Impact of early continuous positive airway pressure in the delivery room (DR-CPAP) on neonates < 1500 g in a low-resource setting: a protocol for a pilot feasibility and acceptability randomized controlled trial.

BACKGROUND: Preterm birth is the leading cause of childhood mortality, and respiratory distress syndrome is the predominant cause of these deaths. Early continuous positive airway pressure is effective in high-resource settings, reducing the rate of continuous positive airway pressure failure, and the need for mechanical ventilation and surfactant. However, most deaths in preterm infants occur in low-resource settings without access to mechanical ventilation or surfactant. We hypothesize that in such settings, early continuous positive airway pressure will reduce the rate of failure and therefore preterm mortality. METHODS: This is a mixed methods feasibility and acceptability, single-center pilot randomized control trial of early continuous positive airway pressure among infants with birthweight 800-1500 g. There are two parallel arms: (i) application of continuous positive airway pressure; with optional oxygen when indicated; applied in the delivery room within 15 min of birth; transitioning to bubble continuous positive airway pressure after admission to the neonatal unit if Downes Score ≥ 4 (intervention), (ii) supplementary oxygen at delivery when indicated; transitioning to bubble continuous positive airways pressure after admission to the neonatal unit if Downes Score ≥ 4 (control). A two-stage consent process (verbal consent during labor, followed by full written consent within 24 h of birth) and a low-cost third-party allocation process for randomization will be piloted. We will use focus group discussions and key informant interviews to explore the acceptability of the intervention, two-stage consent process, and trial design. We will interview healthcare workers, mothers, and caregivers of preterm infants. Feasibility will be assessed by the proportion of infants randomized within 15 min of delivery; the proportion of infants in the intervention arm receiving CPAP within 15 min of delivery; and the proportion of infants with primary and secondary outcomes measured successfully. DISCUSSION: This pilot trial will enhance our understanding of methods and techniques that can enable emergency neonatal research to be carried out effectively, affordably, and acceptably in low-resource settings. This mixed-methods approach will allow a comprehensive exploration of parental and healthcare worker perceptions, experiences, and acceptance of the intervention and trial design. TRIAL REGISTRATION: The study is registered on the Pan African Clinical Trials Registry (PACTR) PACTR202208462613789. Registered 08 August 2022.  https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23888 .

Geographical disparities in temporal trends of low birth weight in Saskatchewan from 2002/2003 to 2021/2022: insights from a joinpoint regression analysis.

Low birth weight (LBW) is an important public health indicator that is associated with various negative health outcomes in infants. To effectively implement interventions that would improve health outcomes in children, it is important to understand both the historical trends and current levels of LBW rates. In this study, trends and regional differences in LBW rates in Saskatchewan from 2002/2003 to 2021/2022 were assessed. A joinpoint regression analysis was conducted using historical LBW rates, obtained from the Canadian Institute for Health Information database. Data were analysed using average percent change and average annual percent change. Spatial patterns and trends were identified using a choropleth map. From a provincial and national rate of 5.2% in 2002/2003, the LBW rate in Saskatchewan increased to 6.5% in 2021/2022, approaching the national rate of 6.8%. Over the 20-year period, average annual changes for Canada were 1.4% and 1.0% for Saskatchewan. There was a turning point in the study: 2004/2005 for Canada and 2011/2012 for Saskatchewan. Initially, Saskatchewan had stable LBW rates, increasing yearly by 0.1%, while the national rate was 5.7%. However, in recent years, Saskatchewan's rate increased to 1.8% annually, surpassing the national rate of 0.9%. Geographical differences were also observed within Saskatchewan, with the Far North region having the highest LBW rate (9.2%), and the Central West region having the lowest rate (4.3%) in 2021/2022. The Central East, Regina Qu'Appelle, and southern Saskatchewan saw significant upwards trends in LBW rates between 2015/2016 and 2021/2022. There is an increasing trend in LBW rates in Canada and Saskatchewan, as well as geographical disparities within the province. The geographical disparities in LBW rates underscore the need for tailored interventions in high-risk regions in the province.

Changes in social relationships from 26 to 34 years of age in adults born very preterm.

