Prevalência de nascimentos prematuros como desfechos de infecções pela COVID-19 na gestação / Prevalence of Preterm Birth as an Outcome of COVID-19 Infections during Pregnancy / Prevalencia de nacimientos prematuros producto de la infección por COVID-19 durante el embarazo

Objetivo: estimar a prevalência de nascimento prematuro em gestantes infectadas pela Covid-19, comparar índices de prematuridade entre infectadas e não infectadas e elucidar fatores associados à prematuridade. Métodos: coorte retrospectiva, com coleta de dados por inquérito online, de abril a dezembro de 2022, com mulheres que estiveram gestantes durante a pandemia, com acesso à internet, idade superior a 18 anos e que preencheram o primeiro inquérito online. Protocolo de pesquisa aprovado pelo Comitê de Ética. Resultados: primeiro inquérito respondido por 304 gestantes/puérperas, e o segundo por 82 (27%), compondo a amostra final. O índice de prematuridade no primeiro inquérito foi de 7,2% (n=14), já no segundo, 8,5% (n=7). A infecção pela Covid-19 não foi associada à prematuridade. A prematuridade associou-se a baixo peso, à necessidade de internação em centros de terapia intensiva neonatal e internações após o nascimento. Conclusão: a infecção pela Covid-19 não influenciou no aumento de nascimentos prematuros.

Objective: to estimate the prevalence of preterm birth in pregnant women infected with Covid-19, compare prematurity rates between infected and non-infected, and elucidate factors associated with prematurity. Methods: a retrospective cohort study was conducted using online survey data collected from April to December 2022, involving women who were pregnant during the pandemic, had internet access, were over 18 years old, and completed the initial online survey. The research protocol was approved by the Ethics Committee. Results: the initial survey was completed by 304 pregnant/postpartum women, and the follow-up survey by 82 (27%), comprising the final sample. The preterm birth rate in the initial survey was 7.2% (n=14), and in the follow-up survey, it was 8.5% (n=7). Covid-19 infection was not associated with prematurity. Prematurity was associated with low birth weight, the need for neonatal intensive care unit admission, and postnatal hospitalizations. Conclusion: Covid-19 infection did not influence an increase in preterm births.

Objetivo: estimar la prevalencia de partos prematuros en gestantes infectadas por Covid-19, comparar las tasas de prematuridad entre gestantes infectadas y no infectadas y determinar los factores asociados a la prematuridad. Métodos: estudio de cohorte retrospectivo, con recolección de datos mediante encuesta online, de abril a diciembre de 2022, con mujeres que estuvieron embarazadas durante la pandemia, con acceso a internet, mayores de 18 años y que completaron la primera encuesta online. El protocolo de investigación fue aprobado por el Comité de Ética. Resultados: la primera encuesta fue respondida por 304 gestantes/puérperas, y la segunda por 82 (27%), que conformaron la muestra final. La tasa de prematuridad en la primera encuesta fue del 7,2% (n=14), en la segunda, del 8,5% (n=7). La infección por Covid-19 no se asoció con la prematuridad. La prematuridad se asoció con bajo peso, necesidad de internación en centros de cuidados intensivos neonatales e internaciones después del nacimiento. Conclusión: La infección por Covid-19 no influyó en el aumento de nacimientos prematuros.

Gestational urinary concentrations of glyphosate and aminomethylphosphonic acid in relation to preterm birth: the MIREC study.

BACKGROUND: Few high-quality studies have evaluated associations between urinary glyphosate or its environmental degradate (aminomethylphosphonic acid (AMPA)] and preterm birth (PTB). OBJECTIVES: To quantify associations between urinary glyphosate and AMPA and preterm birth in the pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study and determine if associations differ by fetal sex. METHODS: We measured first trimester urinary glyphosate and AMPA concentrations in MIREC participants who were recruited between 2008-2011 from 10 Canadian cities. Of the 1880 participants whose first trimester urine samples were analyzed for glyphosate or AMPA, 1765 delivered a singleton, live birth. Our primary outcome was preterm birth (PTB) defined as births occurring between 20 and <37 weeks. Secondary outcomes were spontaneous preterm births (sPTB) and gestational age. We modelled the hazard of PTB and sPTB using discrete time survival analysis with multivariable logistic regression to calculate odds ratios (OR). We used multivariable linear regression models to quantify associations between analytes and gestational age. To assess effect modification by fetal sex, we stratified all models and calculated interaction terms. In the logistic regressions models we additionally calculated the relative excess risk due to interaction. RESULTS: Six percent (n = 106) of the study population delivered preterm, and 4.7% (n = 83) had a spontaneous preterm birth. Median specific-gravity standardized concentrations of glyphosate and AMPA were 0.25 and 0.21 µg/L. Associations between both glyphosate or AMPA and PTB, sPTB, and gestational age centered around the null value. The adjusted ORs of PTB for each doubling of glyphosate and AMPA concentrations were 0.98 (95% CI: 0.94, 1.03) and 0.99 (95% CI: 0.92, 1.06) respectively. We observed no evidence of differences by fetal sex. CONCLUSIONS: In this Canadian pregnancy cohort, neither glyphosate nor AMPA urinary concentrations was associated with PTB or reduced gestational length.

