Being a First Nations baby is not independently associated with low birthweight in a large metropolitan health service.

AIM: To examine low birth weight (LBW) in First Nations babies born in a large metropolitan health service in Queensland, Australia. MATERIALS AND METHODS: A retrospective population-based study using routinely collected data from administrative data sources. All singleton births in metropolitan health services, Queensland, Australia of ≥20 weeks gestation or at least 400 g birthweight and had information on First Nations status and born between 2019 and 2021 were included. The study measured birthweight and birthweight z-score, and also identified the predictors of LBW. Multivariate regression models were adjusted by demographic, socioeconomic and perinatal factors. RESULTS: First Nations babies had higher rates of LBW (11.4% vs 6.9%, P < 0.001), with higher rates of preterm birth (13.9% vs 8.8%, P < 0.001). In all babies, the most important factors contributing to LBW were: maternal smoking after 20 weeks of gestation; maternal pre-pregnancy underweight (body mass index <18.5 kg/m2); nulliparity; socioeconomic disadvantage; geographical remoteness; less frequent antenatal care; history of cannabis use; pre-existing cardiovascular disease; pre-eclampsia; antepartum haemorrhage; and birth outcomes including prematurity and female baby. After adjusting for all contributing factors, no difference in odds of LBW was observed between First Nations and non-First Nation babies. CONCLUSIONS: First Nations status was not an independent factor influencing LBW in this cohort, after adjustment for identifiable factors. The disparity in LBW relates to modifiable risk factors, socioeconomic disadvantage, and prematurity. Upscaling culturally safe maternity care, focusing on modifiable risk factors is required to address LBW in Australian women.

A case report of spontaneous gastric perforation in a premature and low-birth weight neonate.

INTRODUCTION: Spontaneous gastric perforation of the neonate is a rare phenomenon with a high risk of mortality. Despite an uncertain etiology, an association with prematurity and low-birth weight has been demonstrated. Prompt surgical repair and intensive care remain imperative to survival. PRESENTATION OF CASE: A premature, low-birth weight male was born at 32 weeks and admitted to the NICU for respiratory distress syndrome. Forty-eight hours after birth he developed abdominal distention and an abdominal radiograph demonstrated pneumoperitoneum. Antibiotics were initiated and he was taken for emergent operative exploration. A 3 cm longitudinal perforation was identified in the greater curvature of the stomach. A two-layered repair was performed and a protective Stamm gastrostomy created. On postoperative day 10, an upper gastrointestinal contrast study demonstrated no evidence of leakage. After sustained clinical improvement, the initiation of oral feeding, and continued weight gain, the neonate was successfully discharged home. DISCUSSION: The etiology of spontaneous gastric perforation remains a debate with several proposed mechanisms. In most cases, the neonate will present with abdominal distention and emesis. Although presentation and evidence of pneumoperitoneum on abdominal radiograph are suspicious for this pathology, definitive diagnosis is confirmed during operative exploration. Dedicated intensive care and prompt surgical repair are paramount to survival. Despite decreasing mortality rates, premature and low-birth weight neonates continue to have the lowest rates of survival. CONCLUSION: We present a rare case of a premature, low-birth weight neonate who developed spontaneous gastric perforation and was successfully rescued using a coordinated multidisciplinary approach enabling prompt diagnosis and surgical repair.

Exposure to indoor air pollution and adverse pregnancy outcomes in low and middle-income countries: a systematic review and meta-analysis.