BACKGROUND: Very preterm and/or very low birthweight (VP/VLBW; <32 weeks' gestation and/or <1500 g birthweight) individuals rated their partner and peer relationships lower than term-born individuals in emerging adulthood, but their quality of relationships with parents has been rarely investigated. Moreover, it is unclear whether previously reported differences in social relationship characteristics persist or lessen from emerging to established adulthood. OBJECTIVES: To investigate changes in social relationship characteristics in VP/VLBW adults compared to term-born adults from 26 to 34 years and whether the association between VP/VLBW and social relationship characteristics varies according to sex. METHODS: In this prospective whole-population birth cohort study in South Bavaria, Germany, social relationship characteristics with parents, partners and peers, and overall social relationships across these domains were evaluated with a Life Course Interview at 26 and 34 years. Interview items related to these domains were extracted and scored as 0 (optimal) and 1 (non-optimal). Each score was summed into domain-specific composite scores and standardised according to the total sample. RESULTS: Participants included 262 VP/VLBW (52.7% males) and 230 term-born individuals (47.0% males). VP/VLBW adults had lower overall social relationship scores than term-born adults (ß = -.61, 95% CI -0.85, -0.37). Specifically, partner (ß = -.50, 95% CI-0.74, -0.27) and peer relationship scores (ß = -.55, 95% CI-0.78, -0.32) were lower than those of term-born adults, but scores did not differ for parent relationships. On average, partner (ß = .25, 95% CI 0.14, 0.35) and peer relationship scores increased (ß = .16, 95% CI 0.03, 0.29), while parent relationship scores decreased (ß = -.64, 95% CI-0.79, -0.49) from 26 to 34 years. These changes were similar for VP/VLBW and term-born individuals. CONCLUSIONS: Patterns of change for the improved partner and peer but worsening parental social relationship scores were common across VP/VLBW and term-born adults, but differences between the two groups persisted from 26 to 34 years.

Maternal mental disorders and neonatal outcomes: Danish population-based cohort study.

BACKGROUND: Previous studies have indicated associations between maternal mental disorders and adverse birth outcomes; however, these studies mainly focus on certain types of mental disorders, rather than the whole spectrum. AIMS: We aimed to conduct a broad study examining all maternal mental disorder types and adverse neonatal outcomes which is needed to provide a more complete understanding of the associations. METHOD: We included 1 132 757 liveborn singletons born between 1997 and 2015 in Denmark. We compared children of mothers with a past (>2 years prior to conception; n = 48 646), recent (2 years prior to conception and during pregnancy; n = 15 899) or persistent (both past and recent; n = 10 905) diagnosis of any mental disorder, with children of mothers with no mental disorder diagnosis before the index delivery (n = 1 057 307). We also considered different types of mental disorders. We calculated odds ratios and 95% CIs of low birthweight, preterm birth, small for gestational age, low Apgar score, Caesarean delivery and neonatal death. RESULTS: Odds ratios for children exposed to past, recent and persistent maternal mental disorders suggested an increased risk for almost all adverse neonatal outcomes. Estimates were highest for children in the 'persistent' group for all outcomes, with the exception of the association between persistent maternal mental disorders and neonatal death (odds ratio 0.96, 0.62-1.48). CONCLUSIONS: Our study provides evidence for increased risk of multiple adverse neonatal outcomes among children of mothers with mental disorders, highlighting the need for close monitoring and support for women with mental disorders.

Perinatal Outcomes of Women with Recurrent Pregnancy Loss Undergoing Frozen Embryo Transfer from the Society of Assisted Reproductive Technology Database.

OBJECTIVE: To assess whether infants born to women with a history of recurrent pregnancy loss (RPL) have an increased risk of adverse perinatal outcomes following frozen embryo transfer (FET) compared to women without a history of infertility or RPL. DESIGN: Retrospective cohort study utilizing the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) database between 2014 and 2020. SUBJECTS: Patients in the SART CORS database who underwent their first FET resulting in live birth either with a diagnosis of RPL (cases n=3,299) or without a history of RPL or infertility, the comparison population being tubal ligation (TL) only (n=1408). EXPOSURE: Recurrent pregnancy loss MAIN OUTCOME: Low birthweight (<2500g), additional outcomes included gestational age (continuous), birthweight (continuous), preterm delivery (< 37 weeks), mode of delivery, and neonatal death, defined as death prior to the completion of the 28th day of life. RESULTS: We observed no statistically significant difference in low birthweight, birthweight overall, mode of delivery or risk of neonatal death between patients with RPL compared to women with tubal ligation who underwent their first FET resulting in live birth. Patients with history of RPL compared to TL utilizing FET were more likely to have a later gestational age at delivery (p<0.001). Patients with RPL were also less likely to have a preterm delivery (imputed AOR 0.75 [0.64, 0.89]) than the TL patients. Furthermore, performing preimplantation genetic testing for aneuploidy (PGTA) in both patients with recurrent pregnancy loss or tubal ligation did not impact perinatal outcomes compared to patients who did not undergo PGTA. CONCLUSIONS: Patients with history of recurrent pregnancy loss do not have an increased risk of adverse perinatal outcomes when they undergo FET compared to patients without infertility or recurrent pregnancy loss. In addition, performing IVF/PGTA in patients with RPL does not adversely impact birth outcomes of their infants.