Synbiotics in patients at risk for spontaneous preterm birth: protocol for a multi-centre, double-blind, randomised placebo-controlled trial (PRIORI).

BACKGROUND: Prematurity remains one of the main causes of neonatal morbidity and mortality. Approximately two thirds of preterm births are spontaneous, i.e. secondary to preterm labour, preterm prelabour rupture of membranes (PPROM) or cervical insufficiency. Etiologically, the vaginal microbiome plays an important role in spontaneous preterm birth (sPTB). Vaginal dysbiosis and bacterial vaginosis are well-known risk factors for ascending lower genital tract infections and sPTB, while a Lactobacillus crispatus-dominated vaginal microbiome is associated with term deliveries. Synbiotics may help to achieve and/or maintain a normal, Lactobacillus-dominated vaginal microbiome. METHODS: We will perform a multi-centre, double-blind, randomised, placebo-controlled trial. Women aged 18 years or older with a singleton pregnancy are eligible for inclusion at 80/7-106/7 weeks gestational age if they have one or more of the following risk factors for sPTB: previous sPTB at 240/7-356/7 weeks, prior PPROM before 360/7 weeks, or spontaneous pregnancy loss at 140/7-236/7 weeks of gestation. Exclusion criteria are multiple gestation, cervix conisation, inflammatory bowel disease, uterine anomaly, and the use of pro-/pre-/synbiotics. Patients will be randomised to oral synbiotics or placebo, starting before 11 weeks of gestation until delivery. The oral synbiotic consists of eight Lactobacillus species (including L. crispatus) and prebiotics. The primary outcome is the gestational age at delivery. Vaginal microbiome analysis once per trimester (at approximately 9, 20, and 30 weeks) and delivery will be performed using metataxonomic sequencing (16S rRNA gene) and microbial culture. Secondary outcomes include PPROM, the use of antibiotics, antenatal admission information, and neonatal outcomes. DISCUSSION: This study will evaluate the effect of oral synbiotics on the vaginal microbiome during pregnancy in a high-risk population and correlate the microbial changes with the gestational age at delivery and relevant pregnancy outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05966649. Registered on April 5, 2024.

Socioeconomic and ethnic disparities in preterm births in an English maternity setting: a population-based study of 1.3 million births.

BACKGROUND: Preterm birth is a major cause of infant mortality and morbidity and accounts for 7-8% of births in the UK. It is more common in women from socially deprived areas and from minority ethnic groups, but the reasons for this disparity are poorly understood. To inform interventions to improve child survival and their quality of life, this study examined the socioeconomic and ethnic inequalities in preterm births (< 37 weeks of gestation at birth) within Health Trusts in England. METHODS: This study investigated socioeconomic and ethnic inequalities in preterm birth rates across the National Health Service (NHS) in England. The NHS in England can be split into different units known as Trusts. We visualised between-Trust differences in preterm birth rates. Health Trusts were classified into five groups based on their standard deviation (SD) variation from the average national preterm birth rate. We used modified Poisson regression to compute risk ratios (RR) and 95% confidence intervals (95% CI) with generalised estimating equations. RESULTS: The preterm birth rate ranged from 6.8/100 births for women living in the least deprived areas to 8.8/100 births for those living in the most deprived areas. Similarly, the preterm birth rate ranged from 7.8/100 births for white women, up to 8.6/100 births for black women. Some Health Trusts had lower than average preterm birth rates in white women whilst concurrently having higher than average preterm birth rates in black and Asian women. The risk of preterm birth was higher for women living in the most deprived areas and ethnicity (Asian). CONCLUSIONS: There was evidence of variation in rates of preterm birth by ethnic group, with some Trusts reporting below average rates in white ethnic groups whilst concurrently reporting well above average rates for women from Asian or black ethnic groups. The risk of preterm birth varied substantially at the intersectionality of maternal ethnicity and the level of socioeconomic deprivation of their residency. In the absence of other explanations, these findings suggest that even within the same Health Trust, maternity care may vary depending on the women's ethnicity and/or whether she lives in an area of high socioeconomic deprivation. Thus, social factors are likely key determinants of inequality in preterm birth rather than provision of maternity care alone.

Comparative effectiveness of treating prenatal depression with counseling versus antidepressants in relation to preterm delivery.