Introduction: Exposure to indoor air pollution such as biomass fuel and particulate matter is a significant cause of adverse pregnancy outcomes. However, there is limited information about the association between indoor air pollution exposure and adverse pregnancy outcomes in low and middle-income countries. Therefore, this meta-analysis aimed to determine the association between indoor air pollution exposure and adverse pregnancy outcomes in low and middle-income countries. Methods: International electronic databases such as PubMed, Science Direct, Global Health, African Journals Online, HINARI, Semantic Scholar, and Google and Google Scholar were used to search for relevant articles. The study was conducted according to the updated Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A random effect model at a 95% confidence interval was used to determine the association between indoor air pollution exposure and adverse pregnancy outcomes using STATA version 14. Funnel plot and Higgs I2 statistics were used to determine the publication bias and heterogeneity of the included studies, respectively. Results: A total of 30 articles with 2,120,228 study participants were included in this meta-analysis. The pooled association between indoor air pollution exposure and at least one adverse pregnancy outcome was 15.5% (95%CI: 12.6-18.5), with significant heterogeneity (I2 = 100%; p < 0.001). Exposure to indoor air pollution increased the risk of small for gestational age by 23.7% (95%CI: 8.2-39.3) followed by low birth weight (17.7%; 95%CI: 12.9-22.5). Exposure to biomass fuel (OR = 1.16; 95%CI: 1.12-1.2), particulate matter (OR = 1.28; 95%CI: 1.25-1.31), and kerosene (OR = 1.38; 95%CI: 1.09-1.66) were factors associated with developing at least one adverse pregnancy outcomes. Conclusions: We found that more than one in seven pregnant women exposed to indoor air pollution had at least one adverse pregnancy outcome. Specifically, exposure to particulate matter, biomass fuel, and kerosene were determinant factors for developing at least one adverse pregnancy outcome. Therefore, urgent comprehensive health intervention should be implemented in the area to reduce adverse pregnancy outcomes.

Assessment of Oral Health Status and Pregnancy Outcomes Among Women in Saudi Arabia.

Purpose: Pregnant women witness many changes in the body as well as in the oral cavity with many factors influencing these changes. This study evaluated the relationship between oral health status, perceptions, and pregnancy outcomes. Methods: A cross sectional study design was implemented to recruit a convenience sample of women attending Obstetrics and gynecology department in public hospitals in East and capital city of Saudi Arabia. To collect data, a validated self-administered questionnaire in English and Arabic was used. The questionnaire covered background information, perceived oral health status, and dental visits. Results: About 64.4% of the 481 women recruited had dental problems, 49.7% reported deterioration in their oral health during pregnancy, and 17.5% reported adverse pregnancy outcomes. Only 40.7% of pregnant women rated their oral health as good, and only 22% visited a dentist during their pregnancy. Dentists were the most common source of oral health information (44.1%), followed by social media (38.9%). Dental problems during pregnancy were significantly associated with adverse outcomes (P=0.007). Oral health perceptions of pregnant women, not visiting the dentist during pregnancy, and gingival problems were also significantly associated with adverse pregnancy outcomes (P=0.001). Those with fair to poor oral health were twice as likely to experience adverse pregnancy outcome. Those who intended to visit the dentist during their pregnancy but did not do so, as well as those who did not visit the dentist at all were 12 and 9 times more likely to experience adverse pregnancy outcomes respectively. Conclusion: Dental complaints during pregnancy, oral health perceptions, and a lack of dental visits were all linked to increased likelihood of adverse pregnancy outcomes. There is a need for interprofessional collaboration to dispel myths and encourage oral health care and regular dental visits during pregnancy.

Repair of infracardiac total anomalous pulmonary venous connection in a 902-gram infant with asplenia syndrome after failed umbilical venous catheter intervention.

Ductus venosus stenting via a transumbilical approach for pulmonary venous obstruction in infracardiac total anomalous pulmonary venous connection has been described. In a 902-gram infant who was diagnosed with asplenia syndrome and infracardiac total anomalous pulmonary venous connection, ductus venosus stenting was attempted by a transumbilical approach. However, ductus venosus stenting was discontinued due to bleeding from the portal vein. The bleeding subsided in time spontaneously, and total anomalous pulmonary venous connection repair with pulmonary artery banding was performed on 21 days after birth. To our knowledge, this is the first report that describes total anomalous pulmonary venous connection repair in a neonate under 1000 g body weight. Learning objective: Ductus venosus stenting is an effective palliative option, especially in the presence of high surgical risk, such as heterotaxy syndrome and a low birth weight. However, ductus venosus stenting should carefully be evaluated by assessment of anatomical configuration of umbilical vein and ductus venosus. If ductus venosus stenting is anatomically difficult, primary surgical repair may be an option even in an extremely low birth weight infant.

Fetal Clinical and Paraclinical Outcomes in HIV-Positive Pregnant Women.

