UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Low to very low certainty evidence suggests that intrapartum or antenatal azithromycin prophylaxis in pregnant women might not reduce maternal or neonatal mortality.
UNASSIGNED: None.

UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Grand Challenges Canada: Rising Stars in Global Health Programme.

Low birthweight is associated with poor health, developmental, and social outcomes throughout the lifespan. Exposure to adverse childhood experiences (ACEs) is also associated with negative mental and physical health outcomes in adulthood. The aims of this study were to explore the relationship between low birthweight (LBW), exposure to ACES, and subsequent utilization of mental health service. Data analysis was conducted using a subset of data from children ages 6-17 years from the National Survey of Children\'s Health (NSCH) for 2018-2019 (n = 40,656). Welch ANOVA, Pearson\'s chi-square, and logistic regression investigated the relationship between LBW, ACEs, and mental health. LBW children in this sample had higher exposure to ACEs when compared to not low birthweight (NBW) children. LBW children also had a higher reported incidence of identified mental health (MH) issues. There was no significant association between birthweight and unmet MH service needs. LBW children with an ACE score or two or more were more likely to have an unidentified MH issue and/or an unmet MH service need. The results demonstrate LBW children experience higher levels of adversity. Children with ACE scores of two or more and those with unidentified MH issues have a higher likelihood of unmet MH needs. Professionals working in the health, education, and social service sectors can use this information to raise awareness of the increased vulnerability and more effectively meet the mental health needs of LBW children.

Intrauterine growth-restricted (IUGR) fetuses exhibit systemic inflammation that contributes to programmed deficits in myoblast function and muscle growth. Thus, we sought to determine if targeting fetal inflammation improves muscle growth outcomes. Heat stress-induced IUGR fetal lambs were infused with eicosapentaenoic acid (IUGR+EPA; n = 9) or saline (IUGR; n = 8) for 5 days during late gestation and compared to saline-infused controls (n = 11). Circulating eicosapentaenoic acid was 42% less (p < 0.05) for IUGR fetuses but was recovered in IUGR+EPA fetuses. The infusion did not improve placental function or fetal O2 but resolved the 67% greater (p < 0.05) circulating TNFα observed in IUGR fetuses. This improved myoblast function and muscle growth, as the 23% reduction (p < 0.05) in the ex vivo differentiation of IUGR myoblasts was resolved in IUGR+EPA myoblasts. Semitendinosus, longissimus dorsi, and flexor digitorum superficialis muscles were 24-39% lighter (p < 0.05) for IUGR but not for IUGR+EPA fetuses. Elevated (p < 0.05) IL6R and reduced (p < 0.05) β2 adrenoceptor content in IUGR muscle indicated enhanced inflammatory sensitivity and diminished β2 adrenergic sensitivity. Although IL6R remained elevated, β2 adrenoceptor deficits were resolved in IUGR+EPA muscle, demonstrating a unique underlying mechanism for muscle dysregulation. These findings show that fetal inflammation contributes to IUGR muscle growth deficits and thus may be an effective target for intervention.

BACKGROUND: The risk of recurrent adverse birth outcomes has been reported worldwide, but there are limited estimates of these risks by social subgroups such as race and ethnicity in the United States. We assessed racial and ethnic disparities in the risk of recurrent adverse birth outcomes, including preterm birth, low birthweight, fetal growth restriction, small for gestational age, stillbirth, and neonatal mortality in the U.S.
METHODS: We searched MEDLINE, CINAHL Complete, Web of Science, and Scopus from the date of inception to April 5, 2022. We identified 3,540 articles for a title and abstract review, of which 80 were selected for full-text review. Studies were included if they focused on the recurrence of any of the six outcomes listed in the objectives. Study quality was assessed using the NIH Study Quality Assessment Tool. Heterogeneity across studies was too large for meta-analysis, but race and ethnicity-stratified estimates and tests for homogeneity results were reported.
RESULTS: Six studies on recurrent preterm birth and small for gestational age were included. Pooled comparisons showed a higher risk of recurrent preterm birth and small for gestational age for all women. Stratified race comparisons showed a higher but heterogeneous risk of recurrence of preterm birth across Black and White women. Relative risks of recurrent preterm birth ranged from 2.02 [1.94, 2.11] to 2.86 [2.40, 3.39] for Black women and from 3.23 [3.07, 3.39] to 3.92 [3.35, 4.59] for White women. The evidence was weak for race and ethnicity stratification for Hispanic and Asian women for both outcomes.
CONCLUSIONS: Disparities exist in the recurrence of preterm birth, and race/ethnicity-concordant comparisons suggest race is an effect modifier for recurrent preterm birth for Black and White women. Due to the small number of studies, no conclusions could be made for small for gestational age or Hispanic and Asian groups. The results pose new research areas to better understand race-based differences in recurrent adverse birth outcomes.