BACKGROUND: Maternal depression during pregnancy is prevalent and has been associated with increased risk of preterm delivery. However, comparative effectiveness of 2 commonly used treatment options, mental health counseling and use of antidepressants, in mitigating the risk of preterm delivery associated with maternal depression remains uncertain. Although antidepressant use has been associated with increased risk of preterm delivery in many previous studies, a direct head-to-head comparison between these 2 treatment options has not been investigated. Thus, the comparative risk-benefit profiles of those 2 treatment options remain unclear. OBJECTIVE: To determine the comparative effectiveness of 2 commonly used options for treating prenatal depression in limiting the risk of preterm delivery associated with maternal depression. STUDY DESIGN: A large prospective cohort study was conducted among 82,170 pregnant women at Kaiser Permanente Northern California, an integrated health care delivery system. Clinically diagnosed depression and its treatments (use of antidepressants and mental health counseling) were identified from the Kaiser Permanente Northern California electronic health record system. Gestational age was also recorded for all deliveries and captured by electronic health records for determining preterm delivery. RESULTS: Using Cox proportional hazards regression incorporating propensity score methodology to ensure comparability between comparison cohorts, relative to those without depression, pregnant women with untreated depression had 41% increased risk of preterm delivery: adjusted hazard ratio=1.41, 95% confidence interval=1.24 to 1.60, confirming increased risk of preterm delivery associated underlying maternal depression. Relative to untreated depression, any mental health counseling was associated with an 18% of reduced risk of preterm delivery: adjusted hazard ratio=0.82 (0.71-0.96). The inverse association showed a dose-response pattern: increased number of counseling visits was associated with greater reduction in preterm delivery risk with 43% reduction in preterm delivery risk associated with 4 or more visits (adjusted hazard ratio=0.57, 95% confidence interval=0.45-0.73). In contrast, use of antidepressants during pregnancy was associated with an additional 31% increased risk of preterm delivery independent of underlying depression: adjusted hazard ratio=1.31, 95% confidence interval=1.06 to 1.61. This positive association also showed a dose-response relationship: a longer duration of use was associated with an even higher risk. CONCLUSION: This study provides much needed evidence regarding the comparative effectiveness of 2 common treatment options for prenatal depression in the context of preterm delivery risk. The results indicate that, to reduce preterm delivery risk due to maternal depression, mental health counseling is more effective. Use of antidepressants may add additional risk of preterm delivery, independent of the underlying depression. The findings provide data for clinicians and pregnant women to make informed and evidence-based treatment decisions that take into account the risks and benefits to both maternal and fetal health.

Cooperation of aquaporin 5 and the adrenergic system in the initiation of birth in rat model.

Aquaporins (AQPs) are involved in the process of implantation, regulate myometrial contractions and cervical ripening, and maintain appropriate placental functioning. The molecular mechanism of these functions is not fully understood. Our study aimed to investigate the physiological significance of AQP5 during pregnancy and to determine the cooperation between the adrenergic system and the AQP5 in uterine contraction in the late-pregnant rat uterus. After administering AQP5 siRNA intraperitoneally to Sprague-Dawley rats, the length of the gestational period was determined and the changes in uterine contractions were measured in an isolated organ bath system. Pharmacological influence on AQP5 expression and uterine contraction was investigated by treatment with terbutaline (10 mg/kg, subcutaneously) and doxazosin (5 mg/kg, orally) in vivo; and mercuric chloride (HgCl2), in vitro. Moreover, the levels of cAMP response element binding protein (CREB) were measured in the uterus by an ELISA kit. The gestational period became shorter, AQP5 expression significantly decreased and rat uterus contraction increased after AQP5 siRNA treatment compared to the control. Treatment with terbutaline significantly increased AQP5 mRNA and protein expression after 30 min and continuously reduced it until 90 min, whereas doxazosin treatment did not significantly alter AQP5 expression. Treatment with the AQP5 antagonist HgCl2 increased spontaneous uterus contraction and decreased norepinephrine-induced uterus contraction with decreasing AQP5 expression in pregnant rat uterus. Moreover, the tocolytic effect through the adrenergic system was amplified in the presence of an AQP5 antagonist, presumably via the changes in cAMP level. In conclusion, our findings elucidate the collaborative role of aquaporin 5 (AQP5) and adrenergic systems in the regulation of uterine contractions in late-pregnant rats. Our findings suggest this may be a good starting point for developing a new tocolytic therapy.

Effect of access to antenatal care on risk of preterm birth among migrant women in Italy: A population-based cohort study.