Association between neonatal mortality and births not weighed among 400 thousand institutional deliveries in 32 low- and middle-income countries.

BACKGROUND: Low birthweight (LBW) children have a higher risk of neonatal mortality. All institutional deliveries, therefore, should be weighed to determine appropriate care. Mortality risk for newborns who are not weighed at birth (NWB) is unknown. METHODS: This paper used logit regression models to compare the odds of death for NWB neonates to that of other neonates using data on 401 712 institutional births collected in Demographic and Health Surveys from 32 low- and middle-income countries. RESULTS: In the pooled sample, 2.3% died in the neonatal period and 12% were NWB. NWB neonates had a high risk of mortality compared to normal birthweight children (Adjusted odds ratio [AOR] 5.8, 95% CI: 5.3, 6.5). The mortality risk associated with NWB was higher than for LBW. The neonatal mortality risk associated with NWB varied across countries from AOR of 2.1 (95% CI: 1.22, 3.8) in Afghanistan to 94 (95% CI: 22, 215) in Gabon. In the pooled sample, the 12% of children who were NWB accounted for 37% of all neonatal deaths. CONCLUSIONS: The association between NWB and neonatal mortality may suggest a need to focus on the quality of institutions related to newborn care. However, further studies are needed to determine causality. A health emergency or death may also cause NWB.

A randomized-controlled trial of parent-administered interventions to improve short-term motor outcomes in hospitalized very low birthweight infants.

BACKGROUND: Premature infants are at increased risk for cerebral palsy (CP). Early interventions with a motor focus and administered by parents may improve motor outcomes. AIMS: Secondary study evaluating the short-term motor outcomes and risk for CP in very low birthweight (VLBW) infants randomized to multimodal interventions with a motor focus provided by parents versus usual care. STUDY DESIGN: Randomized controlled trial (intervention vs. usual care (control group)). SUBJECTS: Infants (<32 weeks' gestational age (GA) and/or <1500 grams birthweight) born between March 2019 and October 2020. OUTCOME MEASURES: Short-term motor outcomes and risk for CP was evaluated using the Hammersmith Infant Neurological Evaluation (HINE, primary motor outcome), the General Movement Assessment (GMA) and the Test of Infant Motor Performance (TIMP) at 3 months' postmenstrual age (PMA). RESULTS: 70 participants were enrolled (GA 28.3±2.7 weeks, birthweight 1139.2±376.6 grams, 64.3% male). The in-person follow-up rate was 73%, lower than expected, in part due to COVID-19 restrictions, resulting in 25 infants (intervention) and 26 infants (control) with outcome data available for analysis. There was not a significant difference in the HINE, GMA or TIMP at 3 months' PMA between groups. CONCLUSION: Multimodal interventions with a motor focus and provided by parents need further investigation to determine if they can improve short-term motor outcomes in VLBW infants. These interventions are evidence-based and the evaluation of broader implementation into routine care is also needed.

Radiographic scores as a predictor of oxygenation index in very low-birthweight infants.

BACKGROUND: Very low birthweight infants (VLBWIs) often undergo chest radiographic examinations without standardization or objectivity. This study aimed to assess the association of two radiographic scores, the Brixia and radiographic assessment of lung edema (RALE), with oxygenation index (OI) in ventilated VLBWIs and to determine the optimal cutoff values to predict hypoxic respiratory severity. METHODS: VLBWIs who received invasive respiratory support with arterial lines between January 2010 and October 2023 were enrolled in this study (n = 144). The correlation between the Brixia or RALE scores and OI was investigated. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff points of the two radiographic scores for predicting OI values (OI ≥5, ≥10, and ≥15). RESULTS: The enrolled infants had a median gestational age of 27 weeks (interquartile range [IQR], 25-28 weeks) and a median birthweight of 855 g (IQR, 684-1003 g). Radiographic scoring methods correlated with the OI (Brixia score: r = 0.79, p < 0.001; RALE score: r = 0.72, p < 0.001). The optimal cutoff points for predicting OI values were as follows: Brixia score: OI ≥5, 10; OI ≥10, 13; OI ≥15, 15; RALE score: OI ≥5, 22; OI ≥10, 31; and OI ≥15, 40. CONCLUSIONS: Brixia and RALE scores are useful predictive markers of the oxygenation status in intubated VLBWIs with stable hemodynamics. These scores are easy to use and promising tools for clinicians to identify patients with a higher risk of hypoxic respiratory failure.

