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Background The association between Institute of Medicine (IOM) guidelines and pregnancy outcomes across ethnicities is uncertain. We evaluated the associations of gestational weight gain (GWG) outside 2009 IOM guidelines, with maternal and infant outcomes across the USA, western Europe and east Asia, with subgroup analyses in Asia. The aim was to explore ethnic differences in maternal prepregnancy body mass index (BMI), GWG and health outcomes across these regions. Methods Systematic review, meta-analysis and meta-regression of observational studies were used for the study. MEDLINE, MEDLINE In-Process, Embase and all Evidence-Based Medicine (EBM) Reviews were searched from 1999 to 2017. Studies were stratified by prepregnancy BMI category and total pregnancy GWG. Odds ratio (ORs) 95% confidence intervals (CI) applied recommended GWG within each BMI category as the reference. Primary outcomes were small for gestational age (SGA), preterm birth and large for gestational age (LGA). Secondary outcomes were macrosomia, caesarean section and gestational diabetes. Results Overall, 5874 studies were identified and 23 were included ( n  = 1,309,136). Prepregnancy overweight/obesity in the USA, Europe and Asia was measured at 42%, 30% and 10% respectively, with underweight 5%, 3% and 17%. GWG below guidelines in the USA, Europe and Asia was 21%, 18% and 31%, and above was 51%, 51% and 37% respectively. Applying regional BMI categories in Asia showed GWG above guidelines (51%) was similar to that in the USA and Europe. GWG below guidelines was associated with a higher risk of SGA (USA/Europe [OR 1.51; CI 1.39, 1.63]; Asia [1.63; 1.45, 1.82]) and preterm birth (USA/Europe [1.35; 1.17, 1.56]; Asia [1.06; 0.78, 1.44]) than GWG within guidelines. GWG above guidelines was associated with a higher risk of LGA (USA/Europe [1.93; 1.81, 2.06]; Asia [1.68; 1.51 , 1.87]), macrosomia (USA/Europe [1.87; 1.70, 2.06]; Asia [2.18; 1.91, 2.49]) and caesarean (USA/Europe [1.26; 1.21, 1.33]; Asia [1.37; 1.30, 1.45]). Risks remained elevated when regional BMI categories were applied for GWG recommendations. More women in Asia were categorised as having GWG below guidelines using World Health Organization (WHO) (60%) compared to regional BMI categories (16%), yet WHO BMI was not accompanied by increased risks of adverse outcomes. Conclusions Women in the USA and western Europe have higher prepregnancy BMI and higher rates of GWG above guidelines than women in east Asia. However, when using regional BMI categories in east Asia, rates of GWG above guidelines are similar across the three continents. GWG outside guidelines is associated with adverse outcomes across all regions. If regional BMI categories are used in east Asia, IOM guidelines are applicable in the USA, western Europe and east Asia.

Objectives As welfare societies, Scandinavian countries share characteristics of equality related to healthcare access, gender, and social services. However, cultural and lifestyle variations create country-specific health differences. This meta-analysis assessed the prevalence of preterm birth (PTB) and its categories in Scandinavian countries. Methods A systematic search in key databases of literature published between 1990 and 2021 identified studies of the prevalence of PTB and its categories. Following the use of the Freeman–Tukey double arcsine transformation, a meta-analysis of weighted data was performed using the random-effects model and meta-prop method. Results We identified 109 observational studies that involved 86,420,188 live births. The overall pooled prevalence (PP) of PTB was 5.3% (PP = 5.3%, 95% confidence interval [CI] 5.1%, 5.5%). The highest prevalence was in Norway (PP = 6.2%, 95% CI 5.3%, 7.0%), followed by Sweden (PP = 5.3%, 95% CI 5.1%, 5.4%), Denmark (PP = 5.2%, 95% CI 4.9%, 5.3%), and Iceland (PP = 5.0%, 95% CI 4.4%, 5.7%). Finland had the lowest PTB rate (PP = 4.9%, 95% CI 4.7%, 5.1%). Conclusions The overall PP of PTB was 5.3%, with small variations among countries (4.9%–6.2%). The highest and lowest PPs of PTB were in Norway and Finland, respectively.