UNASSIGNED: The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP), the dapivirine vaginal ring, and long-acting intramuscular injectable cabotegravir (CAB-LA) for HIV prevention in populations at substantial risk of HIV infection. Pregnancy is a period of elevated risk of maternal HIV infection and transmission to the infant. This systematic review and meta-analysis assessed the risk of adverse perinatal outcomes among HIV-negative pregnant women with exposure to any PrEP modality.
UNASSIGNED: We conducted a systematic review by searching Medline, EMBASE, CINAHL, Global Health, the Cochrane Library, WHO ICTR, ISRCTN, PACTR, and ClinicalTrials.gov for studies published between 1 January 2000 and 29 August 2023. We included studies reporting on the association of antenatal exposure to any PrEP modality with 13 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, spontaneous very PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA, miscarriage, stillbirth, or neonatal death (NND). Quality assessments of included studies were performed. Fixed-effect meta-analyses were conducted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). The protocol is registered with PROSPERO, CRD42022339825.
UNASSIGNED: Of 18,598 citations identified, 13 studies (eight randomised controlled trials (RCTs) and five cohort studies), assessing 8712 pregnant women in Africa, were included. Oral PrEP, compared to no PrEP, was not associated with PTB in meta-analyses of six RCTs (OR 0.73, 95% CI 0.43-1.26; I2 = 0.0%) or five unadjusted cohort studies (OR 0.84, 95% CI 0.69-1.03; I2 = 0.0%), but was associated with a reduced risk of PTB in three adjusted cohort studies (aOR 0.67; 95% CI 0.52-0.88, I2 = 0.0%). There was no association of oral PrEP with LBW, vLBW, SGA, or NND, compared to no PrEP. There was no association with PTB when oral TDF/emtricitabine (FTC) PrEP, oral TDF PrEP, and tenofovir vaginal gel were compared to each other. There was no association of the dapivirine vaginal ring with PTB or NND, compared to placebo or oral TDF/FTC PrEP. We found no data on CAB-LA.
UNASSIGNED: We found no evidence of adverse perinatal outcomes associated with PrEP exposure during pregnancy. Our findings support the WHO recommendation to provide oral PrEP to women of reproductive age and pregnant women. More data is needed to assess the safety of all PrEP modalities in pregnancy.
UNASSIGNED: None.

Background: Wasting and underweight in infancy is an increasingly recognised problem but consensus on optimum assessment is lacking. In particular, there is uncertainty on how to interpret anthropometry among low birth weight (LBW) infants who may be growing normally. This research aimed to determine growth of infants from birth to two months (around age of vaccination) and the mortality risk of underweight LBW infants compared to normal birth weight (NBW) infants at two and six months age. Methods: A secondary analysis of a birth cohort of 1103 infants in Burkina Faso was conducted. Anthropometry was performed monthly from 0 to 12 months. We assessed associations with mortality using Cox proportional hazards models and assessed discriminatory values using area under receiver operating characteristics curves. Results: Eighty-six (7.8%) children died by age one year, 26/86 (30%) and 51/86 (59%) within two and six months, respectively. At age two months, weight gain since birth did not better discriminate mortality risk than current weight-for-age (P=0.72) or mid-upper arm circumference (P=0.21). In total, 227 (21%) LBW infants had increased risk of mortality: adjusted hazards ratio (aHR) 3.30 (95%CI 2.09 to 4.90). Among infants who were underweight at two and six months, LBW infants (64% and 49%, respectively) were not at reduced risk of death compared to NBW infants (aHR 2.63 (95%CI 0.76 to 9.15) and 2.43 (95%CI 0.74 to 7.98), respectively). Conclusion: Assessing weight gain since birth does not offer advantages over immediate anthropometry for discriminating mortality risk. LBW infants who are later identified as underweight require care to help prevent mortality.

