RESUMEN
BACKGROUND: Vaccination against respiratory syncytial virus (RSV) during pregnancy may protect infants from RSV disease. Efficacy and safety data on a candidate RSV prefusion F protein-based maternal vaccine (RSVPreF3-Mat) are needed. METHODS: We conducted a phase 3 trial involving pregnant women 18 to 49 years of age to assess the efficacy and safety of RSVPreF3-Mat. The women were randomly assigned in a 2:1 ratio to receive RSVPreF3-Mat or placebo between 24 weeks 0 days and 34 weeks 0 days of gestation. The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract disease in infants from birth to 6 months of age and safety in infants from birth to 12 months of age. After the observation of a higher risk of preterm birth in the vaccine group than in the placebo group, enrollment and vaccination were stopped early, and exploratory analyses of the safety signal of preterm birth were performed. RESULTS: The analyses included 5328 pregnant women and 5233 infants; the target enrollment of approximately 10,000 pregnant women and their infants was not reached because enrollment was stopped early. A total of 3426 infants in the vaccine group and 1711 infants in the placebo group were followed from birth to 6 months of age; 16 and 24 infants, respectively, had any medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 65.5%; 95% credible interval, 37.5 to 82.0), and 8 and 14, respectively, had severe medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 69.0%; 95% credible interval, 33.0 to 87.6). Preterm birth occurred in 6.8% of the infants (237 of 3494) in the vaccine group and in 4.9% of those (86 of 1739) in the placebo group (relative risk, 1.37; 95% confidence interval [CI], 1.08 to 1.74; P = 0.01); neonatal death occurred in 0.4% (13 of 3494) and 0.2% (3 of 1739), respectively (relative risk, 2.16; 95% CI, 0.62 to 7.56; P = 0.23), an imbalance probably attributable to the greater percentage of preterm births in the vaccine group. No other safety signal was observed. CONCLUSIONS: The results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT04605159.).
Asunto(s)
Nacimiento Prematuro , Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/etiología , Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Vacunas contra Virus Sincitial Respiratorio/efectos adversos , Vacunas contra Virus Sincitial Respiratorio/uso terapéutico , Enfermedades Respiratorias/prevención & control , Enfermedades Respiratorias/virología , Eficacia de las Vacunas , Resultado del Tratamiento , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , RiesgoRESUMEN
BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is the most common obstetric liver disorder and is associated with an increased risk of iatrogenic preterm birth and adverse infant outcomes. Hence, there are several plausible pathways through which ICP could affect offspring neurodevelopment. However, to the best of our knowledge, no studies have investigated these associations. Thus, we aimed to determine whether ICP is associated with offspring neurodevelopmental conditions. METHODS AND FINDINGS: In this Swedish register-based cohort study, we included singleton non-adopted children born in Sweden between the 1st of January 1987 and the 31st of December 2010, who were resident in Sweden >5 years, with no missing covariate information, which we followed until the 31st of December 2016. Maternal ICP diagnosis and the date of the initial diagnosis during pregnancy were obtained from the National Patient Register. Offspring diagnoses of attention deficit/hyperactivity disorder (ADHD), autism, or intellectual disability were obtained from the National Patient Register, and the dispensation of ADHD medications were obtained from the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression while controlling for observed confounders and unobserved confounders shared among full siblings and maternal full cousins. A total of 2,375,856 children were included in the study; 81.6% of them were of Nordic origin, and 51.4% were male. Of these, 10,378 (0.44%) were exposed to ICP. During a median of 18 years follow-up (interquartile range 11 to 24), 143,746 (6.05%) of children were diagnosed with a neurodevelopmental condition. After adjusting for child's sex, birth year, birth month, maternal age, highest parental education level, maternal birth country, birth order, maternal psychiatric history, ICP was associated with increased odds of offspring neurodevelopmental conditions (OR 1.22, 95% CI 1.13 to 1.31), particularly among those exposed to early-onset ICP (OR 2.38, 95% CI 1.71 to 3.30) as compared to ICP diagnosed after reaching term (≥37 weeks of gestation) (OR 1.08, 95% CI 0.97 to 1.20). The findings of early-onset ICP were consistent in family-based analyses. Within-family comparisons of full maternal cousins yielded an OR of 2.99 (95% CI 1.48 to 6.04), and comparisons of full siblings showed an OR of 1.92 (95% CI 0.92 to 4.02), though the latter was less precise. The findings were consistent across specific neurodevelopmental conditions and different analytical approaches. The primary limitations of this study included its observational design, the absence of data on ICP therapeutics, and the lack of bile acid measures. CONCLUSIONS: In this study, we observed that exposure to ICP during gestation is associated with an increased likelihood of neurodevelopmental conditions in offspring, particularly in cases of early-onset ICP. Further studies are warranted to better understand the role of early-ICP in offspring neurodevelopment.
