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.

Daily Eicosapentaenoic Acid Infusion in IUGR Fetal Lambs Reduced Systemic Inflammation, Increased Muscle ADRß2 Content, and Improved Myoblast Function and Muscle Growth.

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) ß2 adrenoceptor content in IUGR muscle indicated enhanced inflammatory sensitivity and diminished ß2 adrenergic sensitivity. Although IL6R remained elevated, ß2 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.

Racial and ethnic differences in the risk of recurrent preterm or small for gestational age births in the United States: a systematic review and stratified analysis.

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.

A novel scale for assessing the risk of low birthweight: Birthweight questionnaire.

BACKGROUND: The birthweight of a newborn is critical to their health, development, and well-being. Previous studies that used maternal characteristics to predict birthweight did not employ a harmonised scale to assess the risk of low birthweight (LBW). OBJECTIVE: The goal of this study was to develop a new instrument that uses items on a uniform scale to assess the risk of an LBW in a pregnant woman. METHODS: Item response theory was employed to evaluate a similar existing scale, and some weaknesses were identified. RESULTS: Based on the observed weaknesses of the existing scale, a new uniform scale was developed, which is a 3-point Likert scale consisting of seven items. CONCLUSION: The scale, termed birthweight questionnaire, is a valuable tool for collecting data that could assist in assessing the risk of an LBW at every stage of pregnancy.

Exploring the Relationship between Adverse Childhood Experiences (ACEs) and Mental Health in Low Birthweight Children.

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.

Linking weather and health outcomes: Examining the potential influences of weather factors and particulate matter pollution on adverse pregnancy outcomes in the Kavre district, Nepal.

INTRODUCTION: Adverse pregnancy outcomes (APOs) include stillbirth, preterm birth, and low birthweight (LBW). Studies exploring the impact of weather factors and air pollution on APOs are scarce in Nepal. We examined the impacts of prenatal exposure to temperature, precipitation, and air pollution (PM2.5) on APOs among women living in Kavre, Nepal. METHODS: We conducted a hospital and rural health centers-based historical cohort study that included health facility birth records (n = 1716) from the Nepali fiscal year 2017/18 through 2019/20. We linked health records to temperature, precipitation, and PM2.5 data for Kavre for the six months preceding each birth. A random intercept model was used to analyze birthweight, while a composite APO variable, was analyzed using multivariable logistic regression in relation to environmental exposures. RESULTS: The proportion of LBW (<2500 gm), preterm birth (babies born alive before 37 weeks of gestation), and stillbirth was 13%, 4.3%, and 1.5%, respectively, in this study. Overall, around 16% of the study participants had one or more APOs. Total precipitation (ß: 0.17, 95% CI 0.01 to 0.33, p = 0.03) had a positive effect on birthweight in the wetter season. Negative effects for mean maximum (ß: 33.37, 95% CI -56.68 to -10.06, p = 0.005), mean (ß: 32.35, 95% CI -54.44 to -10.27, p = 0.004), and mean minimum temperature (ß: 29.28, 95% CI -49.58 to -8.98, p = 0.005) on birthweight was also observed in the wetter season. CONCLUSION: A positive effect of temperature (mean maximum, mean, and mean minimum) and total precipitation on birthweight was found in the wetter season. This study emphasizes the need for future research using larger cohorts to elucidate these complex relationships in Nepal.

Social Determinants of Premature Birth.

Social determinants of health have received increasing attention in public health, leading to increased understanding of how social factors-individual and contextual-shape the health of the mother and infant. However, racial differences in birth outcomes persist, with incomplete explanation for the widening disparity. Here, we highlight the social determinants of preterm birth, with special attention to the social experiences among African American women, which are likely attributed to structural racism and discrimination throughout life.

Behavior and circadian glucocorticoids in prepubertal monozygotic twins with birthweight differences: A prospective longitudinal cohort study on twin-to-twin transfusion syndrome patients.