Background Adverse pregnancy outcomes in women with human immunodeficiency virus (HIV) infection remain significantly increased. Untreated maternal infection primarily leads to fetal complications, such as intrauterine growth restriction, stillbirth, or preterm birth. Concerning both maternal and fetal complications that can appear in pregnancy associated with HIV infection, the purpose of the study was to determine fetal and maternal demographic characteristics and the correlation between blood count parameters and poor fetal prognosis. Methods We conducted a quantitative study utilizing document review as the data collection method. This study encompassed a cohort of nine HIV-positive pregnant women who delivered at the Obstetrics and Gynecology Department of the University Emergency Hospital in Bucharest from January 1, 2021, to December 31, 2023. A comparative cohort of nine healthy pregnant women who delivered during the same period in the same facility was selected using stratified random sampling. We examined maternal and fetal demographic parameters and neonatal outcomes, reporting them to paraclinical laboratory data. Results The incidence of pregnancy-related HIV infections was 0.16%. The mean age of patients in the selected group was 29.88 ± 5.53. There was no statistically significant correlation between maternal clinical and paraclinical parameters in the HIV-positive and HIV-negative groups. Although there was a slightly negative difference in the fetal weight at birth, the 1-min APGAR (appearance, pulse, grimace, activity, and respiration) score, and the intrauterine growth restriction between the two groups, there was a statistically significant association between admission to the neonatal intensive care unit (NICU) and the neonates from HIV-positive pregnancies. In our study, we observed preterm deliveries in 22.22% of cases, and we did not record any stillbirths. The 1-min APGAR score was correlated with the value of leukocytes in peripheral blood. Vertical transmission was established to be 11.11% independent of maternal blood count parameters. Conclusion HIV infection during pregnancy leads to a higher risk of admission to the NICU. Fetal leukocytosis is indicative of a lower 1-min APGAR score. The primary emphasis of therapeutic intervention during pregnancy should center on vigilant monitoring of maternal viral load and the timely administration of antiretroviral therapy to enhance fetal outcomes.

Post-discharge home kangaroo mother care follow-up study in rural Gujarat.

Background: Continuation of kangaroo mother care (KMC) at home is vital for improved infant survival and development. Hence, it is essential to understand potential enablers and barriers to home KMC provision. Methodology: This observational study was conducted in rural Gujarat. KMC was initiated for all low-birth-weight (LBW) neonates during the hospital stay and were advised to continue home KMC on discharge. The mothers of these LBW neonates were interviewed using a structured questionnaire during follow-up visits or via telephone. Results: A total of 100 mothers were interviewed, and 98 practiced home KMC. Mothers' mean age was 24.41 (±3.1) years, and infants' mean age was 3.48 (±1.81) months. The mean weight of neonates at discharge was 1.85 (±0.28) kg. Out of the 104 neonates (96 singleton pregnancies and four twins), 76 (73.07%) were pre-term. 31% mothers provided 4-6 hours of daily KMC. 60% provided KMC for less than 1 hour during each session, while 36% of mothers provided each KMC session for 1-3 hours. 74% of mothers received family support, and 62% faced difficulties in home KMC provision. 88% of mothers were homemakers, and 53% had other children to care for. 51% mothers pre-maturely discontinued KMC provision. 83% of the mothers reported fatigue or pain during KMC provision. Conclusion: Lack of family support, other household responsibilities, and other children to care for were major barriers leading to pre-mature discontinuation of home KMC.

Prediction of large-for-gestational-age at birth using fetal biometry in type 1 and type 2 diabetes: A retrospective cohort study.

OBJECTIVE: To compare ultrasound-assessed fetal head circumference (HC), abdominal circumference (AC), HC/AC ratio, and estimated fetal weight (EFW) in prediction of large-for-gestational-age (LGA) at birth in pregnancies affected by type 1 (T1DM) and type 2 (T2DM) diabetes. METHODS: This retrospective cohort study included all women with T1DM and T2DM giving birth to singletons between 2010 and 2019 at Aalborg University Hospital, Denmark. Ultrasound scans were performed at 16, 20, 28 and 34 weeks of pregnancy. LGA was defined as birth weight deviation of 15% or greater from the expected for gestational age (≥90th centile). Prediction of LGA was assessed by logistic regression adjusted for maternal characteristics and glycated hemoglobin (HbA1c) and area under the receiver operating characteristics curve (AUC). RESULTS: Among 180 T1DM pregnancies, 118 (66%) had an LGA neonate at birth. At 28 weeks of pregnancy, they were predicted with AUCHC/AC = 0.67, AUCAC = 0.85, and AUCEFW = 0.86. The multivariate analysis did not improve the predictive performance of the HC/AC ratio or AC. Among 87 T2DM pregnancies, 36 (41%) had an LGA neonate at birth. At 28 weeks, they were predicted with AUCHC/AC = 0.73, AUCAC = 0.83, and AUCEFW = 0.87. In T2DM, the multivariate analysis significantly improved the predictive performance for both HC/AC ratio and AC from 20 weeks of pregnancy. CONCLUSION: In T1DM and T2DM pregnancies, LGA is characterized by a general fetal overgrowth including both AC and HC. Therefore, AC and EFW perform better than the HC/AC ratio in the prediction of LGA. In T2DM, as opposed to T1DM, the predictive performance was improved by the inclusion of maternal characteristics and HbA1c in the analysis.