Asunto(s)
Colestasis Intrahepática , Complicaciones del Embarazo , Nacimiento Prematuro , Efectos Tardíos de la Exposición Prenatal , Embarazo , Niño , Femenino , Lactante , Humanos , Masculino , Recién Nacido , Estudios de Cohortes , Suecia/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiologíaRESUMEN
Individualized pre-pregnancy counseling and antenatal care for women with chronic kidney disease (CKD) require disease-specific data. Here, we investigated pregnancy outcomes and long-term kidney function in women with COL4A3-5 related disease (Alport Syndrome, (AS)) in a large multicenter cohort. The ALPART-network (mAternaL and fetal PregnAncy outcomes of women with AlpoRT syndrome), an international collaboration of 17 centers, retrospectively investigated COL4A3-5 related disease pregnancies after the 20th week. Outcomes were stratified per inheritance pattern (X-Linked AS (XLAS)), Autosomal Dominant AS (ADAS), or Autosomal Recessive AS (ARAS)). The influence of pregnancy on estimated glomerular filtration rate (eGFR)-slope was assessed in 192 pregnancies encompassing 116 women (121 with XLAS, 47 with ADAS, and 12 with ARAS). Median eGFR pre-pregnancy was over 90ml/min/1.73m2. Neonatal outcomes were favorable: 100% live births, median gestational age 39.0 weeks and mean birth weight 3135 grams. Gestational hypertension occurred during 23% of pregnancies (reference: 'general' CKD G1-G2 pregnancies incidence is 4-20%) and preeclampsia in 20%. The mean eGFR declined after pregnancy but remained within normal range (over 90ml/min/1.73m2). Pregnancy did not significantly affect eGFR-slope (pre-pregnancy ß=-1.030, post-pregnancy ß=-1.349). ARAS-pregnancies demonstrated less favorable outcomes (early preterm birth incidence 3/11 (27%)). ARAS was a significant independent predictor for lower birth weight and shorter duration of pregnancy, next to the classic predictors (pre-pregnancy kidney function, proteinuria, and chronic hypertension) though missing proteinuria values and the small ARAS-sample hindered analysis. This is the largest study to date on AS and pregnancy with reassuring results for mild AS, though inheritance patterns could be considered in counseling next to classic risk factors. Thus, our findings support personalized reproductive care and highlight the importance of investigating kidney disease-specific pregnancy outcomes.
Asunto(s)
Nefritis Hereditaria , Complicaciones del Embarazo , Nacimiento Prematuro , Insuficiencia Renal Crónica , Femenino , Humanos , Embarazo , Recién Nacido , Lactante , Resultado del Embarazo/epidemiología , Nefritis Hereditaria/genética , Peso al Nacer , Estudios Retrospectivos , Nacimiento Prematuro/etiología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/genética , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/genética , Proteinuria , ConsejoRESUMEN
BACKGROUND: Interpregnancy interval (IPI) is associated with a variety of adverse maternal and infant outcomes. However, reports of its associations with early infant neurodevelopment are limited and the mechanisms of this association have not been elucidated. Maternal-fetal glucose metabolism has been shown to be associated with infant neurodevelopmental. The objective of this study was to determine whether this metabolism plays a role in the relationship between IPI and neurodevelopment. METHODS: This prospective birth cohort study included 2599 mother-infant pairs. The IPI was calculated by subtracting the gestational age of the current pregnancy from the interval at the end of the previous pregnancy. Neurodevelopmental outcomes at 12 months in infants were assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). Maternal fasting venous blood was collected at 24-28 weeks and cord blood was collected at delivery. The association between IPI and neurodevelopment was determined by logistic regression. Mediation and sensitivity analyses were also conducted. RESULTS: In our cohort, 14.0% had an IPI < 12 months. IPI < 12 months increased the failure of the communication domain, fine motor domain, and personal social domain of the ASQ (relative risks (RRs) with 95% confidence interval (CI): 1.73 [1.11,2.70]; 1.73 [1.10,2.72]; 1.51 [1.00,2.29]). Maternal homeostasis model assessment of insulin resistance (HOMA-IR) and cord blood C-peptide was significantly associated with failure in the communication domain [RRs with 95% CI: 1.15 (1.02, 1.31); 2.15 (1.26, 3.67)]. The proportion of the association between IPI and failure of the communication domain risk mediated by maternal HOMA-IR and cord blood C-peptide was 14.4%. CONCLUSIONS: IPI < 12 months was associated with failing the communication domain in infants. Maternal-fetal glucose metabolism abnormality may partially explain the risk of neurodevelopmental delay caused by short IPI.
Asunto(s)
Nacimiento Prematuro , Embarazo , Lactante , Femenino , Humanos , Estudios de Cohortes , Nacimiento Prematuro/etiología , Intervalo entre Nacimientos , Péptido C , Estudios Prospectivos , GlucosaRESUMEN
BACKGROUND: Preterm birth (PTB) is a leading cause of child morbidity and mortality. Evidence suggests an increased risk with both maternal underweight and obesity, with some studies suggesting underweight might be a greater factor in spontaneous PTB (SPTB) and that the relationship might vary by parity. Previous studies have largely explored established body mass index (BMI) categories. Our aim was to compare associations of maternal pre-pregnancy BMI with any PTB, SPTB and medically indicated PTB (MPTB) among nulliparous and parous women across populations with differing characteristics, and to identify the optimal BMI with lowest risk for these outcomes. METHODS: We used three UK datasets, two USA datasets and one each from South Australia, Norway and Denmark, together including just under 29 million pregnancies resulting in a live birth or stillbirth after 24 completed weeks gestation. Fractional polynomial multivariable logistic regression was used to examine the relationship of maternal BMI with any PTB, SPTB and MPTB, among nulliparous and parous women separately. The results were combined using a random effects meta-analysis. The estimated BMI at which risk was lowest was calculated via differentiation and a 95% confidence interval (CI) obtained using bootstrapping. RESULTS: We found non-linear associations between BMI and all three outcomes, across all datasets. The adjusted risk of any PTB and MPTB was elevated at both low and high BMIs, whereas the risk of SPTB was increased at lower levels of BMI but remained low or increased only slightly with higher BMI. In the meta-analysed data, the lowest risk of any PTB was at a BMI of 22.5 kg/m2 (95% CI 21.5, 23.5) among nulliparous women and 25.9 kg/m2 (95% CI 24.1, 31.7) among multiparous women, with values of 20.4 kg/m2 (20.0, 21.1) and 22.2 kg/m2 (21.1, 24.3), respectively, for MPTB; for SPTB, the risk remained roughly largely constant above a BMI of around 25-30 kg/m2 regardless of parity. CONCLUSIONS: Consistency of findings across different populations, despite differences between them in terms of the time period covered, the BMI distribution, missing data and control for key confounders, suggests that severe under- and overweight may play a role in PTB risk.