BACKGROUND/OBJECTIVE: Low birthweight may have adverse sequelae in later life. Therefore, we analyzed behavioral difficulties and salivary glucocorticoid profiles in monozygotic twins with intra-twin birthweight differences due to twin-to-twin transfusion syndrome (TTTS). METHODS: 46 monozygotic TTTS twin pairs with birthweight differences of <1SDS (concordant; n=29) and ≥1SDS (discordant; n=17) were recruited at a mean age of 6.9 years for a prospective longitudinal cohort study. For glucocorticoid analysis, saliva samples were collected (at 7 h, 13 h, 18 h and 21 h) and analyzed with liquid chromatography-tandem mass spectrometry. Parents completed the Strengths and Difficulties Questionnaire. RESULTS: From the parents' perspective, the formerly smaller twins had statistically higher scores regarding hyperactivity (mean 4.63 vs 3.48, p=0.003) and emotional problems (mean 2.67 vs 2.02, p=0.042). Less catch-up growth (Δintra-twin height SDS 4 years of age - Δintra-twin birth length SDS) of the smaller twins was associated with higher scores for hyperactivity (Adj. R²=0.261, p<0.001, ß=-1.88, F(1.44)=16.86, n=46, f²=0.35), while smaller birthweight (Adj. R²=0.135, p=0.007, ß=-0,87, F(1.44)=8.03, n=46, f²=0.16) and birth length (Adj. R²=0.085, p=0.028, ß=-0,78, F(1.44)=5.19, n=46, f²=0.09) were associated with higher scores for peer problems. Greater Δintra-twin for cortisol (7 h: rho=0.337, p=0.029; cumulative: rho=0.458; p=0.024) and cortisone (7 h: rho=0.329, p=0.029; 13 h: rho=0.436, p=0.005) correlated with a greater Δintra-twin for conduct problems. In the discordant group, circa 1 SDS in head circumference persisted from birth (mean SDS: smaller twin -1.18, larger twin -0.08, p<0.001) to present (mean SDS: smaller twin -1.16, larger twin -0.14, p<0.001). CONCLUSION: Higher cortisol and cortisone concentrations in smaller twins were associated with higher scores for conduct problems. Lower birthweight and absent catch-up growth affected the parents' perspective on the smaller twins' behavior. They saw those children as more hyperactive, with more peer problems and emotional problems. Thus, it seems important to introduce regular check-ups where behavioral difficulties can be assessed, and assistance and advice can be given to the families. Due to the persisting smaller head circumference in the smaller discordant twins, this should be measured regularly.

Actual electrolyte intake during the first week of life and morbidity in very-low-birthweight infants.

AIM: To describe sodium and potassium intake, their sources and plasma concentrations, and the association between intake and morbidity in very-low-birthweight (VLBW, <1500 g) infants during the first week of life. METHODS: This retrospective cohort study comprised 951 VLBW infants born at <32 weeks. Infants were divided into three groups according to gestational age: 23-26 (n = 275), 27-29 (n = 433) and 30-31 (n = 243) weeks. Data on fluid management and laboratory findings were acquired from an electronic patient information system. RESULTS: The median sodium intake was highest in the 23-26 week group, peaking at 6.4 mmol/kg/day. A significant proportion of sodium derived from intravascular flushes; it reached 27% on day 1 in the 23-26 week group. High cumulative sodium intake in the first postnatal week was associated with weight gain from birth to day 8 in the 23-26 week group. High intake of sodium associated with an increased risk of surgically ligated patent ductus arteriosus (PDA), bronchopulmonary dysplasia and intraventricular haemorrhage, whereas low intake of potassium associated with an increased risk of PDA. CONCLUSION: Sodium intake in the most premature infants exceeded recommendations during the first postnatal week. Saline flushes accounted for a significant proportion of the sodium load.

Growth patterns by birth size of preterm children born at 24-29 gestational weeks for the first 3 years.