Assessing the causal relationship of birth weight and childhood obesity on osteoarthritis: a Mendelian randomization study.

Obesity is associated with osteoarthritis (OA), but few studies have used fetal origin to explore the association. Our study aims to disentangle the causality between birth weight, childhood obesity, and adult OA using Mendelian randomization (MR). We identified single nucleotide polymorphisms (SNPs) related to birth weight (n = 298,142) and childhood obesity (n = 24,160) from two genome-wide association studies contributed by the Early Growth Genetics Consortium. Summary statistics of OA and its phenotypes (knee, hip, spine, hand, thumb, and finger OA) from the Genetics of Osteoarthritis Consortium (n = 826,690) were used to estimate the effects of SNPs on OA. Multivariable MR (MVMR) was conducted to investigate the independent effects of exposures. It turned out that genetically predicted standard deviation increase in birth weight was not associated with OA. In contrast, there was a marginally positive effect of childhood obesity on total [odds ratio (OR) = 1.07, 95% confidence interval (CI) = 1.00, 1.15 using IVW], knee (OR = 1.13, 95% CI = 1.05, 1.22 using weighted median), hip (OR = 1.13, 95% CI = 1.04, 1.24 using IVW), and spine OA (OR = 1.12, 95% CI = 1.03, 1.22 using IVW), but not hand, thumb, or finger OA. MVMR indicated a potential adulthood body mass index-dependent causal pathway between childhood obesity and OA. In conclusion, no association of birth weight with OA was suggested. Childhood obesity, however, showed a causality with OA in weight-bearing joints, which seems to be a general association of obesity with OA.

Testing the reported long-term advantages of protein-fortified human milk in very low birth weight neonates.

Preterm infants are at-risk for extrauterine growth restriction and downward percentile-crossing between birth and discharge. Increased energy and protein intake through fortification of human milk during the first weeks of life has been associated with improved short-term growth and better developmental outcomes. The aim of this study was to evaluate whether these benefits persist up to children school age. The study was designed as an observational study. During hospitalization, 22 very low birth weight preterm infants were fed with increasing protein fortification of human milk (protein supplemented group, PSG). As a control group (CG), 11 preterm infants were fed with standard nutrition regimen. At children school age (9-11 years), we assessed anthropometric data (weight, height, BMI), global health (renal function), and specific psychological outcomes (Child Behavior Checklist 6-18). A global homogeneity between CG and PSG groups emerged: we found no significant differences in weight, height, and BMI, nor in internalizing symptom outcomes (all ps > 0.05). However, mothers reported significantly higher externalizing symptoms for the PSG infants compared to CG infants. Therefore, neonatal enteral protein supplementation in very low birth weight preterm infants leads to no positive nor adverse consequences in long-term assessment, suggesting that benefits are restricted to the neonatal term and first years of age.

Mycoplasma genitalium in pregnancy, including specific co-infections, is associated with lower birthweight: A prospective cohort study.