Asunto(s)
Índice de Masa Corporal , Nacimiento Prematuro , Femenino , Humanos , Recién Nacido , Embarazo , Paridad , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Factores de Riesgo , Delgadez , ObesidadRESUMEN
BACKGROUND: Prenatal exposure to intrauterine inflammation (IUI) is a crucial event in preterm birth (PTB) pathophysiology, increasing the incidence of neurodevelopmental disorders. Gut microbiota and metabolite profile alterations have been reported to be involved in PTB pathophysiology. METHOD AND RESULTS: In this study, IUI-exposed PTB mouse model was established and verified by PTB rate and other perinatal adverse reactions; LPS-indued IUI significantly increased the rates of PTB, apoptosis and inflammation in placenta tissue samples. LPS-induced IUI caused no significant differences in species richness and evenness but significantly altered the species abundance distribution. Non-targeted metabolomics analysis indicated that the metabolite profile of the preterm mice was altered, and differential metabolites were associated with signaling pathways including pyruvate metabolism. Furthermore, a significant positive correlation between Parasutterella excrementihominis and S4572761 (Nb-p-coumaroyltryptamine) and Mreference-1264 (pyruvic acid), respectively, was observed. Lastly, pyruvic acid treatment partially improved LPS-induced IUI phenotypes and decreased PTB rates and decreased the apoptosis and inflammation in placenta tissue samples. CONCLUSION: This study revealed an association among gut microbiota dysbiosis, metabolite profile alterations, and LPS-induced IUI and PTB in mice models. Our investigation revealed the possible involvement of gut microbiota in the pathophysiology of LPS-induced IUI and PTB, which might be mediated by metabolites such as pyruvic acid. Future studies should be conducted to verify the findings through larger sample-sized animal studies and clinical investigations.
Asunto(s)
Microbioma Gastrointestinal , Nacimiento Prematuro , Recién Nacido , Embarazo , Humanos , Femenino , Animales , Ratones , Lipopolisacáridos/farmacología , Nacimiento Prematuro/etiología , Ácido Pirúvico/efectos adversos , Inflamación/metabolismo , Inseminación ArtificialRESUMEN
STUDY QUESTION: Are there significant associations existing between parental age differences and adverse perinatal outcomes? SUMMARY ANSWER: Large differences in parental age are associated with adverse perinatal outcomes, particularly with older mothers paired with younger fathers. WHAT IS KNOWN ALREADY: The association between advanced maternal age and perinatal outcomes is well-documented with women over 35 years showing an increased risk of several adverse outcomes. Other studies have identified potential associations between advanced paternal age and adverse perinatal outcomes. STUDY DESIGN, SIZE, DURATION: A historical (retrospective) cohort analysis was performed utilizing a multivariable logistic regression model to evaluate the association between varying differences in parental age and adverse perinatal outcomes while controlling for demographic and health-related covariates. Data were compiled from the National Vital Statistics System for 20 613 704 births between 2012 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Parental age differences, categorized into eleven 4-year intervals, were stratified by seven maternal age categories and evaluated for their associations with adverse perinatal outcomes. Main outcome measures included low birth weight, very low birth weight, preterm birth, very preterm birth, small size for gestational age, low 5-min appearance, pulse, grimace, activity, and respiration score, congenital defects, and chromosomal anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: Increased parental age differences, in either direction, were associated with significant risks for all adverse outcomes, aside from congenital defects, even when controlling for maternal age. Restricting maternal age to the reference range of 25-29 years, infants born to fathers aged 9-12 years younger (n = 3773) had 27% (odds ratio (OR) 1.27, 95% CI, 1.17-1.37) higher odds of having any adverse perinatal outcome. Infants born to fathers aged >16 years older (n = 98 555) had 14% (OR 1.14, 95% CI, 1.12-1.16) higher odds of having any adverse perinatal outcome. LIMITATIONS, REASONS FOR CAUTION: Data extracted from US birth certificates may be compromised by errors in reporting or documentation. Information regarding the mother's socioeconomic status was estimated using proxy variables and may be susceptible to uncontrolled factors. Use of a pre-compiled dataset may potentially exclude additional maternal comorbidities that could impact perinatal outcomes. WIDER IMPLICATIONS OF FINDINGS: Older mothers paired with younger fathers demonstrated the highest risk, even when maternal age was below the threshold of 35 years. For the clinical setting, parental age differences should be considered alongside maternal and paternal age when assessing risks of adverse perinatal outcomes for potential parents. This is particularly relevant for older women with younger male partners as this may exacerbate the impact of advanced maternal age. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the NIH Research Fellowship T35 Training Grant. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.