BACKGROUND: Concerns are prevalent about preterm infant long-term growth regarding plotting low on growth charts at discharge, stunting, underweight, high body fat and subsequent cardiometabolic morbidities. OBJECTIVES: To examine (a) longitudinal growth patterns of extremely and very preterm infants to 3 years corrected age (CA) (outcome), categorised by their birthweight for gestational age: small, appropriate and large for gestational age (SGA, AGA and LGA, respectively) (exposure); and (b) the ability of growth faltering (<-2 z-scores) to predict suboptimal cognitive scores at 3 years CA. METHODS: Post-discharge head, length, weight and weight-4-length growth patterns of the PreM Growth cohort study infants born <30 weeks and < 1500 g, who had dietitian and multi-disciplinary support before and after discharge, were plotted against the World Health Organization growth standard. Infants with brain injuries, necrotising enterocolitis and bronchopulmonary dysplasia were excluded. RESULTS: Of the included 405 infants, the proportions of infants with anthropometric measures > - 2 z-scores improved with age. The highest proportions <-2 z-scores for length (24.2%) and weight (24.0%) were at 36 gestational weeks. The proportion with small heads was low by 0 months CA (1.8%). By 3 years CA, only a few children plotted lower than -2 z-scores for length, weight-4-length and weight (<6%). After zero months CA, high weight-4-length and body mass index > + 2 z-scores were rare (2.1% at 3 years CA). Those born SGA had higher proportions with shorter heights (16.7% vs. 5.2%) and lower weights (27.8% vs. 3.5%) at 3 years CA compared to those born AGA. The ability of growth faltering to predict cognitive scores was limited (AUROC 0.42, 95% CI 0.39, 0.45 to 0.52, 95% CI 0.41, 0.63). CONCLUSIONS: Although children born <30 weeks gestation without major neonatal morbidities plot low on growth charts at 36 weeks CA most catch up to growth chart curves by 3 years CA.

The immune phenotype of perinatal anxiety in an anxiety-focused behavioral intervention program in Pakistan.

BACKGROUND: Dysregulation of the immune system has been associated with psychiatric disorders and pregnancy-related complications, such as perinatal depression. However, the immune characteristics specific to perinatal anxiety remain poorly understood. In this study, our goal was to examine specific immune characteristics related to prenatal anxiety within the context of a randomized controlled trial designed to alleviate anxiety symptoms-the Happy Mother - Healthy Baby (HMHB) study in Rawalpindi, Pakistan. MATERIALS AND METHODS: Pregnant women (n = 117) were followed prospectively in the 1st, 2nd, and 3rd trimesters (T1, T2, T3) and at 6 weeks postpartum (PP6). Each visit included a blood draw and anxiety evaluation (as measured by the anxiety subscale of the Hospital Anxiety and Depression Scale - HADS -using a cutoff ≥ 8). We enrolled both healthy controls and participants with anxiety alone; those with concurrent depression were excluded. RESULTS: K-means cluster analysis revealed three anxiety clusters: Non-Anxiety, High and Consistent Anxiety, and Decreasing Anxiety. Principal components analysis revealed two distinct clusters of cytokine and chemokine activity. Women within the High and Consistent Anxiety group had significantly elevated chemokine activity across pregnancy (in trimester 1 (ß = 0.364, SE = 0.178, t = 2.040, p = 0.043), in trimester 2 (ß = 0.332, SE = 0.164, t = 2.020, p = 0.045), and trimester 3 (ß = 0.370, SE = 0.179, t = 2.070, p = 0.040) compared to Non-Anxiety group. Elevated chemokine activity was associated with low birthweight (LBW) and small for gestational age (SGA). CONCLUSION: Our findings reveal a unique pattern of immune dysregulation in pregnant women with anxiety in a Pakistani population and offer preliminary evidence that immune dysregulation associated with antenatal anxiety may be associated with birth outcomes. The dysregulation in this population is distinct from that in our other studies, indicating that population-level factors other than anxiety may play a substantial role in the differences found. (Clinicaltrials.gov # NCT04566861).

Association Between Periodontitis and Adverse Pregnancy Outcomes: Two-Sample Mendelian Randomisation Study.

AIM: This Mendelian randomisation (MR) study endeavoured to delineate the causal relationship between periodontitis and adverse pregnancy outcomes (APOs), encompassing low birthweight (LBW), pre-term birth (PTB), stillbirth, miscarriage, and gestational hypertension (GH). METHODS: Utilising genetic instruments for periodontitis (acute and chronic periodontitis) from the Genome-Wide Association Study (GWAS) database among individuals of European descent, this study explored the causal relationship with adverse pregnancy outcomes, and vice versa. The Inverse Variance Weighted (IVW) method was employed as the primary analytical approach to assess causality, with MR-Egger serving as a sensitivity analysis method. RESULTS: The primary analytical method employed in this study, IVW, did not reveal any impact of periodontitis (acute and chronic periodontitis) on PTB, stillbirth, miscarriage, and gestational hypertension, and vice versa. Heterogeneity testing using the MR-Egger method confirmed the null causal hypothesis, with odds ratios (OR) approximating 1, and P-values exceeding 0.05. Notably, the results from the IVW analysis (OR 1.410, CI 1.039-1.915, P-value 0.028) indicate statistically significant evidence supporting a causal relationship between chronic periodontitis and LBW. However, caution is advised in interpreting the causal relationship, considering the non-significant P-values obtained from other methods. CONCLUSION: Within the limitations of this MR study, the findings do not support the influence of periodontitis on LBW, PTB, stillbirth, miscarriage, and GH, nor vice versa.