Disease burden comparison and associated risk factors of early- and late-onset neonatal sepsis in China and the USA, 1990-2019.

BACKGROUND: The morbidity and mortality rates of neonatal sepsis are high, with significant differences in risk factors and disease burden observed between developing and developed countries. OBJECTIVE: To provide evidence to support recommendations on improving public health policies using a comparative systematic analysis of the disease burden. METHODS: Using data from the Global Burden of Disease Study 2019, the prevalence and incidence of early- and late-onset neonatal sepsis and the disability-adjusted life years (DALYs) due to both countries in both China and the United States of America (USA) were assessed. Furthermore, the DALYs and summary exposure values for the primary risk factors (short gestation and low birthweight) were analysed. Joinpoint regression models were used to analyse temporal trends in epidemiological indicators of neonatal sepsis. RESULTS: Between 1990 and 2019, the incidence and prevalence of neonatal sepsis demonstrated a significant upwards trend in China, whereas both were largely stable in the USA. A decreasing trend in the DALYs due to neonatal sepsis caused by short gestation and low birthweight in both sexes was observed in both countries, whereas a fluctuating increasing trend in years lived with disability was observed in China. CONCLUSIONS: The aim of the Chinese public health policy should be to control risk factors, learning from the advanced health policy planning and perinatal management experiences of developed countries.

Main findings Disability-adjusted life years (DALYs) attributed to short gestation and low birth-weight for neonatal sepsis have been decreasing in both China and the USA; years lived with disability (YLDs) and summary exposure values (SEVs) have been increasing in China.Added knowledge This study provides new knowledge about the disease burden of neonatal sepsis attributable to short gestation and low birthweight and suggests possible interventions.Global health impact for policy and action Public health policies in developing countries need to focus on moderating risk factors, learning from the advanced health policy planning and perinatal management experiences of developed countries, and improving neonatal follow-up and rehabilitation interventions.

A swallowing and breastfeeding intervention programme for small and sick neonates embedded in kangaroo mother care.

Available evidence of oral sensorimotor interventions for small neonates is not strong. Evidence of interventions for sick term neonates is largely lacking. Studies are limited by risk of bias and inconsistency. Evidence of interventions relying on a single stimulation technique only appears to be low to very low. Ongoing research is required.Contribution: We describe a five-component neonatal swallowing and breastfeeding intervention programme embedded in the practice of kangaroo mother care (KMC). Drawing on oropharyngeal physiology, neonatology, neurodevelopmental care, breastfeeding- and KMC science, the programme is the product of collaboration between a speech-language therapist and a medical doctor, and their team. Its implementation is dependent on coaching mothers and the neonatal care team. Researchers are invited to determine outcomes of the programme.

Adverse pregnancy outcomes in maternal malarial infection: A systematic review and meta-analysis.

Background: Malaria in pregnancy is a critical public health issue that can lead to severe adverse outcomes for both mother and fetus. This systematic review and meta-analysis evaluated the prevalence of adverse birth outcomes in malaria-infected pregnancies and examines their association with the condition. Method: We searched databases up to January 30, 2024, for observational studies on pregnant women with malaria. Data were analyzed using a random-effects model to calculate pooled prevalence rates and risk ratios (RRs) for adverse outcomes, with statistical support from R software version 4.3. Results: Thirty-one studies were included, showing high prevalence of low birth weight (LBW; 17.4 %), preterm birth (17.9 %), and small for gestational age (SGA; 16.1 %) in malaria-affected pregnancies. Infected mothers were significantly more likely to have LBW infants (RR = 1.755), preterm births (RR = 1.484), and SGA infants (RR = 1.554). The risk of stillbirth was not significantly increased (RR = 1.238). Conclusion: Malaria in pregnancy significantly elevates the risk of LBW, preterm birth, and SGA, underscoring the need for effective malaria prevention and treatment strategies in endemic regions. Future research should aim to refine and implement these strategies to enhance maternal and neonatal health outcomes.