Objective: To evaluate the association between maternal migration status and preterm birth, and whether a better adherence to antenatal care during pregnancy mitigates the risk of preterm birth. Design: Population-based cohort. Setting: Administrative databases of the Lombardy region, Italy. Population: First singleton births of women aged 15-55 years at 22-42 gestational weeks, between 2016 and 2021. Methods: Assessed the risk of preterm birth (<37 weeks). Main outcome measures: A multivariable logistic regression mediation model calculated the mediation effect of adherence to antenatal care in the association between maternal migrant status and preterm birth and the residual effect not mediated by it. Analyses were adjusted for the socio-demographic and pregnant characteristics of the women. Results: Of 349,753 births in the cohort, Italian nationality accounted for 71 %; 28.4 % were documented migrants and 0.4 % undocumented migrants. Among them, 5.3 %, 6.4 %, and 9.3 % had a preterm birth, respectively. Using deliveries of Italian citizens as referent, migrants had a significantly increased risk of preterm birth (adjusted relative risk: 1.22, 95 % confidence interval: 1.18-1.27). Adherence to antenatal care mediated the 62 % of such risk. We have calculated that adherence to antenatal pathways set to the highest level for the whole population could lead to a 37 % reduction in preterm birth risk. Conclusion: Part of the excess of preterm birth among documented and undocumented migrants in Italy can be explained by a lack of adherence to the antenatal care path despite equal access to National Health care. The adherence of all pregnant women to antenatal care would reduce the risk of preterm birth by about one-third.

Maternal and fetal risk factors for congenital anomalies of the kidney and urinary tract: a birth cohort study in urban China.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common causes of kidney diseases in children. Previous studies on CAKUT etiologies have been predominantly focused on non-modifiable genetic risk factors. The existing nongenetic studies are limited by lack of comprehensive investigation of potentially modifiable risk factors and the inability to distinguish among various phenotypes of CAKUT. Therefore, this study aimed to comprehensively evaluate both maternal and fetal risk factors of CAKUT, sorted by disease phenotype. METHODS: A prospective birth cohort study was conducted among 10,179 women who delivered a singleton live newborn in Lanzhou, China, between 2010 and 2012. Face-to-face interviews were conducted among the participants within 1-3 days after delivery using standard questionnaires to collect information on maternal demographics and characteristics. All newborns underwent postnatal renal ultrasonographic screening during their routine 1-month checkup. Clinical data, including birth outcomes and maternal complications, were confirmed by reviewing their medical records. Maternal and fetal risk factors were compared in children with and without CAKUT. Multivariable logistic regression analysis was performed to identify independent risk factors of CAKUT and their phenotypes, respectively. RESULTS: A total of 489 (4.8%) cases of CAKUT were identified. Logistic regression revealed that maternal overweight (pre-pregnancy), gestational diabetes, preterm birth, and low birth weight were independent risk factors for CAKUT. Maternal overweight increased the risk of vesicoureteral reflux (VUR, odds ratio (OR) = 1.441, 95% confidence interval (CI) 1.010-2.057) and posterior urethral valves (PUV, OR = 1.868, 95% CI 1.074-3.249). Gestational diabetes increased the risk of ureteropelvic junction obstruction (UPJO, OR = 1.269; 95% CI 1.044-1.543) and posterior urethral valves (OR = 1.794; 95% CI 1.302-2.474). Preterm birth increased the risk of ureteropelvic junction obstruction (OR = 1.056; 95% CI 1.004-1.111). CONCLUSIONS: Our study identified various risk factors associated with different CAKUT phenotypes, stressing the importance of separate analyses for each phenotype. Our findings may provide helpful guidance on developing targeted and effective CAKUT prevention programs in the future.

Genetic association study of preterm birth and gestational age in a population-based case-control study in Peru.

BACKGROUND: Preterm birth (PTB) affects ∼15 million pregnancies worldwide. Genetic studies have identified several candidate loci for PTB, but results remain inconclusive and limited to European populations. Thus, we conducted a genome-wide association study (GWAS) of PTB and gestational age at delivery (GA) among 2,212 Peruvian women. METHODS: PTB cases delivered≥20 weeks' but < 37 weeks' gestation, while controls delivered at term (≥37 weeks but <42 weeks). Multivariable regressions were used to identify genetic markers for PTB and GA (∼6 million SNPs), adjusting for maternal age and the first two genetic principal components. In silico functional analysis was conducted among top signals detected with an arbitrary P < 1.0×10-5 . We sought to replicate genetic markers for PTB and GA identified in Europeans, and we developed a genetic risk score for GA based on European markers. RESULTS: Mean GA was 30 ± 4 weeks in PTB cases (N = 933) and 39 ± 1 in the controls (N = 1,279). No associatiosn were identified at genome-wide level. Nominal PTB variants were enriched for biological pathways associated with polyketide, progesterone, steroid hormones, and glycosyl metabolism. Nominal GA variants were enriched in intronic regions and cancer pathways. Variants in WNT4 associated with GA in Europeans were replicated in our study. A genetic risk score was associated with a 2-day longer GA (P = 0.002) in our sample. CONCLUSIONS: This study identified various signals suggestively associated with PTB and GA in pregnant Peruvian women. None of these variants overlapped with signals previously identified in Europeans.

Vaginal microbiota of pregnant women with Ureaplasma urealyticum and Mycoplasma hominis infections.