This retrospective cohort study evaluated the effects of complete, incomplete, and multiple courses of antenatal corticosteroids (ACS) on respiratory outcomes in twin preterm infants born between 28 + 0 and 36 + 6 weeks of gestation. A total of 1,115 neonates were analyzed. Primary outcomes included respiratory distress syndrome (RDS) and other adverse respiratory conditions. Infants exposed to more than one course of dexamethasone had higher requirements for CPAP support (aRR 1.400, 95% CI 1.098–1.785; P  = 0.007), increased lung atelectasis (aRR 2.456, 95% CI 1.052–5.730; P  = 0.038), and elevated rates of transient tachypnea of the newborn (TTNB) (aRR 1.682, 95% CI 1.194–2.368; P  = 0.003). Receiving two or three doses was associated with more severe birth asphyxia (aRR 1.881, 95% CI 1.062–3.331; P  = 0.030) and intraventricular hemorrhage (IVH) (aRR 2.001, 95% CI 1.150–3.481; P  = 0.014). While RDS rates did not significantly differ among groups, monochorionic diamniotic (MCDA) twins who received multiple ACS courses had a higher risk of RDS (aRR 1.854, 95% CI 1.126–3.053; P  = 0.015). These findings suggest that incomplete and repeated ACS courses may contribute to adverse respiratory outcomes, particularly in MCDA twins. Optimizing ACS administration is essential to improve neonatal outcomes in twin preterm pregnancies.

Preterm birth is a global health concern. Its adverse consequences may persist throughout the life course, exerting a potentially heavy burden on families, health systems, and societies. In high-income countries, the first children who benefited from improved care are now adults entering middle age. However, there is a clear gap in the knowledge regarding the long-term outcomes of individuals born preterm. This study aimed to assess the feasibility of recruiting and following up an e-cohort of adults born preterm worldwide and provide estimations of participation, characteristics of participants, the acceptability of questions, and the quality of data collected. We implemented a prospective, open, observational, and international e-cohort pilot study (Health of Adult People Born Preterm-an e-Cohort Pilot Study [HAPP-e]). Inclusion criteria were being an adult (aged ≥18 years), born preterm (<37 weeks of gestation), having internet access and an email address, and understanding at least 1 of the available languages. A large, multifaceted, and multilingual communication strategy was established. Between December 2019 and June 2021, inclusion and repeated data collection were performed using a secured web platform. We provided descriptive statistics regarding participation in the e-cohort, namely, the number of persons who registered on the platform, signed the consent form, initiated and completed the baseline questionnaire, and initiated and completed the follow-up questionnaire. We also described the main characteristics of the HAPP-e participants and provided an assessment of the quality of the data and the acceptability of sensitive questions. As of December 31, 2020, a total of 1004 persons had registered on the platform, leading to 527 accounts with a confirmed email and 333 signed consent forms. A total of 333 participants initiated the baseline questionnaire. All participants were invited to follow-up, and 35.7% (119/333) consented to participate, of whom 97.5% (116/119) initiated the follow-up questionnaire. Completion rates were very high both at baseline (296/333, 88.9%) and at follow-up (112/116, 96.6%). This sample of adults born preterm in 34 countries covered a wide range of sociodemographic and health characteristics. The gestational age at birth ranged from 23+6 to 36+6 weeks (median 32, IQR 29-35 weeks). Only 2.1% (7/333) of the participants had previously participated in a cohort of individuals born preterm. Women (252/333, 75.7%) and highly educated participants (235/327, 71.9%) were also overrepresented. Good quality data were collected thanks to validation controls implemented on the web platform. The acceptability of potentially sensitive questions was excellent, as very few participants chose the \"I prefer not to say\" option when available. Although we identified room for improvement in specific procedures, this pilot study confirmed the great potential for recruiting a large and diverse sample of adults born preterm worldwide, thereby advancing research on adults born preterm.