Asunto(s)
Nacimiento Prematuro , Embarazo , Humanos , Masculino , Recién Nacido , Femenino , Anciano , Nacimiento Prematuro/etiología , Estudios Retrospectivos , Recién Nacido de Bajo Peso , Parto , MadresRESUMEN
STUDY QUESTION: Do characteristics of the lower uterine segment and cervix modify the risk of preterm delivery in uterus transplant (UTx) recipients? SUMMARY ANSWER: The cervical length showed little association with preterm delivery, however, cervical inflammation deserves further exploration as a cause of preterm delivery. WHAT IS KNOWN ALREADY: UTx recipients do not have the risk factors normally used to stratify pregnancies that would benefit from cervical length assessment. In addition, unique factors related to absent tissues, a different blood supply, inflammatory processes of rejection, cervical biopsies, and a different microbiome challenge the normal progressive remodeling of the cervix and thus cervical competence. STUDY DESIGN, SIZE, DURATION: This is a subanalysis of a clinical trial of 20 women undergoing uterus transplantation at Baylor University Medical Center from 2016 to 2020, in addition to two women who received transplantation outside of a research protocol at our institution through September 2022. In this report, the first 16 UTx recipients that achieved live birth are included. PARTICIPANTS/MATERIALS, SETTING, METHODS: The focus of this study was 20 pregnancies that reached the second trimester in 16 women following UTx. We analyzed recipient, transplant, and donor factors to determine if characteristics were associated with delivery outcome. We compared obstetrical outcomes, including planned versus unplanned delivery, by factors such as number of superior venous anastomoses, warm ischemia and cold ischemia times, donor factors including cesarean sections, cervical biopsy results, and cervical ultrasound results. MAIN RESULTS AND THE ROLE OF CHANCE: Planned term deliveries occurred in 44% (8/18) of live births. Of the preterm births, 30% (3/10) were planned and 70% (7/10) were unplanned. Unplanned deliveries occurred in women with spontaneous preterm labor, severe rejection, subchorionic hematoma, and placenta previa. Cervical length in UTx recipients averaged 33.5 mm at 24 weeks and 31.5 mm at 28 weeks, comparable to values from the general population. No relationship was seen between delivery outcome and number of veins used, ischemic time, or number of previous cesarean sections. LIMITATIONS, REASONS FOR CAUTION: The study's small size allows limited conclusions. The obstetric history of all donors was limited to mode of delivery. WIDER IMPLICATIONS OF THE FINDINGS: Cervical length measurements in the UTx population are not expected to deviate from those with a native uterus. While cervical length surveillance remains important, attention must be paid to the results of cervical biopsies which are obtained to monitor rejection. Inflammatory processes seem most predictive of preterm delivery. STUDY FUNDING/COMPETING INTEREST(S): No funding was provided for this study. The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT02656550.
Asunto(s)
Nacimiento Prematuro , Femenino , Humanos , Recién Nacido , Embarazo , Cuello del Útero/diagnóstico por imagen , Nacimiento Prematuro/etiología , Factores de Riesgo , Receptores de Trasplantes , Útero/diagnóstico por imagenRESUMEN
STUDY QUESTION: Is large for gestational age (LGA) observed in babies born after frozen embryo transfer (FET) associated with either the freezing technique or the endometrial preparation protocol? SUMMARY ANSWER: Artificial cycles are associated with a higher risk of LGA, with no difference in rate between the two freezing techniques (vitrification versus slow freezing) or embryo stage (cleaved embryo versus blastocyst). WHAT IS KNOWN ALREADY: Several studies have compared neonatal outcomes after fresh embryo transfer (ET) and FET and shown that FET is associated with improved neonatal outcomes, including reduced risks of preterm birth, low birthweight, and small for gestational age (SGA), when compared with fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology of this increased risk remains unclear; parental infertility, laboratory procedures (including embryo culture conditions and freezing-thawing processes), and endometrial preparation treatments might be involved. STUDY DESIGN, SIZE, DURATION: A multicentre epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national register of IVF from 2014 to 2018, including single deliveries resulting from fresh ET or FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres and included the vitrification media and devices, and the endometrial preparation protocols. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from 35 French ART centres, leading to the inclusion of a total of 72 789 fresh ET, 10 602 slow-freezing FET, and 39 062 vitrification FET. Main clinical outcomes were presented according to origin of the transferred embryos (fresh, slow frozen, or vitrified embryos) and endometrial preparations for FET (ovulatory or artificial cycles), comparing five different groups (fresh, slow freezing-ovulatory cycle, slow freezing-artificial cycle, vitrification-ovulatory cycle, and vitrification-artificial cycle). Foetal growth disorders were defined in live-born singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if <10th and ≥90th percentiles, respectively. Analyses were performed using linear mixed models with the ART centres as random effect. MAIN RESULTS AND THE ROLE OF CHANCE: Transfers led to, respectively, 19 006, 1798, and 9195 deliveries corresponding to delivery rates per transfer of 26.1%, 17.0%, and 23.5% after fresh ET, slow-freezing FET, and vitrification FET, respectively. FET cycles were performed in either ovulatory cycles (n = 21 704) or artificial cycles (n = 34 237), leading to 5910 and 10 322 pregnancies, respectively, and corresponding to pregnancy rates per transfer of 31.6% and 33.3%. A significantly higher rate of spontaneous miscarriage was observed in artificial cycles when compared with ovulatory cycles (33.3% versus 21.4%, P < 0.001, in slow freezing groups and 31.6% versus 21.8%, P < 0.001 in vitrification groups). Consequently, a lower delivery rate per transfer was observed in artificial cycles compared with ovulatory cycles both in slow freezing and vitrification groups (15.5% versus 18.9%, P < 0.001 and 22.8% versus 24.9%, P < 0.001, respectively). Among a total of 26 585 live-born singletons, 16 413 babies were born from fresh ET, 1644 from slow-freezing FET, and 8528 from vitrification FET. Birthweight was significantly higher in the FET groups than in the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared with the fresh ET group whatever the method used for embryo freezing. In a multivariable analysis, the risk of LGA following FET was significantly increased in artificial compared with ovulatory cycles. In contrast, the risk of LGA was not associated with either the freezing procedure (vitrification versus slow freezing) or the embryo stage (cleaved embryo versus blastocyst) at freezing. Regarding the vitrification method, the risk of LGA was not associated with either the vitrification medium used or the embryo stage. LIMITATIONS, REASONS FOR CAUTION: No data were available on maternal context, such as parity, BMI, infertility cause, or maternal comorbidities, in the French national database. In particular, we cannot exclude that the increased risk of LGA observed following FET with artificial cycles may, at least partially, be associated with a confounding effect of some maternal factors. No information about embryo culture and incubation conditions was available. Most of the vitrification techniques were performed using the same device and with two main vitrification media, limiting the validity of a comparison of risk for LGA according to the device or vitrification media used. WIDER IMPLICATIONS OF THE FINDINGS: Our results seem reassuring, since no potential foetal growth disorders following embryo vitrification in comparison with slow freezing were observed. Even if other factors are involved, the endometrial preparation treatment seems to have the greatest impact on LGA risk following FET. FET during ovulatory cycles could minimize the risk for foetal growth disorders. STUDY FUNDING/COMPETING INTEREST(S): This work has received funding from the French Biomedicine Agency (Grant number: 19AMP002). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
Asunto(s)
Infertilidad , Nacimiento Prematuro , Embarazo , Masculino , Femenino , Recién Nacido , Humanos , Peso al Nacer , Congelación , Estudios Retrospectivos , Criopreservación/métodos , Edad Gestacional , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Transferencia de Embrión/efectos adversos , Transferencia de Embrión/métodos , Índice de Embarazo , Infertilidad/etiología , Trastornos del Crecimiento/etiologíaRESUMEN
AIMS: Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age. METHODS: Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes. RESULTS: The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05). CONCLUSIONS: Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes.