BACKGROUND: Preterm birth (birth before 37 completed weeks of pregnancy) is the leading cause of neonatal and child under-five mortality globally, both of which are highest regionally in sub-Saharan Africa. The skin barrier plays a critical role in neonatal health and increasing evidence supports the use of topical emollient therapy to promote postnatal growth and reduce hospital-acquired infections in preterm infants. The World Health Organization (WHO) currently recommends emollient therapy in preterm or low birthweight infants globally but calls for further research on impacts of emollient use, especially in Africa. Little is known about postnatal skincare practices and the tradition of oil massage across sub-Saharan Africa. Further documentation is necessary to understand the context for future emollient intervention trials.
METHODS: 61 semi-structured interviews with mothers who just delivered preterm or term infants and 4 focus group discussions (32 participants) with physician and nurse providers of newborn care were conducted at Sally Mugabe Central Hospital (SMCH), in Harare, Zimbabwe. SMCH is the principal public-sector tertiary care hospital for newborn infants in the northern part of the country. Mothers and healthcare professionals were questioned about newborn care at the hospital, current neonatal skincare and bathing practices, and the community\'s receptivity to a future emollient therapy clinical trial.
RESULTS: Postnatal skincare is centrally important to Zimbabwean communities and petroleum jelly application is nearly universal. The use of cooking oil and other natural oils on infants is also part of traditional customs. The primary needs and desires of mothers who have just given birth to preterm infants are having greater agency in their children\'s care and financial support in purchasing prescribed medications while at the hospital. Community receptivity to emollient therapy as a cost-effective treatment is high, particularly if mothers are trained to assist with the intervention.
CONCLUSIONS: Emollient therapy will likely be well-received by communities in and around Harare because of its accordance with current skincare practices and perceptions; however, cultural norms and the experiences of new mothers who have given birth at a facility highlight challenges and considerations for future clinical trial execution.
BACKGROUND: Clinicaltrials.gov NCT05461404.

UNASSIGNED: Integrase strand transfer inhibitor (INSTI) dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended by World Health Organisation as preferred first-line regimen in pregnant women living with human immunodeficiency virus (HIV) (WLHIV). Non-nucleoside reverse transfer inhibitor (NNRTI)-based ART and protease inhibitor (PI)-based ART are designated as alternative regimens. The impact of different ART regimens on perinatal outcomes is uncertain. We aimed to assess the comparative risk of adverse perinatal outcomes in WLHIV receiving different classes of ART.
UNASSIGNED: A systematic literature review was conducted by searching PubMed, CINAHL, Global Health, and EMBASE for studies published between Jan 1, 1980, and July 14, 2023. We included studies reporting on the association of pregnant WLHIV receiving different classes of ART with 11 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Pairwise random-effects meta-analyses compared the risk of each adverse perinatal outcome among WLHIV receiving INSTI-ART, NNRTI-ART, PI-ART, and nucleoside reverse transfer inhibitor (NRTI)-based ART, and compared specific \"third drugs\" from different ART classes. Subgroup and sensitivity analyses were conducted based on country income status and study quality.
UNASSIGNED: Thirty cohort studies published in 2006-2022, including 222,312 pregnant women, met the eligibility criteria. Random-effects meta-analyses found no evidence that INSTI-ART is associated with adverse perinatal outcomes compared to NNRTI-ART and PI-ART. We found that PI-ART is associated with a significantly increased risk of SGA (RR 1.28, 95% confidence interval (95% CI) [1.09, 1.51], p = 0.003) and VSGA (RR 1.41, 95% CI [1.08, 1.83], p = 0.011), compared to NNRTI-ART. Specifically, lopinavir/ritonavir (LPV/r) was associated with an increased risk of SGA (RR 1.40, 95% CI [1.18, 1.65], p = 0.003) and VSGA (RR 1.84, 95% CI [1.37, 2.45], p = 0.002), compared to efavirenz, but not compared to nevirapine. We found no evidence that any class of ART or specific \"third drug\" was associated with an increased risk of PTB.
UNASSIGNED: Our findings support the recommendation of INSTI-ART as first-line ART regimen for use in pregnant WLHIV. However, the increased risks of SGA and VGSA associated with PI-ART, compared to NNRTI-ART, may impact choice of second- and third-line ART regimens in pregnancy.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021248987.

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