Aims: The aim of this study was to analyse associations between maternal country of birth and preterm birth among women giving birth in Norway. Methods: A population-based register study was conducted employing official national databases in Norway. All singleton births, with neonates without major anomalies, between 1999 and 2014 were included (N=910,752). We estimated odds ratios (ORs) for extremely preterm birth (<28 weeks gestation), very preterm birth (28–33 weeks gestation) and late preterm birth (34–36 weeks gestation) by maternal country of birth. We conducted multivariable regression analyses, adjusting for maternal, obstetric and socio-economic confounders. Results: For extremely preterm births (0.4% of the study population), women with an unknown country of birth (adjusted OR (aOR)=3.09; 95% confidence interval (CI) 2.26–4.22) and women born in sub-Saharan Africa (aOR=1.66; CI 1.40–1.96) had the highest ORs compared to Norwegian-born women. For very preterm births (1.2% of the study population), women with an unknown country of birth (aOR=1.72; CI 1.36–2.18) and women born in South Asia (aOR=1.48; CI 1.31–1.66) had the highest ORs. For late preterm births (3.8% of the study population), women born in East Asia Pacific/Oceania (aOR=1.33; CI 1.25–1.41) and South Asia (aOR=1.30; CI 1.21–1.39) had the highest ORs. Conclusions: After adjusting for maternal, obstetric and socio-economic risk factors, maternal country of birth remained significantly associated with preterm birth. Women with an unknown country of birth and women born in sub-Saharan Africa were found to be at increased risk of extremely preterm birth.

The results from epidemiologic studies linking blood folate concentrations, folic acid supplementation, or dietary folate to the risk of preterm birth are inconsistent. In this study, we aimed to summarize the available evidence on these associations. A systematic search of the PubMed/MEDLINE, Google Scholar, Web of Science, and Cochrane Library databases up to October 20, 2018 was performed and reference lists of retrieved articles were screened. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the highest vs. the lowest levels of folate concentrations, folic acid supplementation, and dietary folate were calculated using random-effects models. Subgroup analyses and univariate meta-regression were performed to explore the sources of heterogeneity. Ten studies (six prospective cohort studies and four case-control studies) were included on folate concentrations, 13 cohort studies were included about folic acid supplementation, and 4 cohort studies were included regarding dietary folate intake. Higher maternal folate levels were associated with a 28% reduction in the risk of preterm birth (OR 0.72, 95% CI 0.56-0.93). Higher folic acid supplementation was associated with 10% lower risk of preterm birth (OR 0.90, 95% CI 0.85-0.95). In addition, a significant negative association was observed between dietary folate intake and the risk of preterm birth (OR 0.68, 95% CI 0.55-0.84), but no significant relation was seen between dietary folate and the risk of spontaneous preterm birth (OR 0.89, 95% CI 0.57-1.41). In the subgroup analysis, higher maternal folate levels in the third trimester were associated with a lower risk of preterm birth (OR 0.58, 95% CI 0.36-0.94). To initiate taking folic acid supplementation early before conception was adversely associated with preterm birth risk (OR 0.89, 95% CI 0.83-0.95). In conclusion, higher maternal folate levels and folic acid supplementation were significantly associated with a lower risk of preterm birth. The limited data currently available suggest that dietary folate is associated with a significantly decreased risk of preterm birth.