Background: The association between preterm birth and Mycoplasma species such as Mycoplasma hominis and Ureaplasma urealyticum has been extensively investigated. In a clinical setting, conventional diagnostic methods for them involve culture methods for Mycoplasma spp. and Ureaplasma spp., along with PCR tests. However, the clinical utility of these tests remains controversial, highlighting the necessity for more robust and reliable methods for identifying and understanding Mycoplasma infections. Objective: This study aimed to assess the distribution of microbiota in pregnant women with Mycoplasma hominis and Ureaplasma urealyticum infection by the comparison of conventional diagnostic methods with vaginal microbial community analysis. Study Design: This prospective case-control study involved 228 Korean pregnant women and utilized vaginal microbial community analysis, Ureaplasma/Mycoplasma culture, and 12-multiplex PCR for sexually transmitted diseases. Cross-correlation analysis in SPSS 27 compared the results of two conventional methods with vaginal microbial community analysis. R software generated box plots depicting the relative abundance of microorganisms. Network analysis was conducted using Cytoscape. Results: Positive Ureaplasma urealyticum culture findings were observed in 60.2% of patients, with 76.4% positive for Ureaplasma parvum PCR and 13.2% positive for Ureaplasma urealyticum PCR. Mycoplasma hominis culture was positive only in two patients, while Mycoplasma hominis PCR was positive in eight women. Vaginal microbial community analysis identified significant differences in relative abundances of Gardnerella species type I and Fannyhessea vaginae between the Ureaplasma urealyticum PCR positive and negative groups. Mycoplasma hominis PCR positive patients exhibited significant differences in 11 bacterial species, including Gardnerella species I and Fannyhessea vaginae. Conclusion: This study suggests that STD-PCR may be more accurate than Ureaplasma/Mycoplasma culture for the diagnosis of Mycoplasma hominis and Ureaplasma urealyticum infection. Also, the presence of Gardnerella species I and Fannyhessea vaginae implies their potential influences on Ureaplasma urealyticum and Mycoplasma hominis infections based on results of vaginal microbial community analysis. Therefore, vaginal microbial community analysis may give the more information of their pathophysiology.

The intergenerational metabolic-cardiovascular life course: maternal body mass index (BMI), offspring BMI, and blood pressure of adolescents born extremely preterm.

BACKGROUND: The aim of this study was to evaluate associations between pre-pregnancy maternal obesity and adolescent blood pressures (BPs) among children born extremely preterm. METHODS: This longitudinal observational cohort study included participants in the multicenter Extremely Low Gestational Age Newborn (ELGAN) study, born before 28 weeks of gestation, recruited at birth between 2002 and 2004, and followed prospectively through late adolescence. Between 2015 and 2022, three oscillometric BPs were obtained from participants (mean age 17.8 years). We used linear regression modeling to evaluate the association between maternal self-reported pre-pregnancy body mass index (BMI) and offspring adolescent systolic BP (SBP). In secondary analyses, we evaluated the association between maternal pre-pregnancy and offspring preadolescent (10-year-old) BMI and between offspring preadolescent BMI and adolescent SBP. RESULTS: The 100 (24%) participants born to a mother with a history of pre-pregnancy obesity (BMI ≥ 30) had a greater mean SBP of 120.5 (± 14.3) mmHg compared to the 324 (76%) of adolescents born to mothers without pre-pregnancy obesity (SBP 115.6 (± 12.0) mmHg). Pre-pregnancy obesity was associated with higher offspring BMI (aß 10.8, 95% CI 2.3, 19.2), and higher offspring BMI was associated with higher adolescent SBP (aß 0.12, 95% CI 0.09,0.16). CONCLUSIONS: For ELGANs, higher maternal pre-pregnancy BMI was associated with higher adolescent SBP. Findings from secondary analyses suggest potential mediation through preadolescent BMI. Future research directions include multi-level interventions to reduce maternal pre-pregnancy obesity, followed by offspring obesity prevention interventions as a way of reducing intergenerational cardiovascular disease in high-risk infants born extremely preterm.

Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan.

BACKGROUND: Antenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan. METHODS: This retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1-7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge. RESULTS: The ACS 1-7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1-7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group. CONCLUSIONS: An ACS-to-delivery interval of 1-7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further.

Placental Mosaicism for Autosomal Trisomies: Comprehensive Follow-up of 528 Danish Cases (1983-2021): Placental mosaicism for autosomal trisomies.