BACKGROUND: Mycoplasma genitalium infection in pregnancy is increasingly reported at similar frequencies to other sexually transmitted infections (STIs). Knowledge on its contribution to adverse pregnancy outcomes is very limited, especially relative to other STIs or bacterial vaginosis (BV). Whether M. genitalium influences birthweight remains unanswered. METHODS: Associations between birthweight and M. genitalium and other STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis) and BV in pregnancy were examined in 416 maternal-newborn pairs from a prospective cohort study in Papua New Guinea. FINDINGS: Compared to uninfected women, M. genitalium (-166.9 g, 95% confidence interval [CI]: -324.2 to -9.7 g, p = 0.038) and N. gonorrhoeae (-274.7 g, 95% CI: -561.9 to 12.5 g, p = 0.061) infections were associated with lower birthweight in an adjusted analysis. The association for C. trachomatis was less clear, and T. vaginalis and BV were not associated with lower birthweight. STI prevalence was high for M. genitalium (13.9%), N. gonorrhoeae (5.0%), and C. trachomatis (20.0%); co-infections were frequent. Larger effect sizes on birthweight occurred with co-infections of M. genitalium, N. gonorrhoeae, and/or C. trachomatis. CONCLUSION: M. genitalium is a potential contributor to lower birthweight, and co-infections appear to have a greater negative impact on birthweight. Trials examining the impact of early diagnosis and treatment of M. genitalium and other STIs in pregnancy and preconception are urgently needed. FUNDING: Funding was received from philanthropic grants, the National Health and Medical Research Council, and the Burnet Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Association between Ureaplasma colonization and bronchopulmonary dysplasia defined by different criteria in very low birth weight infants: A retrospective cohort study.

OBJECTIVE: To study the association between Ureaplasma colonization and bronchopulmonary dysplasia (BPD) with different definitions in very low birth weight (VLBW) infants. METHODS: A retrospective cohort study was performed with VLBW infants admitted from January 2019 to October 2021. Neonates with a positive respiratory tract Ureaplasma culture were included in the study group. Control group infants, matched for gestational age (±1 week), birth weight (±100 g), and birth year, had a negative respiratory tract Ureaplasma culture during the same period. The primary outcomes included the incidence and severity of BPD, defined by various criteria. RESULTS: The study included 302 neonates (151 in the study group and 151 in the control group). After adjusting for confounders, Ureaplasma colonization was not associated with BPD as defined by the National Institutes of Health (NIH) in 2001 (adjusted odds ratio [aOR]: 0.820, 95% confidence interval [CI]: 0.362-1.860, p = .635). However, it was associated with BPD as defined by the NIH in 2018 (aOR: 2.490, 95% CI: 1.128-5.497, p = .024) and the Neonatal Research Network (NRN) in 2019 (aOR: 2.352, 95% CI: 1.077-5.134, p = .032). Additionally, VLBW infants with Ureaplasma colonization had a higher risk of moderate-severe BPD according to the NIH 2001 (aOR: 2.352, 95% CI: 1.077-5.134, p = .032), NIH 2018 (aOR: 6.339, 95% CI: 1.686-23.836, p = .006), and NRN 2019 definitions (aOR: 3.542, 95% CI: 1.267-9.904, p = .016). CONCLUSIONS: Ureaplasma colonization is not associated with BPD by the NIH 2001 definition, but is associated with an increased incidence by the NIH 2018 or NRN 2019 definitions.

Impact of gestational diabetes mellitus on neonatal outcomes in small for gestational age infants: a multicenter retrospective study.

OBJECTIVE: To evaluate obstetric and perinatal outcomes among small for gestational age (SGA) infants born to patients diagnosed with Gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A multicenter retrospective cohort study between 2005 and 2021. The perinatal outcomes of SGA infants born to patients with singleton pregnancy and GDM were compared to SGA infants born to patients without GDM. The primary outcome was a composite adverse neonatal outcome. Infants with known structural/genetic abnormalities or infections were excluded. A univariate analysis was conducted followed by a multivariate analysis (adjusted odds ratio [95% confidence interval]). RESULTS: During the study period, 11,662 patients with SGA infants met the inclusion and exclusion criteria. Of these, 417 (3.6%) SGA infants were born to patients with GDM, while 11,245 (96.4%) were born to patients without GDM. Overall, the composite adverse neonatal outcome was worse in the GDM group (53.7% vs 17.4%, p < 0.01). Specifically, adverse neonatal outcomes such as a 5 min Apgar score < 7, meconium aspiration, seizures, and hypoglycemia were independently associated with GDM among SGA infants. In addition, patients with GDM and SGA infants had higher rates of overall and spontaneous preterm birth, unplanned cesarean, and postpartum hemorrhage. In a multivariate logistic regression assessing the association between GDM and neonatal outcomes, GDM was found to be independently associated with the composite adverse neonatal outcome (aOR 4.26 [3.43-5.3]), 5 min Apgar score < 7 (aOR 2 [1.16-3.47]), meconium aspiration (aOR 4.62 [1.76-12.13]), seizures (aOR 2.85 [1.51-5.37]) and hypoglycemia (aOR 16.16 [12.79-20.41]). CONCLUSIONS: Our study demonstrates that GDM is an independent risk factor for adverse neonatal outcomes among SGA infants. This finding underscores the imperative for tailored monitoring and management strategies in those pregnancies.