Background Studies of preterm delivery after COVID-19 are often subject to selection bias and do not distinguish between early vs. late infection in pregnancy, nor between spontaneous vs. medically indicated preterm delivery. This study aimed to estimate the risk of preterm birth (overall, spontaneous, and indicated) after COVID-19 during pregnancy, while considering different levels of disease severity and timing. Methods Pregnant and recently pregnant people who were tested for or clinically diagnosed with COVID-19 during pregnancy enrolled in an international internet-based cohort study between June 2020 and July 2021. We used several analytic approaches to minimize confounding and immortal time bias, including multivariable regression, time-to-delivery models, and a case-time-control design. Results Among 14,264 eligible participants from 70 countries who did not report a pregnancy loss before 20 gestational weeks, 5893 had completed their pregnancies and reported delivery information; others were censored at time of their last follow-up. Participants with symptomatic COVID-19 before 20 weeks’ gestation had no increased risk of preterm delivery compared to those testing negative, with adjusted risks of 10.0% (95% CI 7.8, 12.0) vs. 9.8% (9.1, 10.5). Mild COVID-19 later in pregnancy was not clearly associated with preterm delivery. In contrast, severe COVID-19 after 20 weeks’ gestation led to an increase in preterm delivery compared to milder disease. For example, the risk ratio for preterm delivery comparing severe to mild/moderate COVID-19 at 35 weeks was 2.8 (2.0, 4.0); corresponding risk ratios for indicated and spontaneous preterm delivery were 3.7 (2.0, 7.0) and 2.3 (1.2, 3.9), respectively. Conclusions Severe COVID-19 late in pregnancy sharply increased the risk of preterm delivery compared to no COVID-19. This elevated risk was primarily due to an increase in medically indicated preterm deliveries, included preterm cesarean sections, although an increase in spontaneous preterm delivery was also observed. In contrast, mild or moderate COVID-19 conferred minimal risk, as did severe disease early in pregnancy.

ObjectiveTo determine the risk of recurrent spontaneous preterm birth (sPTB) following sPTB in singleton pregnancies.DesignSystematic review and meta-analysis using random effects models.Data sourcesAn electronic literature search was conducted in OVID Medline (1948–2017), Embase (1980–2017) and ClinicalTrials.gov (completed studies effective 2017), supplemented by hand-searching bibliographies of included studies, to find all studies with original data concerning recurrent sPTB.Study eligibility criteriaStudies had to include women with at least one spontaneous preterm singleton live birth (<37 weeks) and at least one subsequent pregnancy resulting in a singleton live birth. The Newcastle-Ottawa Scale was used to assess study quality.ResultsOverall, 32 articles involving 55 197 women, met all inclusion criteria. Generally studies were well conducted and had a low risk of bias. The absolute risk of recurrent sPTB at <37 weeks’ gestation was 30% (95% CI 27% to 34%). The risk of recurrence due to preterm premature rupture of membranes (PPROM) at <37 weeks gestation was 7% (95% CI 6% to 9%), while the risk of recurrence due to preterm labour (PTL) at <37 weeks gestation was 23% (95% CI 13% to 33%).ConclusionsThe risk of recurrent sPTB is high and is influenced by the underlying clinical pathway leading to the birth. This information is important for clinicians when discussing the recurrence risk of sPTB with their patients.

Background Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. Methods We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. Results In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P  = 0.026) and persisted following membrane rupture (31%, P  = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P  = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. Conclusions Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.

This study aimed to examine the trimester-specific association of maternal prenatal physical activities (PA) with risk of preterm birth (PTB). We recruited 2080 women during the first trimester and conducted follow-ups during the second and third trimesters and at birth. We assessed maternal PA during each trimester and calculated a cumulative PA score range from 0 to 3, with a higher score reflecting higher frequency and a sustained high level of PA over pregnancy. Lower risks of PTB were observed among women who had higher PA levels during the first [tertile 3 (T3) vs. tertile 1 (T1): odds ratio (OR) = 0.48; 95% confidence interval (CI): 0.32–0.71, P for trend = 0.003], second (T3 vs. T1: OR = 0.34; 95% CI: 0.22–0.52, P for trend < 0.001), and third trimesters (T3 vs. T1: OR = 0.28; 95% CI: 0.18–0.45, P for trend = 0.008), respectively. A higher prenatal cumulative PA score significantly correlated with a lower risk of PTB (3 vs. 0: OR = 0.24; 95% CI: 0.11–0.54, P for trend < 0.001) and iatrogenic preterm birth (3 vs. 0: OR = 0.23; 95% CI: 0.09–0.59, P for trend < 0.001) in a dose–response-dependent manner, but not with spontaneous preterm birth. These findings support the necessity of guiding the maternal PA from early pregnancy and highlight the importance of sustained PA to prevent PTB.