Asunto(s)
Parálisis Cerebral , Corioamnionitis , Rotura Prematura de Membranas Fetales , Nacimiento Prematuro , Sepsis , Lactante , Recién Nacido , Humanos , Femenino , Embarazo , Recien Nacido Prematuro , Corioamnionitis/epidemiología , Corioamnionitis/etiología , Corioamnionitis/patología , Placenta/patología , Rotura Prematura de Membranas Fetales/patología , Parálisis Cerebral/complicaciones , Parálisis Cerebral/patología , Nacimiento Prematuro/etiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/patología , Factores de Riesgo , Edad Gestacional , Sepsis/complicaciones , Sepsis/patologíaRESUMEN
BACKGROUND: To evaluate the impact of embryo quality and quantity, specifically a poor quality embryo (PQE) in combination with a good quality embryo (GQE), by double embryo transfer (DET) on the live birth rate (LBR) and neonatal outcomes in patients undergoing frozen-thawed embryo transfer (FET) cycles. METHODS: A study on a cohort of women who underwent a total of 1462 frozen-thawed cleavage or blastocyst embryo transfer cycles with autologous oocytes was conducted between January 2018 and December 2021. To compare the outcomes between single embryo transfer (SET) with a GQE and DET with a GQE and a PQE, propensity score matching (PSM) was applied to control for potential confounders, and a generalized estimating equation (GEE) model was used to determine the association between the effect of an additional PQE and the outcomes. Subgroup analysis was also performed for patients stratified by female age. RESULTS: After PS matching, DET-GQE + PQE did not significantly alter the LBR (adjusted odds ratio [OR] 1.421, 95% CI 0.907-2.228) compared with SET-GQE in cleavage-stage embryo transfer but did increase the multiple birth rate (MBR, [OR] 3.917, 95% CI 1.189-12.911). However, in patients who underwent blastocyst-stage embryo transfer, adding a second PQE increased the live birth rate by 7.8% ([OR] 1.477, 95% CI 1.046-2.086) and the multiple birth rate by 19.6% ([OR] 28.355, 95% CI 3.926-204.790), and resulted in adverse neonatal outcomes. For patients who underwent cleavage-stage embryo transfer, transferring a PQE with a GQE led to a significant increase in the MBR ([OR] 4.724, 95% CI 1.121-19.913) in women under 35 years old but not in the LBR ([OR] 1.227, 95% CI 0.719-2.092). The increases in LBR and MBR for DET-GQE + PQE compared with SET-GQE in women older than 35 years were nonsignificant toward. For patients who underwent blastocyst-stage embryo transfer, DET-GQE + PQE had a greater LBR ([OR] 1.803, 95% CI 1.165-2.789), MBR ([OR] 24.185, 95% CI 3.285-178.062) and preterm birth rate (PBR, [OR] 4.092, 95% CI 1.153-14.518) than did SET-GQE in women under 35 years old, while no significant impact on the LBR ([OR] 1.053, 95% CI 0.589-1.884) or MBR (0% vs. 8.3%) was observed in women older than 35 years. CONCLUSIONS: The addition of a PQE has no significant benefit on the LBR but significantly increases the MBR in patients who underwent frozen-thawed cleavage-stage embryo transfer. However, for patients who underwent blastocyst-stage embryo transfer, DET-GQE + PQE resulted in an increase in both the LBR and MBR, which may lead to adverse neonatal outcomes. Thus, the benefits and risks of double blastocyst-stage embryo transfer should be balanced. In patients younger than 35 years, SET-GQE achieved satisfactory LBR either in cleavage-stage embryo transfer or blastocyst-stage embryo transfer, while DET-GQE + PQE resulted in a dramatically increased MBR. Considering the low LBR in women older than 35 years who underwent single cleavage-stage embryo transfer, selective single blastocyst-stage embryo transfer appears to be a more promising approach for reducing the risk of multiple live births and adverse neonatal outcomes.
Asunto(s)
Fertilización In Vitro , Nacimiento Prematuro , Embarazo , Femenino , Humanos , Recién Nacido , Adulto , Fertilización In Vitro/métodos , Nacimiento Prematuro/etiología , Transferencia de Embrión/métodos , Embarazo Múltiple , Transferencia de un Solo Embrión/efectos adversos , Nacimiento Vivo , Índice de Embarazo , Estudios RetrospectivosRESUMEN
BACKGROUND: Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. OBJECTIVE: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. STUDY DESIGN: This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. RESULTS: Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. CONCLUSION: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.