Nutritional counselling and risk factors for obesity: an observational study in toddlers.

BACKGROUND: Nutrition exerts a fundamental role in the prevention of obesity (OB). The aim of this study was to assess the extent to which well recognized risk factors for early OB can be associated to overweight (OW) or OB under a standardized nutritional approach and surveillance in toddlers. METHODS: The eligible population was represented by 676 toddlers aged 24-36 months, assigned to 18 primary care pediatricians trained on nutritional issues who shared a standardized nutritional approach. Six-hundred-twenty-nine children (333 boys), mean age 27.8 ± 4.2 months were effectively included in this observational study. Parents received nutritional advice with particular emphasis to proteins and sugar composition supported by leaflets and reinforced at each visit. Body mass index was assessed at the age of 24-36 months. The following individual and family risk factors were considered: gestational age, birth weight, eutocic/caesarean delivery, milk feeding history, household smoking or antibiotics exposure, parents' weight, height and educational level. Prevalence of OW/OB was compared to a group of 742 toddlers (373 boys) under usual care. RESULTS: Under a standardized nutritional counselling, 28.1% toddlers were classified as OW/OB compared to 36.9% toddlers under usual care (p = 0.005). In unadjusted models, parental OW/OB was significantly associated to OW/OB in toddlers (p < 0.01), while high birth weight did not reach statistical significance (p = 0.07). In adjusted models, including all the explanatory variables studied, only paternal OW/OB vs. normal weight was significantly associated to OW/OB in toddlers (OR 2.035, 95% confidence interval 1.206-3.436). No protective effect of exclusive breast feeding during the first 6 months of age was demonstrated. CONCLUSIONS: Toddlers under a standardized nutrition counselling focused to limit protein and simple sugars, showed lower prevalence of OW/OB compared to usual care. Healthy promotion activities should take into account the influence of paternal BMI on the offspring adiposity.

Mendelian randomization shows causal effects of birth weight and childhood body mass index on the risk of frailty.

Background: The association between birth weight and childhood body mass index (BMI) and frailty has been extensively studied, but it is currently unclear whether this relationship is causal. Methods: We utilized a two-sample Mendelian randomization (MR) methodology to investigate the causal effects of birth weight and childhood BMI on the risk of frailty. Instrumental variables (p < 5E-08) strongly associated with own birth weight (N = 298,142 infants), offspring birth weight (N = 210,267 mothers), and childhood BMI (N = 39,620) were identified from large-scale genomic data from genome-wide association studies (GWAS). The frailty status was assessed using the frailty index, which was derived from comprehensive geriatric assessments of older adults within the UK Biobank and the TwinGene database (N = 175,226). Results: Genetically predicted one standard deviation (SD) increase in own birth weight, but not offspring birth weight (maternal-specific), was linked to a decreased frailty index (ß per SD increase = -0.068, 95%CI = -0.106 to -0.030, p = 3.92E-04). Conversely, genetically predicted one SD increase in childhood BMI was associated with an elevated frailty index (ß per SD increase = 0.080, 95%CI = 0.046 to 0.114, p = 3.43E-06) with good statistical power (99.8%). The findings remained consistent across sensitivity analyses and showed no horizontal pleiotropy (p > 0.05). Conclusion: This MR study provides evidence supporting a causal relationship between lower birth weight, higher childhood BMI, and an increased risk of frailty.

Gender and sex hormone effects on neonatal innate immune function.