Glucose disturbances in very low-birthweight infants-Results from the prospective LIGHT study.

AIM: To describe glucose homeostasis disturbances (dysglycaemia) in very low-birthweight infants (<1500 g) during the admission period and explore associated risk factors. METHODS: The LIGHT (very low-birthweight infants - glucose and hormonal profile over time) study was a prospective observational cohort study that included 49 very low-birthweight infants admitted to the tertiary neonatal intensive care unit in Umeå, Sweden, during 2016-2019. All glucose concentrations (n = 3515) sampled during the admission period were registered. RESULTS: Hyperglycaemia >10 mmol/L and hypoglycaemia <2.6 mmol/L were registered in 63% and 55% of the infants, respectively. Onset of dysglycaemia occurred almost exclusively in the first postnatal week. Hyperglycaemia followed 15% of corticosteroid doses given; all were preceded by pre-existing hyperglycaemia. Pre-existing hyperglycaemia was found in 66.7% of hyperglycaemic infants who received inotrope treatment. Upon commencement, 72.5% of antimicrobial treatments given were neither preceded nor followed by hyperglycaemia. CONCLUSION: Dysglycaemia was common in very low-birthweight infants. Daily means of glucose concentrations seemed to follow a postmenstrual age-dependent pattern, decreasing towards term age suggesting a postmenstrual age-dependent developmental mechanism. The primary mechanism causing hyperglycaemia was independent of sepsis, and corticosteroid and inotrope treatments. No hypoglycaemia was registered during ongoing insulin treatment.

Hypertension subtypes and adverse maternal and perinatal outcomes - a retrospective population-based cohort study.

BACKGROUND: This study aims to examine risk of adverse pregnancy outcomes and mothers' characteristics in patients with chronic hypertension, gestational hypertension and preeclampsia. METHODS: The study included all births born from women aged 15-45 years, in Lleida, Spain from 2012 to 2018. Pregnancy outcomes were retrieved by regional administrative databases. Logistic regression analysis was used to calculate adjusted odds ratios (OR) (OR 95% CI) for maternal characteristics or neonatal outcomes. RESULTS: Among 17,177 pregnant women, different types of hypertension present varying risks for both the mother and fetus. There is an increased risk of cesarean section in patients with preeclampsia (OR 2.04, 95% CI: 1.43-2.88). For the newborn, a higher risk of preterm birth is associated with maternal chronic hypertension (OR 3.09, 95% CI: 1.91-4.83) and preeclampsia (OR 5.07, 95% CI: 3.28-7.65). Additionally, there is a higher risk of low birth weight in cases of maternal chronic hypertension (OR 3.2, 95% CI: 2.04-4.88), preeclampsia (OR 5.07, 95% CI: 3.34-7.52), and gestational hypertension (OR 2.72, 95% CI: 1.49-4.68). Furthermore, only newborns of patients with preeclampsia had a higher risk of an Apgar score lower than 7 in the first minute (OR 2.95, 95% CI: 1.45-5.38). CONCLUSIONS: In the study population adjusted for body weight, the different types of hypertension represent different risks in the mother and foetus. These complications were mostly associated with preeclampsia.

Maternal ozone exposure lowers infant's birthweight: A nationwide cohort of over 4 million livebirths in Iran.