Asunto(s)
Ácidos Nucleicos Libres de Células , Síndrome de Down , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Largo Cráneo-Cadera , Resultado del Embarazo , Peso al Nacer , Estudios Retrospectivos , Nacimiento Prematuro/etiología , Primer Trimestre del Embarazo , Ultrasonografía Prenatal/efectos adversos , Gemelos Dicigóticos , Embarazo Gemelar , TrisomíaRESUMEN
BACKGROUND: Preterm labor and delivery is a major concern for patients with twin-to-twin transfusion syndrome undergoing fetoscopic laser surgery. A preoperative short cervix is a risk factor for preterm labor. Pessary placement is a short-acting intervention that may be useful to reduce this adverse event. OBJECTIVE: This study aimed to investigate the relationship between pessary placement and preterm delivery in monochorionic twin pregnancies with twin-to-twin transfusion syndrome and a short cervix before fetoscopic laser surgery. STUDY DESIGN: This was a retrospective study in 2 centers, including all pregnancies affected by twin-to-twin transfusion syndrome that underwent fetoscopic laser surgery with the Solomon technique between 2013 and 2022 (center A) and 2014 and 2022 (center B) with a preoperative cervical length below 25 mm. This study explored the correlation between cervical length and fetoscopic laser surgery-to-delivery interval following active or expectant management and compared perinatal outcomes between patients managed expectantly and patients managed with pessary placement, using multivariate analysis to control for potential confounders. Patients with a cervical length below 5 mm were not included in the comparative analysis. RESULTS: Of 685 patients, 134 met the inclusion criteria. Moreover, 21 patients were treated with a cervical cerclage and excluded from the analysis, leaving 113 patients for the final analysis. There was a significant negative correlation between cervical length at fetoscopic laser surgery and the risk of early delivery (adjusted odds ratio, 0.66; 95% confidence interval, 0.49-0.81; P<.001). The use of a pessary correlated with fewer patients delivering before 28 weeks of gestation (adjusted odds ratio, 0.28; 95% confidence interval, 0.09-0.75), fewer double neonatal demise (adjusted odds ratio, 0.2; 95% confidence interval, 0.05-0.75). Posthoc subgroup analysis suggested that these improvements were essentially noticeable for cervical lengths between 5 and 18 mm, where pessary placement was associated with an increased fetoscopic laser surgery-to-delivery interval (+24 days; 95% confidence interval, 0.86-42; P=.042) and later gestational age at delivery (+3.3 weeks; 95% confidence interval, 0.86-42; P=.035). CONCLUSION: Patients with a moderately shortened cervix, between 5 and 18 mm, may benefit from pessary placement after fetoscopic surgery for twin-to-twin transfusion syndrome, resulting in a reduction of adverse neonatal outcomes, double neonatal demise, and severe preterm delivery.
Asunto(s)
Transfusión Feto-Fetal , Terapia por Láser , Trabajo de Parto Prematuro , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Transfusión Feto-Fetal/cirugía , Transfusión Feto-Fetal/complicaciones , Cuello del Útero/cirugía , Estudios Retrospectivos , Pesarios/efectos adversos , Fetoscopía/métodos , Embarazo GemelarRESUMEN
BACKGROUND: Although many studies suggested the benefit of smoking cessation among pregnant women in reducing the risk of preterm birth (PTB), the timing of the effect of the cessation remains inconclusive. OBJECTIVES: To examine the association of trimester-specific smoking cessation behaviours with PTB risk. METHODS: We included 199,453 live births in Western New York between 2004 and 2018. Based on self-reported cigarette smoking during preconception and in each trimester, we created six mutually exclusive groups: non-smokers, quitters in each trimester, those who smoked throughout pregnancy, and inconsistent smokers. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Poisson regression to examine the association between smoking cessation and PTB. Effect modification by illegal drug use, maternal age, race and ethnicity and pre-pregnancy body mass index (BMI) was investigated multiplicatively by ratio of relative risk and additively by relative excess risk due to interaction (RERI). RESULTS: Overall, 6.7% of women had a PTB; 14.1% smoked throughout pregnancy and 3.4%, 1.8% and 0.8% reported quitting smoking during the first, second and third trimesters, respectively. Compared to non-smokers, third-trimester cessation (RR 1.20, 95% CI 1.01, 1.43) and smoking throughout pregnancy (RR 1.27, 95% CI 1.21, 1.33) were associated with a higher PTB risk, while quitting smoking during the first or second trimester, or inconsistent smoking was not associated with PTB. A positive additive interaction was identified for maternal age and late smoking cessation or smoking throughout pregnancy on PTB risk (RERI 0.17, 95% CI 0.00, 0.36), and a negative interaction was observed for pre-pregnancy BMI ≥30 kg/m2 (ratio of relative risk 0.70, 95% CI 0.63, 0.78; RERI -0.42, 95% CI -0.56, -0.30). CONCLUSION: Compared to non-smokers, smoking throughout pregnancy and third-trimester smoking cessation are associated with an increased risk of PTB, while quitting before the third trimester may not increase PTB risk.