OBJECTIVES: Scientific evidence provides a widened view of differences in immune response between male and female neonates. The X-chromosome codes for several genes important in the innate immune response and neonatal innate immune cells express receptors for, and are inhibited by, maternal sex hormones. We hypothesized that sex differences in innate immune responses may be present in the neonatal population which may contribute to the increased susceptibility of premature males to sepsis. We aimed to examine the in vitro effect of pro-inflammatory stimuli and hormones in neutrophils and monocytes of male and female neonates, to examine the expression of X-linked genes involved in innate immunity and the miRNA profiles in these populations. METHODS: Preterm infants (n = 21) and term control (n = 19) infants were recruited from the Coombe Women and Infants University Hospital Dublin with ethical approval and explicit consent. The preterm neonates (eight female, 13 male) were recruited with a mean gestation at birth (mean ± SD) of 28 ± 2 weeks and corrected gestation at the time of sampling was 30 + 2.6 weeks. The mean birth weight of preterm neonates was 1084 ± 246 g. Peripheral blood samples were used to analyze immune cell phenotypes, miRNA human panel, and RNA profiles for inflammasome and inflammatory genes. RESULTS: Dividing neutrophil results by sex showed no differences in baseline CD11b between sexes among either term or preterm neonates. Examining monocyte CD11b by sex shows, that at baseline, total and classical monocytes have higher CD11b in preterm females than preterm males. Neutrophil TLR2 did not differ between sexes at baseline or following lipopolysaccharide (LPS) exposure. CD11b expression was higher in preterm male non-classical monocytes following Pam3CSK treatment when compared to females, a finding which is unique to our study. Preterm neonates had higher TLR2 expression at baseline in total monocytes, classical monocytes and non-classical monocytes than term. A sex difference was evident between preterm females and term females in TLR2 expression only. Hormone treatment showed no sex differences and there was no detectable difference between males and females in X-linked gene expression. Two miRNAs, miR-212-3p and miR-218-2-3p had significantly higher expression in preterm female than preterm male neonates. CONCLUSIONS: This study examined immune cell phenotypes and x-linked gene expression in preterm neonates and stratified according to gender. Our findings suggest that the responses of females mature with advancing gestation, whereas male term and preterm neonates have very similar responses. Female preterm neonates have improved monocyte activation than males, which likely reflects improved innate immune function as reflected clinically by their lower risk of sepsis. Dividing results by sex showed changes in preterm and term infants at baseline and following LPS stimulation, a difference which is reflected clinically by infection susceptibility. The sex difference noted is novel and may be limited to the preterm or early neonatal population as TLR2 expression on monocytes of older children does not differ between males and females. The differences shown in female and male innate immune cells likely reflect a superior innate immune defense system in females with sex differences in immune cell maturation. Existing human studies on sex differences in miRNA expression do not include preterm patients, and most frequently use either adult blood or cord blood. Our findings suggest that miRNA profiles are similar in neonates of opposite sexes at term but require further investigation in the preterm population. Our findings, while novel, provide only very limited insights into sex differences in infection susceptibility in the preterm population leaving many areas that require further study. These represent important areas for ongoing clinical and laboratory study and our findings represent an important contribution to exiting literature.

Comparison Between Fetal Abdominal Subcutaneous Tissue Thickness and Abdominal Circumference to Predict Large for Gestational Age Neonate in Gestational Diabetes.

Objective: Increased subcutaneous fat deposition in abdomen in large for gestational age (LGA) fetuses of mothers with gestational diabetes mellitus can be measured by fetal abdominal subcutaneous tissue thickness (FASTT) using ultrasound. The current study aimed to evaluate the correlation between FASTT and birth weight and compare FASTT and abdominal circumference (AC) for prediction of LGA babies in gestational diabetes. Materials and methods: 150 term GDM women were enrolled into the study. FASTT was measured weekly. Birth weight was measured immediately after delivery and categorized into SGA, AGA and LGA according to International growth charts. The last FASTT and AC values were recorded for analysis. Correlation statistics was used to determine the relation between FASTT with birth weight and ROC curves were used to compare FASTT and AC for prediction of LGA fetuses. Results: There was weak positive correlation between FASTT and birth weight with Pearson's co-efficient (r) of 0.375. The cut-off value for FASTT to predict LGA fetuses obtained by ROC curve was ≥8.05 mm with sensitivity and specificity of 68.8% and 68.7%. The mean values of FASTT for small for gestational age (SGA), appropriate for gestational age (AGA) and LGA fetuses were significantly different. AUC for FASTT was 0.692 and for AC was 0.755. Conclusion: FASTT had a positive but weak correlation with birth weight. The utility of FASTT as a screening tool may not be impressive. FASTT can discriminate between SGA, AGA and LGA fetuses. AC is a better predictor than FASTT for LGA neonates.