BACKGROUND: Nationwide evidence linking maternal ozone exposure with fetal growth restriction (FGR) was extensively scarce, especially in the Middle East with dry climate and distinct religious culture. METHODS: We carried out a national retrospective birth cohort study using registry-based records from 749 hospitals across 31 provinces in Iran from 2013 to 2018. Monthly concentrations of maximum daily average 8-hour (MDA8) ozone at 0.125° × 0.125° resolution were extracted from well-validated spatiotemporal grid dataset. Linear and logistic regression models were employed to evaluate associations of maternal MDA8 ozone exposure with birthweight outcomes. Assuming causality, the comparative risk assessment framework was utilized to estimate the burden of low birthweight (LBW), small for gestational age (SGA), and birthweight loss per livebirth (BLL) attributable to ambient ozone pollution. RESULTS: Of 4030383 livebirths included in the study, 264304 (6.6%) were LBW and 484405 (12.0%) were SGA. Each 10-ppb increase in MDA8 ozone exposure was associated with an odds ratio of 1.123 (95% confidence interval [CI]: 1.104 to 1.142) for LBW and 1.210 (95% CI: 1.197 to 1.223) for SGA, and a 30.5-g (95% CI: 29.0 to 32.0) reduction in birthweight. We observed approximately linear exposure-response relationships of maternal MDA8 ozone exposure with LBW (Pnonlinear= 0.786), SGA (Pnonlinear= 0.156), and birthweight reduction (Pnonlinear= 0.104). Under the premise of causal association, we estimated 6.6% (95% CI: 5.7 to 7.5) of LBW, 10.1% (95% CI: 9.6 to 10.6) of SGA, and 18.8 g (95% CI: 17.9 to 19.7) of BLL could be attributable to maternal ozone exposure in Iran. Considerably greater risk and burden of ozone-related FGR were observed among younger, less-educated, and rural-dwelling mothers. CONCLUSIONS: Our study provided compelling evidence that maternal ozone exposure was associated with heightened FGR risk and burden, particularly among socioeconomically disadvantaged mothers. These findings underscored the urgent need for government to incorporate socioeconomic factors into future ozone-related health policies, not only to mitigate pollution, but also minimize inequality.

Impact of the Choice of Diagnostic Criteria and Growth Reference on the Prevalence of Extrauterine Growth Restriction in Extremely-Low-Birthweight Infants.

BACKGROUND AND OBJECTIVES: Variable diagnostic criteria and growth charts have been used for extrauterine growth restriction (EUGR). The objective was to assess the prevalence and concordance of EUGR in extremely-low-birthweight (ELBW) infants with the most frequent diagnostic criteria and growth charts. MATERIALS AND METHODS: An observational, retrospective and multicenter study was conducted from 2011 to 2020 including ELBW infants from the Spanish SEN1500 Network. EUGR prevalence was calculated at discharge using different definitions: cross-sectional (anthropometry less than the 10th centile), longitudinal (decrease of more than 1 SD from birth to discharge), "true" cross-sectional and "true" longitudinal (using the criteria previously described, excluding infants small for gestational age at birth). Concordance among Fenton, Olsen and INTERGROWTH-21st was assessed with Fleiss' Kappa coefficient. RESULTS: The prevalence of EUGR was variable with the different definitions and growth references studied in the 7914 ELBW infants included. Overall, it was higher with Fenton for all the EUGR criteria studied by weight and length. The agreement among growth charts was substantial (κ > 0.6) for all the definitions except for longitudinal EUGR by weight (moderate, κ = 0.578). CONCLUSIONS: The prevalence of EUGR was variable in our cohort with the different diagnostic criteria and growth charts. The agreement among charts was good for all the definitions of EUGR except longitudinal EUGR by weight.

Transfer of Respiratory Syncytial Virus Prefusion F Protein Antibody in Low Birthweight Infants.

Background: Respiratory syncytial virus (RSV)-associated lower respiratory tract infection contributes significantly to morbidity/mortality worldwide in low birthweight (LBW) infants (<2500 g). Studies have demonstrated decreased maternal immunoglobulin G (IgG) transfer of various antibodies to LBW infants. We aimed to evaluate naturally acquired RSV anti-prefusion F protein (anti-preF) antibody transfer in pregnancies with LBW versus normal birthweight (NBW) infants. Methods: In this cohort study conducted among pregnant individuals and their infants, we tested paired maternal and singleton infant cord samples for RSV anti-preF IgG via an electrochemiluminescence immunoassay, using linear regression to evaluate associations between LBW and anti-preF IgG. Covariates included seasonality, insurance, small-for-gestational-age birthweight, and gestational age at delivery. Results: We tested maternal/cord RSV anti-preF IgG from 54 and 110 pregnancies with LBW and NBW infants, respectively. Of LBW infants, 22 (40.7%) were born both preterm and with small-for-gestational-age birthweight. The median (interquartile range) gestational age at delivery and birthweight were 34.0 (31.7-37.1) weeks and 1902 (1393-2276) g for LBW infants versus 39.1 (38.3-39.9) weeks and 3323 (3109-3565) g for NBW infants (both P < .001). In unadjusted comparisons, preterm infants had significantly lower cord anti-preF IgG levels and cord-maternal IgG ratios compared with full-term infants, while LBW infants had significantly lower cord-maternal IgG ratios than NBW infants (all P < .01). After adjustment for covariates, there was no difference in cord-maternal IgG ratios (ß =-0.29 [95% confidence interval, -.63 to .05]) between LBW and NBW infants. Conclusions: We documented robust transfer of maternal RSV anti-preF IgG in pregnancies with both LBW and NBW infants. Further studies are needed to assess immune protection in at-risk infants.