A greater nurse and midwife density protects against infant mortality globally.

PURPOSE: As the largest profession within the health care workforce, nurses and midwives play a critical role in the health and wellness of families especially children and infants. This study suggests those countries with higher nurse and midwife densities (NMD) had lower infant mortality rates (IMR). DESIGN AND METHODS: With affluence, low birthweight and urbanization incorporated as potential confounders, this ecological study analyzed the correlations between NMD and IMR with scatterplots, Pearson r correlation, partial correlation and multiple linear regression models. Countries were also grouped for analysing and comparing their Pearson's coefficients. RESULTS: NMD inversely and significantly correlated to IMR worldwide. This relationship remained significant independent of the confounders, economic affluence, low birthweight and urbanization. Explaining 57.19% of IMR variance, high NMD was implicated in significantly reducing the IMR. PRACTICE IMPLICATIONS: Countries with high NMD had lower IMRs both worldwide and with special regard to developing countries. This may interest healthcare policymakers, especially those from developing countries, to consider the impacts of global nursing and midwifery staffing shortages. Nurses and midwives are the group of healthcare professionals who spend most with infants and their carers. This may be another alert for the health authorities to extend nurses and midwives' practice scope for promoting infant health.

Influence of an Early Human Milk Diet on the Duration of Parenteral Nutrition and Incidence of Late-Onset Sepsis in Very Low Birthweight (VLBW) Infants: A Systematic Review.

Introduction: Human milk is the preferred source of enteral nutrition for very low birthweight (VLBW) infants, and it possibly decreases dependence on parenteral nutrition (PN) and reduces incidence of late-onset sepsis (LOS). No systematic review to date has specifically addressed the value of early versus late introduction of human milk diet (HMD) on duration of PN and incidence of LOS among VLBW infants. Objective: To review the evidence for an early versus late introduction of HMD on duration of PN and incidence of LOS in VLBW infants. Method: Preferred reporting items for systematic reviews and meta-analysis-guided search of EMBASE and PubMed/Medline databases was conducted for this systematic review using phrases addressing population, intervention, comparator, and outcome framework to identify articles published over the past two decades without language restrictions. Full-text articles (both observational and randomized) that studied an early versus late initiation of HMD were included. Mean difference (MD) and relative risk (RR) with 95% confidence intervals (CIs) were calculated for PN and LOS. Quality of evidence was analyzed using UK National Service Framework and the risk-of-bias was assessed using Robvis®. Results: One randomized controlled trial (RCT) and two observational studies (two English and one Chinese) recruited 474 VLBW infants (455 analyzed). Among an intrauterine growth-restricted cohort enrolled in the RCT (n = 72), early HMD resulted in statistically significant reduction in PN dependence. However, no statistically significant difference was found in LOS. Two observational studies found similar reductions in PN duration and LOS incidence among the early HMD cohort. One observational study reported significant PN reduction; however, the incidence of LOS did not reach statistical significance in either case. Conclusion: An early HMD may reduce the duration of PN for a growth-restricted VLBW cohort. Observational studies suggesting reduced PN and LOS from early HMD endorse the need for bioactivity-focused human milk research. Variations in feeding guidelines among VLBW infants have the potential to influence neonatal outcomes significantly.

Perinatal outcomes associated with pre-exposure prophylaxis for HIV prevention during pregnancy: a systematic review and meta-analysis.

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: None.

Wide use of broad-spectrum antibiotics in very low birth weight infants with spontaneous focal intestinal perforation-is it really justified?