BACKGROUND: Mosaicism, characterized by the presence of two or more chromosomally distinct cell lines, is detected in 2-4% of chorionic villus samples. In these cases, the aberration may be confined to the placenta or additionally present in the fetus. Fetal involvement may manifest as fetal malformations, while confined placental mosaicism poses risks such as preterm birth and low birth weight. Differentiating between true fetal mosaicism and confined placental mosaicism at the time of the chorionic villus sampling is challenging and requires follow-up by an amniocentesis and ultrasonography. OBJECTIVES: To estimate the risk of fetal involvement or adverse pregnancy outcomes for specific chromosomes after detecting mosaicism for an autosomal trisomy in a chorionic villus sample and identify high (red), intermediate (yellow) and low (green) risk chromosomes. Further, to explore possible associations with level of mosaicism and screening parameters. STUDY DESIGN: A retrospective descriptive study of all singleton pregnancies with mosaicism detected in chorionic villus samples from 1983-2021 identified in the Danish Cytogenetic Central Registry and the Danish Fetal Medicine Database. RESULTS: Of 90,973 chorionic villus samples, 528 cases had mosaicism involving an autosomal trisomy and where genetic follow-up had been performed. The overall risk of fetal involvement was 13% (69/528) with extensive variations depending on which chromosome was involved (e.g., trisomy 7: 0% (0/55) or trisomy 21: 46% (19/41)). Higher levels of mosaicism in the chorionic villus sample suggested fetal involvement as mean mosaic level was 55% in true fetal mosaics vs 28% in cases confined to the placenta (p=0.0002). In cases with confined placental mosaicism (459/528), the risk of delivering small-for-gestational-age neonates was 14% (48/341). The risk of preterm birth (before 37 weeks) was 15% (51/343). The collective risk of adverse outcome was 22% (76/343) in pregnancies that continued and where information on birth weight and gestational age at birth was available. Adverse outcomes varied substantially between chromosomes. Also, multiple-of-the-median (MoM) values of pregnancy-associated plasma protein A was predictive of these issues as it was significantly lower in cases with adverse outcome compared to cases with a normal outcome (small for gestational age: 0.23 MoM vs 0.47 MoM, p<0.0001) or preterm birth: 0.25 MoM vs 0.47 MoM, p<0.0001). After the introduction of combined first trimester screening in 2004, the detection of cases with fetal involvement seemed to increase as the risk before 2004 was 9% (16/174) compared to 15% (53/354) after 2004 (risk ratio: 1.7 (95% CI: 1.0;2.8)). The risk of adverse outcome in confined placental mosaicism pregnancies increased from 16% (22/139) before 2004 to 27% (55/204) after 2004 (risk ratio 1.7 (95% CI: 1.1;2.7)) CONCLUSIONS: Introducing combined first trimester screening increased the detection of placental mosaicism with fetal involvement and confined placental mosaicism with adverse outcome. In cases of mosaicism in chorionic villus samples, the risk of fetal involvement and adverse outcomes varied considerably between chromosomes. Importantly, adverse outcomes were seen in confined placental mosaicism for many trisomies besides trisomy 16.

Association between gestational hypnotic benzodiazepine receptor agonists exposure and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: Hypnotic benzodiazepine receptor agonists (HBRA) are frequently prescribed in pregnancy but little is known about their effects on pregnancy outcomes. Herein, we systematically reviewed the evidence on the effects of HBRA exposure during pregnancy and risk of preterm birth (PTB), small for gestational age (SGA), birth defects, and low birth weight (LBW). METHODS: We reviewed the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science from the earliest possible date to 17th May 2024 and included all studies examining adverse pregnancy outcomes with gestational exposure to HBRA. RESULTS: Nine studies were included. Meta-analysis showed that HBRA exposure led to a significant increase in the risk of PTB (OR: 1.28 95% CI: 1.05, 1.56 I2 = 73%), SGA (OR: 1.24 95% CI: 1.18, 1.30 I2 = 0%), and LBW (OR: 1.51 95% CI: 1.27, 1.78 I2 = 26%). We noted no significant association between HBRA exposure in pregnancy and subsequent birth defects (OR: 0.90 95% CI: 0.63, 1.28 I2 = 56%). Subgroup analysis based on exposure time, type of HBRA, method of assessment of exposure, control of psychiatric diagnosis, and psychotropic drugs altered the results of PTB and SGA but not for birth defects. CONCLUSION: HBRA exposure during pregnancy may lead to a small but significant increase in the risk of PTB, SGA, and LBW. HBRA is not associated with an increased risk of birth defects. There are several limitations of current evidence especially with regards to adjustment for psychiatric illness and co-mediations which need to be overcome by future studies.

Job strain and adverse pregnancy outcomes: A scoping review and meta-analysis.