PeRinatal, neOnatal, and Maternal OuTcomEs with azithromycin prophylaxis in pregnancy and labour (PROMOTE-PROPHYLAXIS): systematic review and meta-analysis.

Background: Initial randomised controlled trials (RCTs) showed that prophylactic azithromycin in pregnant women improved maternal and neonatal outcomes; however, the recent evidence did not show any benefit to neonatal survival. There is conflicting evidence over the role of azithromycin prophylaxis in antenatal and intrapartum periods. We explored whether azithromycin prophylaxis in pregnant women improves maternal and neonatal outcomes. Methods: For this systematic review and meta-analysis registered on PROSPERO [CRD42023411093], we searched seven databases (PubMed, Scopus, Embase, Cochrane Library, EBSCOHost, ProQuest, and Web of Science) and clinical trial registries until 04/23/2024, for RCTs evaluating antenatal/intrapartum azithromycin prophylaxis against placebo/routine care in pregnant women. The primary outcome was neonatal mortality. Intrapartum and antenatal administration were assessed separately. We used random-effects meta-analysis. The risk of bias was assessed using the Cochrane RoB 2 tool. The GRADE approach was used to evaluate the certainty of the evidence. Findings: Screening 2161 records retrieved 20 RCTs (56,381 participants). Intrapartum azithromycin may make little or no difference to neonatal mortality [5 RCTs, 44,436 participants; Risk Ratio (RR): 1.02, 95% CI 0.86-1.20, I 2  = 0%, very low certainty], and maternal mortality [3 RCTs, 44,131 participants, RR: 1.26, 0.65-2.42, I 2  = 0%, low certainty]. Similarly, antenatal azithromycin may have little or no effect on neonatal mortality [3 RCTs; 5304 participants; RR: 0.74, 0.35-1.56, I 2  = 43%, very-low certainty] and maternal mortality [3 RCTs; 8167 participants RR: 1.62, 0.67-3.91, I 2  = 0%, low certainty]. There is no data on long-term adverse outcomes and antimicrobial resistance. Interpretation: Low to very low certainty evidence suggests that intrapartum or antenatal azithromycin prophylaxis in pregnant women might not reduce maternal or neonatal mortality. Funding: None.

Extrauterine growth restriction in very-low-birthweight infants: prevalence and concordance according to Fenton, Olsen, and INTERGROWTH-21st growth charts in a multicenter Spanish cohort.

Multiple criteria and growth references have been proposed for extrauterine growth restriction (EUGR). We hypothesized that these may impact the diagnosis of EUGR. The objective was to evaluate the prevalence of EUGR with its different definitions and the concordance according to Fenton, Olsen, and INTERGROWTH-21st in very-low-birthweight (VLBW) infants. This is an observational, retrospective, and multicenter study including VLBW infants from the Spanish SEN1500 Network from 2011 to 2020. Patients with major congenital anomalies, embryopathies, and gestational age less than 24 weeks were excluded. EUGR prevalence was calculated at discharge with cross-sectional, longitudinal, "true" cross-sectional, and "true" longitudinal definitions. Concordance was assessed with Fleiss' kappa coefficient. 23582 VLBW infants from 77 NICUs were included. In total, 50.4% were men with a median of gestational age of 29 (4) weeks. The prevalence of EUGR (cross-sectional, longitudinal, and "true") was variable for weight, length, and head circumference. Overall, the prevalence was higher with Fenton and lower with Olsen (cross-sectional and "true" cross-sectional) and INTERGROWTH-21st (longitudinal and "true" longitudinal). Agreement among the charts by weight was good only for cross-sectional EUGR and moderate for longitudinal, "true" cross-sectional, and "true" longitudinal. Concordance was good or very good for EUGR by length and head circumference.Conclusions: The prevalence of EUGR with the most commonly used definitions was variable in the cohort. Agreement among growth charts was moderate for all the definitions of EUGR by weight except cross-sectional and good or very good for length and head circumference. The choice of reference chart can impact the establishment of the diagnosis of EUGR. What is known: • EUGR has been defined in the literature and daily practice considering weight, length and head circumference with multiple criteria (cross-sectional, longitudinal, and "true" definition) • Different growth charts have been used for EUGR diagnosis What is new: • Prevalence of EUGR is variable depending on the definition and growth chart used in our cohort of VLBW infants • For the most frequently EUGR criteria used, traditionally considering weight, concordance among Fenton, Olsen and INTERGROWTH-21st growth charts is only moderate for all the definitions of EUGR by weight except cross-sectional definition. Concordance among the charts is good or very good for the different criteria of EUGR by head circumference and length.