Asunto(s)
Fumar Cigarrillos , Trimestres del Embarazo , Nacimiento Prematuro , Cese del Hábito de Fumar , Humanos , Femenino , Embarazo , Cese del Hábito de Fumar/estadística & datos numéricos , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Adulto , New York/epidemiología , Adulto Joven , Fumar Cigarrillos/efectos adversos , Fumar Cigarrillos/epidemiología , Factores de Riesgo , Recién NacidoRESUMEN
BACKGROUND: Preterm birth affects between 7% and 8% of births in the UK and is a leading cause of infant mortality and childhood disability. Prevalence of preterm birth has been shown to have significant and consistent socioeconomic inequalities. OBJECTIVE: To estimate how much of the association between socioeconomic status (SES) and gestational age at birth is mediated by maternal smoking status and maternal body mass index (BMI). METHODS: Retrospective cohort study of a maternity hospital in the UK. The analysis included all singleton live births between April 2009 and March 2020 to mothers 18 years old and over, between 22 weeks and 43 weeks gestation. We estimate two measures of mediation for four low gestational age categories: (i) The proportion eliminated the percentage of the effect of SES on low gestational age at birth that would be eliminated by removing the mediators, through the Controlled Direct Effects estimated using serial log-binomial regressions; and (ii) The proportion mediated is the percentage of the effect removed by equalising the distribution of the mediators across socioeconomic groups, estimated using Interventional Disparity Measures calculated through Monte Carlo simulations. RESULTS: Overall, 81,219 births were included, with 63.7% low SES. The risk of extremely (0.3% of all births), very (0.7%) and moderately preterm birth (6.3%) was 1.71 (95% Confidence Interval [CI] 1.29, 2.31), 1.43 (95% CI 1.18, 1.73) and 1.26 (95% CI 1.19, 1.34) times higher in the low SES, compared to higher SES respectively. The proportion of this inequality eliminated by removing both maternal smoking and BMI was 43.4% for moderately preterm births. The proportion mediated for smoking was 33.9%, 43.0% and 48.4% respectively. CONCLUSIONS: Smoking during pregnancy is a key mediator of inequalities in preterm birth, representing an area for local action to reduce social inequalities in preterm birth.
Asunto(s)
Nacimiento Prematuro , Recién Nacido , Embarazo , Femenino , Humanos , Adolescente , Adulto , Niño , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Índice de Masa Corporal , Estudios Retrospectivos , Análisis de Mediación , Fumar/efectos adversos , Fumar/epidemiología , Factores SocioeconómicosRESUMEN
OBJECTIVE: There is a secular trend towards earlier age of menarche in the US and globally. Earlier age at menarche (AAM) has been associated with metabolic disorders that increase risk for preterm delivery (PTD), yet no studies in the US have investigated whether AAM influences risk of PTD. This study tested the hypothesis that AAM is associated with PTD. DESIGN: A case-control study. SETTING: The Boston Medical Center (BMC) in Boston, Massachusetts. POPULATION OR SAMPLE: 8264 mother-newborn dyads enrolled at birth at BMC between 1998 and 2019, of which 2242 mothers had PTD (cases) and 6022 did not have PTD (controls). METHODS: Multivariable-adjusted logistic regression models and restricted cubic splines were used to examine the association between AAM and risk of PTD. The combined impact of AAM and age at delivery on the risk of PTD was also examined. MAIN OUTCOME MEASURES: Preterm delivery and gestational age (GA) was defined by maternal last menstrual period and early ultrasound documented in medical records. RESULTS: Maternal age at delivery was 28.1 ± 6.5 years and AAM was 12.85 ± 1.86 years. Multivariable-adjusted cubic spline suggested an inverse dose-response association of AAM with odds of PTD and, consistently, a positive association with GA. A 1-year earlier AAM was associated with 5% (95% CI 2%-8%) higher odds of PTD, after adjustment for maternal year of birth, parity, maternal place of birth, education, smoking status and Mediterranean-style diet score. The association between AAM and PTD was stronger among older mothers whose age at delivery was ≥35 years. CONCLUSIONS: Earlier AAM is associated with higher odds for PTD, and this association is stronger among women at advanced reproductive age.
Asunto(s)
Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Adulto , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Estudios de Casos y Controles , Madres , Menarquia , Edad MaternaRESUMEN
OBJECTIVE: To explore the relationship between occupational heat exposure, physiological heat strain indicators and adverse outcomes in pregnant women. DESIGN: Prospective cohort. SETTING: Workplaces in Tamil Nadu, India. SAMPLE: A cohort of 800 pregnant women engaged in moderate to heavy physical work in 2017-2019 and 2021-2022. METHODS: Participants were recruited at between 8 and 14 weeks of gestation. Occupational heat exposure and heat strain indicators were captured each trimester. 'Heat exposed' was defined as heat stress exceeding the threshold limit value (TLV) for safe manual work (with maximum wet-bulb globe temperatures of 27.5°C for a heavy workload and 28.0°C for a moderate workload). Physiological heat strain indicators (HSIs) such as core body temperature (CBT) and urine specific gravity (USG) were measured before and after each shift. Heat-related health symptoms were captured using the modified HOTHAPS questionnaire. MAIN OUTCOME MEASURES: The main outcome measures included (1) a composite measure of any adverse pregnancy outcome (APO) during pregnancy (including miscarriage, preterm birth, low birthweight, stillbirth, intrauterine growth restriction and birth defects), (2) a composite measure of adverse outcomes at birth (3) and miscarriage. RESULTS: Of the 800 participants, 47.3% had high occupational heat exposure. A rise in CBT was recorded in 17.4% of exposed workers, and 29.6% of workers experienced moderate dehydration (USG ≥ 1.020). Heat-exposed women had a doubled risk of miscarriage (adjusted odds ratio, aOR 2.4; 95% confidence interval, 95% CI 1.0-5.7). High occupational heat exposure was associated with an increased risk of any adverse pregnancy and foetal outcome (aOR 2.3; 95% CI 1.4-3.8) and adverse outcome at birth (aOR 2.0; 95% CI 1.2-3.3). CONCLUSIONS: High occupational heat exposure is associated with HSIs and adverse pregnancy outcomes in India.