PURPOSE: Very low birth weight (VLBW) infants are at a risk of spontaneous focal intestinal perforation (FIP). Treatment includes supportive care, antibiotics, and drainage with/without surgery. Broad-spectrum antibiotic agents like carbapenems are applied frequently, although their use is not well-supported by the limited evidence of causal pathogens. We hypothesize that the use of carbapenems may not be necessary in VLBW infants with FIP. Our primary objective was to evaluate the antimicrobial use in VLBW infants with FIP in a cohort of the German Neonatal Network (GNN). The secondary objective was to characterize a subset in detail as a benchmark for future targets of stewardship. METHODS: Data on VLBW infants with FIP was collected prospectively within the GNN, a collaboration of 68 neonatal intensive care units (NICU). With regards to the primary objective, patient characteristics and antimicrobial treatment were extracted from the predefined GNN database. To address our secondary objective, an additional on-site assessment of laboratory and microbiological culture results were performed. RESULTS: In the GNN cohort, 613/21,646 enrolled infants (2.8%) developed FIP requiring surgery. They were frequently treated with carbapenems (500/613 (81.6%)) and vancomycin (497/613 (81.1%)). In a subset of 124 VLBW infants, 77 (72.6%) had proof of gram-positive bacteria in the abdominal cavity, coagulase-negative staphylococci (CoNS) predominantly. Despite the low prevalence of gram-negative bacteria (n = 6 (4.8%)), the combination of meropenem and vancomycin was prescribed most frequently (n = 96 (78.0%)). CONCLUSION: The use of carbapenems as broad-spectrum antimicrobials agents might not be justified in most VLBW infants with FIP. Knowledge on the development of the neonatal gut microbiota, local resistance patterns and individual microbiological findings should be taken into consideration when implementing antimicrobial stewardship programs (ASPs).

A quality improvement strategy to reduce unintended extubation in the very low birth weight infant: A case report.

BACKGROUND: Unintended extubations remain a common complication across neonatal intensive care units, with very low birthweight infants being the most vulnerable of them all. Ongoing efforts across different institutions exist with the goal of reducing the rate of unintended extubations to keep a median rate of <2 events per 100 ventilator days as defined by the Vermont Oxford Network. Our objective was to reduce unintended extubations in the very low birthweight infant in a large delivery hospital to ≤2/100 ventilator days. METHODS: A collaborative group was formed between two academic health institutions targeting training and implementation of the Children's National unintended extubation system, focusing on endotracheal tube securement methods and surveillance protocols. RESULTS: The unintended extubation rate decreased from 3.23 to 0.64 per 100 ventilator days. Changes were implemented from 2018-2020 with a sustained reduction in the unintended extubation rate of 1.54 per 100 ventilator days. Most events occurred between 12 : 00 pm -4 : 00 pm and the commonest cause was spontaneous (25%) followed by dislodgment during repositioning (19%). CONCLUSION: Very low birth weight infants present a challenge to endotracheal tube maintenance due to their developmental and anatomical changes during their neonatal intensive care unit stay. Successful reduction of unintended extubations in the very low birthweight infant can be achieved by adaptation of successful protocols for older infants.

Relationships of Severity of Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes and Poor Respiratory Function at 7-8 Years of Age.

OBJECTIVE: To clarify the relationships of 3 definitions of severity of bronchopulmonary dysplasia (BPD) with adverse neurodevelopmental and respiratory outcomes at early school-age. STUDY DESIGN: Participants comprised 218 consecutive survivors to 7-8 years of age born either <28 weeks' gestation or weighing <1000 g in Victoria, Australia, in 2005. BPD was classified as none, grade 1 (mild), grade 2 (moderate), or grade 3 (severe), using 2 commonly accepted definitions: 1) Jobe2001, and 2) Higgins2018, and our own 3) Victorian Infant Collaborative Study (VICS) 2005, adapted from Jensen2019. Outcomes included major neurodevelopmental disability, low IQ and academic achievement, poor motor function, and poor respiratory function as assessed by spirometry. Outcomes for children with each grade of BPD were compared with children with no BPD. RESULTS: Of the 218 survivors, 132 (61%) had BPD on Jobe2001 criteria, and 113 (52%) had BPD on both Higgins2018 and VICS2005 criteria. Grade 1 on any criteria was not associated with any adverse neurodevelopmental outcomes. Grade 1 on both Higgins2018 and VICS2005 was associated with reduced spirometry, grade 2 on both Higgins2018 and VICS2005, and grade 3 on all criteria were associated with increased risk for both adverse neurodevelopmental and respiratory outcomes. CONCLUSIONS: Compared with no BPD, receiving additional oxygen up to 29% but no positive pressure support at 36 weeks' postmenstrual age increased the risk of abnormal respiratory function but not adverse neurodevelopment. Receiving ≥30% oxygen or any positive pressure support at 36 weeks increased the risk of both adverse outcomes.