BACKGROUND: Previous studies have shown that job strain is associated with low birthweight (LBW), preterm birth (PTB), and small for gestational age (SGA). We conducted a scoping review and meta-analysis to assess the association between job strain and adverse pregnancy outcomes. METHODS: A literature search was performed on PubMed. We included English-language studies that examined the association between job strain (based on the Karasek demand-control model) and pregnancy outcomes. We excluded letters, posters, reviews, and qualitative studies. Random effects meta-analysis was performed. Heterogeneity was assessed using τ2 and I2 statistics. Potential bias was assessed using standard funnel plots. Asymmetry was evaluated by Egger's test. Leave-one-out analysis was performed for sensitivity analyses. RESULTS: Three eligible studies were found for LBW, seven for PTB, and four for SGA. The number of subjects ranged from 135 to 4889, and the prevalence of high job strain ranged from 6.64% to 33.9%. The pooled odds ratio and 95% confidence interval (CI) for LBW, PTB, and SGA were 1.23 (95% CI: 0.97, 1.56), 1.10 (95% CI: 1.00, 1.22), and 1.16 (95% CI: 0.97, 1.39) respectively, indicating modest associations. Heterogeneity for LBW and PTB may not be important but may be moderate for SGA. No publication bias was detected for LBW and PTB, but possible publication bias exists for SGA. CONCLUSION: We found a modest association between job strain and PTB. Since job strain is only one of the many aspects of an unhealthy work environment, interventions that improve working conditions more broadly are needed.

Utilizing Modified Coopland's Scoring System to Identify and Predict the Outcome of High-Risk Pregnancies in Resource-Limited Settings: A Retrospective Review.

Introduction A high-risk pregnancy is associated with adverse maternal and foetal outcomes. Women with high-risk pregnancies are at a greater risk of developing antepartum haemorrhage, miscarriages, and the need for surgical interventions. Neonatal complications include preterm births, low birth weight (LBW), intra-uterine deaths and an increased need for NICU admission. The utilisation of low-cost scoring tools for identifying high-risk women can aid in early diagnosis and timely implementation of therapeutic interventions.  Objective The retrospective record-based study sought to calculate the proportion of high-risk pregnancies using modified Coopland's scoring system and compare the maternal and foetal outcomes among high-risk pregnancies. Methods The study retrospectively analysed the records of antenatal women in their third trimester from the years December 2018 to December 2021. Each record was then numerically assessed according to the modified Coopland's scoring system and categorised according to the risk status. Maternal and neonatal outcomes were then compared across the risk groups. Results The data included 300 cases over a three-year period. According to modified Coopland's scoring system, we found that the overall proportion of high-risk pregnancies was 18.3%. Adverse maternal and fetal outcomes were increased in high-risk pregnancy groups when compared to low-risk pregnancies, miscarriages (31.6% vs 15.8%) and antepartum haemorrhage (55.6% vs 11.1%). Babies born to high-risk mothers had a higher chance of developing LBW status (52.0%) and respiratory distress (45.5%) when compared to those born to low-risk mothers: 8.0% and 13.6%, respectively. Conclusion A notable portion of pregnant women were classified as high-risk using modified Coopland's scoring tool and would benefit from targeted obstetric care.

The effects of proton pump inhibitors during pregnancy on treatment of preeclampsia, and related outcomes: a systematic review and meta-analysis.

OBJECTIVE: This systematic review evaluated the available evidence of the effects of PPIs during pregnancy on preeclampsia and related maternal, fetal and neonatal outcomes. DATA SOURCES: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, and Global Medicus Index) were searched on 17 November 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials involving pregnant women, using any class or dose of PPIs, were eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analysis was conducted for all outcomes of interest, with random-effects models. Results were presented as risk ratios or mean difference. Quality assessment was performed using the Risk of Bias 2 tool, and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessment was completed to evaluate the certainty of the evidence. The study was registered on PROSPERO (CRD42023423673). RESULTS: Our search identified 3,879 records, which were screened by two authors independently. Nine reports (describing eight trials) met our eligibility criteria, however six trials were ultimately excluded from our analysis as women were only given PPIs immediately prior to Cesarean section for acid aspiration prevention. The two trials included in the meta-analysis evaluated the treatment of 177 women with diagnosed preeclampsia. For the primary outcomes, moderate-certainty evidence showed there is likely no effect of the use of PPIs on risk of HELLP syndrome (RR 1.21, 95% CI 0.37 - 3.99, I²â€¯= 0%) or perinatal mortality (RR 0.81, 95% CI 0.36 - 1.79, I²â€¯= 0%), while there were insufficient data to meta-analyse all other primary outcomes, including eclampsia and neonatal mortality. No trials investigated PPIs for preventing preeclampsia. CONCLUSIONS: Given the limited outcome data we are uncertain of the effect of PPIs in women with preeclampsia. Further trials are required to determine what (if any) effects PPIs might have for preeclampsia prevention or treatment.

Moderating Effect of General Self-Efficacy on the Relationship between Pregnancy Stress, Daily Hassles Stress, and Preterm Birth Risk in Women Experiencing Preterm Labor: A Cross-Sectional Study.