Asunto(s)
Aborto Espontáneo , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Estudios Prospectivos , India/epidemiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Resultado del Embarazo/epidemiología , Respuesta al Choque TérmicoRESUMEN
OBJECTIVE: To investigate the association between ambient temperature and preterm birth (PTB) and to estimate the population attributable fraction (PAF) of PTBs due to low and high temperatures. DESIGN: Time-stratified case-crossover design. SETTING: Japan (46 prefectures, excluding Okinawa), 2011-2020. SAMPLE: 214 050 PTBs registered in the Japan Perinatal Registry Network database among 1 908 168 singleton live births. METHODS: A quasi-Poisson regression model with a distributed lag nonlinear model was employed to assess the associations between daily mean temperature and PTBs for a lag of 0-27 days in each prefecture. A random effects meta-analysis was conducted by combining effect estimates from the 46 prefectures to estimate pooled relative risks (RRs). The PAFs of the PTBs due to below or above the mean of the 46 median temperatures (16.0°C) were calculated. MAIN OUTCOME MEASURES: Preterm singleton live births. RESULTS: The association between daily mean temperature and PTB risk exhibited a U-shaped curve. The adjusted RRs were 1.15 (95% confidence interval [CI] 1.05-1.25) at the mean of the 1st percentiles (0.8°C) and 1.08 (95% CI 1.00-1.17) at the mean of the 99th percentiles (30.2°C) of 46 prefectures, with 16.0°C as the reference temperature. Approximately 2.3% (95% CI 0.6-4.0) of PTBs were attributable to low temperatures. CONCLUSIONS: Both low and possibly high temperatures were associated with an increased risk of PTBs. These findings may help to inform preventive measures for pregnant women.
Asunto(s)
Nacimiento Prematuro , Recién Nacido , Humanos , Femenino , Embarazo , Temperatura , Estudios Cruzados , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Riesgo , Dinámicas no Lineales , Calor , FríoRESUMEN
OBJECTIVE: To compare the risk of adverse pregnancy outcomes between twin-born and singleton-born women. We also evaluated whether in utero exposure to pre-eclampsia or preterm delivery affected adverse pregnancy outcomes in women's own pregnancies. DESIGN: Population-based cohort study. SETTING: Medical Birth Registry of Norway 1967-2020. POPULATION: 9184 twin-born and 492 894 singleton-born women during 1967-2005, with their later pregnancies registered during 1981-2020. METHODS: Data from an individual's birth were linked to their later pregnancies. We used generalised linear models with log link binomial distribution to obtain exponentiated regression coefficients that estimated relative risks (RRs) with 95% confidence intervals (CIs) for associations between twin- or singleton-born women and later adverse pregnancy outcomes. MAIN OUTCOME MEASURES: Pre-eclampsia, preterm delivery or perinatal loss in twin-born compared with singleton-born women. RESULTS: There was no increased risk for adverse outcomes in twin-born compared with singleton-born women: adjusted RRs for pre-eclampsia were 1.00 (95% CI 0.93-1.09), for preterm delivery 0.96 (95% CI 0.90-1.02) and for perinatal loss 1.00 (95% CI 0.84-1.18). Compared with singleton-born women exposed to pre-eclampsia in utero, twin-born women exposed to pre-eclampsia had lower risk of adverse outcomes in their own pregnancies; the aRR for pre-eclampsia was 0.73 (95% CI 0.58-0.91) and for preterm delivery was 0.71 (95% CI 0.56-0.90). Compared with preterm singleton-born women, preterm twin-born women did not differ in terms of risk of pre-eclampsia (aRR 1.05, 95% CI 0.92-1.21) or perinatal loss (aRR 0.99, 95% CI 0.71-1.37) and had reduced risk of preterm delivery (RR 0.83, 95% CI 0.74-0.94). CONCLUSIONS: Twin-born women did not differ from singleton-born women in terms of risk of adverse pregnancy outcomes. Twin-born women exposed to pre-eclampsia in utero, had a lower risk of pre-eclampsia and preterm delivery compared with singleton-born women exposed to pre-eclampsia.
Asunto(s)
Preeclampsia , Nacimiento Prematuro , Recién Nacido , Embarazo , Femenino , Humanos , Resultado del Embarazo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Estudios de Cohortes , Preeclampsia/epidemiología , Preeclampsia/etiología , Embarazo Gemelar , Estudios RetrospectivosRESUMEN
Epidemiological data provide varying degrees of evidence for associations between prenatal exposure to ambient air pollutants and adverse birth outcomes (suboptimal measures of fetal growth, preterm birth and stillbirth). To assess further certainty of effects, this review examines the experimental literature base to identify mechanisms by which air pollution (particulate matter, nitrogen dioxide and ozone) could cause adverse effects on the developing fetus. It likely that this environmental insult impacts multiple biological pathways important for sustaining a healthy pregnancy, depending upon the composition of the pollutant mixture and the exposure window owing to changes in physiologic maturity of the placenta, its circulations and the fetus as pregnancy ensues. The current body of evidence indicates that the placenta is a target tissue, impacted by a variety of critical processes including nitrosative/oxidative stress, inflammation, endocrine disruption, epigenetic changes, as well as vascular dysregulation of the maternal-fetal unit. All of the above can disturb placental function and, as a consequence, could contribute to compromised fetal growth as well increasing the risk of stillbirth. Furthermore, given that there is often an increased inflammatory response associated with preterm labour, inflammation is a plausible mechanism mediating the effects of air pollution on premature delivery. In the light of increased urbanisation and an ever-changing climate, both of which increase ambient air pollution and negatively affect vulnerable populations such as pregnant individuals, it is hoped that the collective evidence may contribute to decisions taken to strengthen air quality policies, reductions in exposure to air pollution and subsequent improvements in the health of those not yet born.