Obstetrical and neonatal outcomes in patients with surgically repaired heart disease.

BACKGROUND: Congenital and acquired heart disease complicate 1% to 4% of pregnancies in the United States. Beyond the risks of the underlying maternal congenital heart disease, cardiac surgery and its sequelae, such as surgical scarring resulting in higher rates of arrhythmias and implanted valves altering anticoagulation status, have potential implications that could affect gestation and delivery. OBJECTIVE: This study aimed to investigate whether history of maternal cardiac surgery is associated with adverse obstetrical or neonatal outcomes compared with patients without a history of cardiac disease or surgery, considered "healthy controls." STUDY DESIGN: This is a secondary analysis of retrospective cohort studies performed at a tertiary care facility in the United States comparing obstetrical outcomes in patients with a history of open cardiac surgery who delivered from January 2007 to December 2018 with healthy controls, who delivered from April 2020 to July 2020. There were 74 pregnancies in 61 patients with a history of open cardiac surgery that were compared with pregnancies in healthy controls. Of the 74 pregnancies, 65 were successfully matched based on gestational age to controls at a 1:3 (case-to-control) ratio. The remainder of cases were matched at a 1:2 or 1:1 ratio; therefore, a total of 219 control pregnancies were included in the analysis. Our primary outcome was the incidence of hypertensive disorders of pregnancy, as well as cesarean delivery, in patients with a history of open cardiac surgery compared with healthy controls. Our secondary outcome was the incidence of low-birthweight neonates in patients with a history of open cardiac surgery compared with healthy controls. RESULTS: Patients with a history of cardiac surgery were not more likely to have any hypertensive disorder diagnosed than healthy controls. Patients with a history of cardiac surgery were more likely to have an operative delivery (P<.0001) but equally likely to have a cesarean delivery (P=.528) compared with healthy controls. Birthweight was not statistically different of 2655±808 g in neonates born to patients with a history of cardiac surgery vs 2844±830 g born to healthy controls (P=.092). CONCLUSION: Patients with a history of cardiac surgery may not be at higher risk of hypertensive disorder diagnosis during pregnancy. Similarly, most patients with a history of cardiac surgery are also likely not at higher risk of cesarean delivery or low-birthweight neonates.

Low and very low birthweight disadvantage in compulsory education achievement and the transition to upper secondary education in the Finnish birth cohorts of 1987 to 1997.

BACKGROUND: We compared the educational achievements of very low-birthweight (VLBW) and low-birthweight (LBW) adolescents (ages 16 to 19) to those of their normal-birthweight (NBW) peers in the complete Finnish birth cohorts of 1987 to 1997. We focused on three key phases of the education process: the end of compulsory education (9th-grade completion), and the transition to and the completion of upper secondary-level education. METHODS: We used register data on grades, educational transitions and completed education. We employed multiple indicators on the progression of the education process and estimated population-level and within-families linear probability (LPM) models with robustness checks at the population level using logistic regression. We tested whether parental education and the child's sex modify the association between (V)LBW and educational achievement. RESULTS: Results of both descriptive analysis and the population-level and within-family LPM models indicate that (V)LBW is associated with an increased risk of not being able to keep up with the normative education process and to compete for upper secondary education study places at the end of compulsory education. The modifying effect of parental education was robust, whereas that of the child's sex was not. Among (V)LBW students who were able to keep up with the normative education process, (V)LBW was not associated with a lower grade point average or with a meaningfully lower probability of completing upper secondary education by the normative age. CONCLUSIONS: The upper secondary-level educational choices and achievements of the children born with (V)LBW who managed to complete the standard compulsory education curriculum and complete the transition to upper secondary-level education within the expected time did not, in essence, differ from those of the NBW children. Some specific characteristics of the Finnish education system likely contributed to these results, such as the grading at compulsory education being only relatively loosely standardized.