PURPOSE: This study investigated the moderating role of general self-efficacy (GSE) on how stress caused by pregnancy and daily hassle affect the risk of preterm birth (PTB) in women experiencing preterm labor. METHODS: This cross-sectional study included 196 pregnant women experiencing preterm labor before 37 weeks of gestation. We used IBM SPSS Statistics 27 and employed Hayes process macro version 4 (model 1) and hierarchical regression to analyze the moderating effect of GSE on the relationship between pregnancy stress, daily hassle stress, and PTB risk. RESULTS: Stress caused by pregnancy and daily hassle was positively correlated to PTB risk (r = .54, p < .001; r = .25, p < .001, respectively). While GSE did not significantly correlate with pregnancy stress, it negatively correlated with daily hassle stress (r = - .19, p = .009). GSE significantly moderated the relationship between combined stressors and PTB risk. As GSE levels increased, escalation in PTB risk in response to increasing stress levels was a more pronounced, highlighting a complex interaction between higher GSE levels and response to escalating stress levels. This model accounted for 39.5% of the variance in the PTB risk. CONCLUSION: Higher GSE may amplify the impact of stress on PTB risk, rather than mitigate it, which suggests a more nuanced role of GSE in the stress response of pregnant women at risk of preterm labor. GSE should be considered in care strategies, and managing its impact on stress perception and responses in pregnant women is crucial.

The influence of antenatal betamethasone timing on neonatal outcome in late preterm infants: a single-center cohort study.

PURPOSE: Many pregnancies continue after antenatal corticosteroid exposure. Since long-term effects on late preterm neonatal outcome remain controversial, it remains unknown whether pregnant women who are at risk for preterm birth during the late preterm period and had prior antenatal corticosteroid exposure would benefit from an additional course of antenatal corticosteroids. We evaluated the need for future trials on this topic by comparing short term effects from antenatal betamethasone to long-term effects. We also examined the value of a risk-adapted approach. METHODS: We observed neonatal outcomes in late preterm infants (34/0-36/0 weeks of gestation) who were exposed to antenatal betamethasone either up to 10 days prior birth (n = 8) or earlier in pregnancy (n = 89). We examined a real world population from the University Hospital Magdeburg (Germany) between 01 January 2012 and 31 December 2018, and a simulated high-risk population that was derived from the original data. RESULTS: The indicators for relevant adverse outcomes did not differ in the unselected population. In the simulated high-risk population, recent antenatal corticosteroid administration significantly reduced the incidence of relevant cardiorespiratory morbidities (OR = 0.00, p = 0.008), and reduced the number needed to treat from 3.7 to 1.5. CONCLUSION: The superiority of recent antenatal corticosteroid administration in the late preterm period over earlier exposure strongly depended on the prevalence of respiratory disease. Before considering clinical trials on additional antenatal corticosteroid courses in the late preterm period, antenatal assessment tools to predict respiratory morbidity need to be developed.

Pregnancies with 'double-positive' multiple marker screening results: a population-based study in Ontario, Canada.

BACKGROUND: Multiple marker screening is offered to pregnant individuals in many jurisdictions to screen for trisomies 21 and 18. On occasion, the result is 'double-positive'-a screening result that is unexpectedly positive for both aneuploidies. Although this occurs rarely, the paucity of available evidence about the outcomes of these pregnancies hinders patient counselling. This study aimed to investigate the association of double-positive results with preterm birth and other adverse perinatal outcomes. METHODS: We conducted a population-based retrospective cohort study of pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, using province-wide perinatal registry data in Ontario, Canada. Pregnancies with double-positive screening results where trisomies 21 and 18 were ruled-out were compared to pregnancies with screen negative results for both aneuploidies. We used modified Poisson regression models with robust variance estimation to examine the association of double positive results with preterm birth and secondary outcomes. RESULTS: From 429 540 pregnancies with multiple marker screening, 863 (0.2%) had a double-positive result; trisomies 21 and 18 were ruled out in 374 pregnancies, 203 of which resulted in a live birth. Among the pregnancies in the double-positive group resulting in a live birth, the risk of preterm birth was increased compared to pregnancies with a screen negative result: adjusted risk ratio (aRR) 2.6 (95%CI 2.0-3.6), adjusted risk difference (aRD) 10.5% (95%CI 5.4-15.7). In a sensitivity analysis excluding all diagnosed chromosomal abnormalities, the risk of preterm birth remained elevated to a similar degree: aRR 2.6 (95%CI 1.9-3.7), aRD 10.0% (95%CI 4.8-15.3). The risk of other adverse perinatal outcomes was also higher, including the risk of chromosomal abnormalities other than trisomies 21 and 18: aRR 81.1 (95%CI 69.4-94.8), aRD 34.0% (95%CI 29.2-38.8). Pregnancies with double-positive results were also less likely to result in a live birth, even when excluding all diagnosed chromosomal abnormalities; and at increased risk of adverse perinatal outcomes for those resulting in a live birth. CONCLUSION: Although rare, double-positive multiple marker screening results are associated with an increased risk of preterm birth and other adverse perinatal outcomes, even when excluding all identified chromosomal abnormalities.