Maternal inflammatory and microbial drivers of low birthweight in low- and middle-income countries.

BACKGROUND: Low birthweight (LBW) is when an infant is born too soon or too small, and it affects one in seven infants in low- and middle-income countries. LBW has a significant impact on short-term morbidity and mortality, and it impairs long-term health and human capital. Antenatal microbial and inflammatory exposure may contribute to LBW. METHODS: Ovid-Medline, Embase and Cochrane databases were searched for English-language articles evaluating inflammatory, microbial or infective causes of LBW, small-for-gestational age, intra-uterine growth restriction or prematurity. Inclusion criteria were human studies including published data; conference abstracts and grey literature were excluded. A narrative synthesis of the literature was conducted. RESULTS: Local infections may drive the underlying causes of LBW: for example, vaginitis and placental infection are associated with a greater risk of prematurity. Distal infection and inflammatory pathways are also associated with LBW, with an association between periodontitis and preterm delivery and environmental enteric dysfunction and reduced intra-uterine growth. Systemic maternal infections such as malaria and HIV are associated with LBW, even when infants are exposed to HIV but not infected. This latter association may be driven by chronic inflammation, co-infections and socio-economic confounders. Antimicrobial prophylaxis against other bacteria in pregnancy has shown minimal impact in most trials, though positive effects on birthweight have been found in some settings with a high infectious disease burden. CONCLUSION: Maternal inflammatory and infective processes underlie LBW, and provide treatable pathways for interventions. However, an improved understanding of the mechanisms and pathways underlying LBW is needed, given the impact of LBW on life-course.

Effect of low-cost kitchen with improved cookstove on birthweight of neonates in Shahjadpur, Bangladesh: a cluster-randomised controlled trial.

Background: Smoke from biomass fuels used for cooking in traditional cookstoves contains a variety of health-damaging pollutants. Inhalation of these pollutants by pregnant women has been linked to abnormal foetal development and adverse pregnancy outcomes, including low birthweight (LBW). There is a dearth of data on environmental interventions that have the potential to reduce exposure to biomass fuel during pregnancy and improve birth outcomes. International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) therefore, designed a low-cost kitchen with an improved cookstove and examined the impact of this intervention on the birthweight of neonates. Methods: icddr,b conducted a cluster-randomised controlled trial of a 'low-cost kitchen with improved cookstove' intervention among 1,267 pregnant women who used traditional cookstoves in a rural sub-district of Bangladesh. All participants were enrolled during the first trimester of pregnancy among 104 randomly selected clusters after obtaining informed consent. The model kitchens were installed in 628 participants' households of the intervention group, and 639 participants continued to use traditional cookstoves as the control group. The primary outcome was the proportion of LBW neonates between the intervention and control groups. The study also examined if the intervention would reduce CO exposure, measured by the differences in maternal blood carbon monoxide saturation (SpCO) levels and prevalence of LBW in neonates. We performed a generalized structural equation model for jointly assessing the simultaneous relationships of biomass fuel exposure to LBW of neonates and the relationships of LBW of neonates to maternal blood SpCO level. This trial was registered with ClinicalTrials.gov (NCT02923882). Findings: We found that in the intervention group using 'low-cost kitchen with improved cookstove', the risk of LBW reduced by 37% (adjusted risk ratio: 0.63, 95% CI [0.45, 0.89]). Between the second and third trimester, the mean maternal blood SpCO level was significantly reduced from 10.4% to 8.9% (p-value <0.01) in the intervention group but remained unchanged in the control group (11.6% and 11.5%). Of the total effects of the intervention on the risk of LBW, 48.3% was mediated through maternal blood SpCO level. Interpretation: The risk of LBW among rural neonates was reduced in the intervention group using 'low-cost kitchen with improved cookstove', which may be attributed to the reduction in maternal blood SpCO level. Additional research is needed to identify other mechanisms through which biomass fuel exposure might lead to adverse pregnancy outcomes. Funding: Grand Challenges Canada: Rising Stars in Global Health Programme.