duration of fetal infection. Compared with a historical cohort obtained by a metaanalysis of the literature, the use of valacyclovir (8 g daily) significantly increased the proportion of asymptomatic neonates from 43% without treatment to 82% with treatment. Although the pill burden was high (16 pills a day) adherence to treatment was >90%. Finally, valacyclovir at this high dosage was extremely well tolerated.
Our results indicate that high-dosage valacyclovir given in pregnancy is effective for improving the outcome of moderately symptomatic infected fetuses. Although this study is not a randomized controlled trial, this is the first study reporting the efficacy of an antiviral drug to treat cytomegalovirus-infected fetuses. Moreover, this first study will allow new trials to be conducted, using valacyclovir as a baseline safe and effective treatment in pregnancy, to be compared to the new emerging and more potent anticytomegalovirus drugs that have not currently been tested in pregnancy.
To assess fetal and neonatal eyes abnormalities and their progression during the last ZIKV outbreak and summarize learned lessons.
A systematic review and meta-analysis was conducted by a team of ...obstetricians and ophthalmologists.
Studies reporting ocular abnormalities during the prenatal (
= 5) and postnatal (
= 24) periods were included in the analysis. In the prenatal period, the most common ocular findings were intraocular calcification cases (4/6, 66.6%) and microphthalmia (3/6, 50%). Postnatal ocular abnormalities of congenital ZIKV infection were described after birth in 479 cases. Among them microphthalmia was reported in 13 cases (13/479, 2.7%). Posterior segment (retina and optic nerve) was the most affected structure, consisting of pigmentary changes (229/479, 47.8%), macular chorioretinal atrophy (216/479, 45%), optic nerve atrophy (181/479, 37.8%), increased cup-to-disk ratio (190/479, 39.6.%), optic nerve hypoplasia (93/479,19.4%), vascular changes (26/479, 5.4%), and retinal coloboma (20/479, 4.1%). The anterior segment was involved in 4.6% (22/479) of cases, including cataract (9/479, 1.8%), lens subluxation (1/479, 0.2%), iris coloboma (5/479, 1%), and congenital glaucoma (7/479, 1.4%). These ocular anomalies were isolated in one case (1/479, 0.2%) and multiple anomalies were found in the other cases. Long-term visual disorders have been described, with no possible improvement and even a worsening of some of the ocular anomalies previously observed. No reactivation of ocular lesions was observed.
This review highlights the severe ocular abnormalities associated with congenital ZIKV infections. The importance of multidisciplinary communication between the obstetrician, the maternal-fetal medicine specialist, and the ophthalmologist is emphasized.
This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration440 188.
How I do … interpret CMV serology during pregnancy? Vauloup-Fellous, Christelle; Peyronnet, Violaine; Portet-Sulla, Vincent ...
Gynécologie, obstétrique, fertilité & sénologie,
2024-Mar-29
Journal Article
Aims
To describe the trends in anti‐infective use during pregnancy between 2010 and 2019 and determine whether they were prescribed according to drug foetal safety international classification ...systems.
Methods
We conducted a population‐based, nationwide study using the French national health data system including all pregnancies ended between 2010 and 2019. Anti‐infective agents were considered according to their pharmacological group and potential harmful risk using the Australian and Swedish classification systems. Prevalence rate was estimated annually and by trimester. Average annual percent change (AAPC) and 95% confidence intervals (CIs) were calculated using Joinpoint regression.
Results
Among 7 571 035 pregnancies, 3 027 031 (40.0%) received ≥1 antibacterial. This proportion decreased significantly from 41.5% in 2010 to 36.1% in 2019 (AAPC = −1.7%, 95%CI, −2.5 to −1.0%). Conversely, use of antiviral agents increased during the 10‐year study period for anti‐herpes simplex virus agents (AAPC = 4.4%, 3.7–5.2%), influenza agents (AAPC = 25.4%, 6.2–48.1%) and for HIV‐antiretroviral agents (AAPC = 1.3%, 0.6–2.0%). Use of influenza vaccine increased from 0.2% in 2010 to 4.2% in 2019 (AAPC = 49.7%, 39.3–60.9%). Among all pregnancies, 0.9% had been exposed to a potentially harmful anti‐infective agent increasing from 0.7% in 2010 to 1.2% in 2019 (AAPC = 6.4%, 4.4–8.5%).
Conclusion
Based on >7 million pregnancies identified from French nationwide data, this study showed that antibacterials are frequently prescribed during pregnancy although their use has decreased over the past 10 years. Our results suggest that anti‐infective agents are generally prescribed in accordance with recommendations, although with a potential for improvement in influenza vaccination.
BackgroundTreatment of COVID-19 is mostly symptomatic, but a wide range of medications are under investigation against SARS-CoV-2. Although pregnant women are excluded from clinical trials, they will ...inevitably receive therapies whenever they appear effective in non-pregnant patients and even under compassionate use.MethodWe conducted a review of the literature on placental transfer and pregnancy safety data of drugs under current investigation for COVID-19.ResultsRegarding remdesivir, there are no data in pregnant women. Several other candidates already have safety data in pregnant women, since they are repurposed drugs already used for their established indications. They may thus be used in pregnancy, although their safety in the context of COVID-19 may differ from conventional use. These include the HIV protease inhibitors such as lopinavir/ritonavir which have low placental transfer; interferon which does not cross the placental barrier, and (hydroxy) chloroquine, which have high placental transfer. There are also pregnancy safety and placental transfer data for colchicine, steroids, oseltamivir and azithromycin, as well as some monoclonals. However, some drugs are strictly prohibited in pregnancy due to known teratogenicity (thalidomide) or fetal toxicities (renin-angiotensin system blockers). Other candidates including tocilizumab and other IL-6 inhibitors, umifenovir and favipiravir have insufficient data on pregnancy outcomes.ConclusionIn life-threatening cases of COVID-19, the potential risks of therapy to the fetus may be more than offset by the benefit of curing the mother. While preclinical and placental transfer studies are required for a number of potential anti-SARS CoV2 drugs, several medications can already be used in pregnant women.
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