Early- and late-onset candidemia in very low birth weight infants in the Korean neonatal network, 2013-2017.

BACKGROUND: Candidiasis is a critical infection that is associated with very low birth weight (VLBW; <1500 g). This study investigated the characteristics and clinical presentation of candidiasis in Korean VLBW infants according to the onset of candidemia. METHODS: All VLBW infants with candidemia, defined as blood culture-positive candidiasis and registered in a multicenter database with data from 70 neonatal units of the Korean Neonatal Network between 2013 and 2017, were included in this study. Early-onset candidemia (EOC; ≤10 days) and late-onset candidemia (LOC; >10 days) were analyzed. The demographic characteristics, clinical presentations, and outcomes of candidemia were also determined. RESULTS: The overall incidence of candidemia was 2% (209/10,397) and 4% (173/3934) in VLBW and extremely very low birth weight (ELBW; <1000 g) infants, respectively. In ELBW infants, gestational age was significantly younger at EOC than at LOC (P = 0.015). Cesarean section, respiratory distress syndrome, severe bronchopulmonary disease, pulmonary hemorrhage, prior-bacteremia, neonatal seizures, and periventricular leukomalacia were significantly more common in the LOC group than in the EOC group (P < 0.05). The duration of invasive ventilation, total parenteral nutrition, and hospital stay were significantly longer in the LOC group than in the EOC group (P < 0.05). Most infections were caused by Candida spp. (91.8%). The mortality rate of ELBW infants with candidemia was 41%, which was higher than that of those without candidemia (29%) (P < 0.001). Mortality due to infection was also higher in infants with candidemia (55%) than in those without candidemia (15%) (P < 0.001); however, there were no significant differences between the EOC and LOC groups. CONCLUSIONS: LOC was more common than EOC in VLBW infants. Considering the risk factors of LOC, active weaning from invasive ventilators and aggressive enteral feeding are required to decrease LOC. Furthermore, preventing candidemia is necessary to reduce mortality in VLBW infants.

Thermoregulation, incubator humidity, and skincare practices in appropriate for gestational age ultra-low birth weight infants: need for more evidence.

BACKGROUND: Although not universal, active care is being offered to infants weighing < 500 g at birth, referred to as ultra-low birth weight (ULBW) infants appropriate for gestational age. These infants have the greatest risk of dying or developing major morbidities. ULBW infants face challenges related to fluid and heat loss as well as skin injury in the initial days of life from extreme anatomical and physiological immaturity of the skin. Although there is an emerging literature on the outcomes of ULBW infants, there is a paucity of evidence to inform practice guidelines for delivering optimal care to this cohort of infants. DATA SOURCES: A comprehensive review of the literature was performed using the PubMed and Embase databases. Searched keywords included "thermoregulation or body temperature regulation", "incubator humidity", "skin care", "infant, extremely low birth weight" and "ultra-low birth weight infants". RESULTS: Evidences for thermoregulation, incubator humidity, and skincare practices are available for preterm infants weighing < 1500 g at birth but not specifically for ULBW infants. Studies on thermoregulation, incubator humidity, or skincare practices had a small sample size and did not include a sub-group analysis for ULBW infants. Current practice recommendations in ULBW infants are adopted from research in very and/or extremely low birth weight infants. CONCLUSIONS: This narrative review focuses on challenges in thermoregulation, incubator humidity, and skincare practices in ULBW infants, highlights current research gaps and suggests potential developments for informing practices for improving health outcomes in ULBW infants. Video abstract (MP4 1,49,115 kb).

Enteral Feedings Do Not Increase the Risk of NEC in ELBW Infants Undergoing Treatment of Patent Ductus Arteriosus With Acetaminophen.

OBJECTIVE: Acetaminophen (APAP) is an alternative to indomethacin and ibuprofen for treatment of patent ductus arteriosus (PDA). The side effect profile of non-steroidal anti-inflammatory drugs (NSAIDs) presents enteral feeding safety concerns; however, the safety of enteral feeding on APAP is largely unknown. Optimal feeding strategies during pharmacological PDA treatment are unknown, leading to practice variation. This study aims to assess the incidence of adverse gastrointestinal (GI) outcomes in neonates treated with APAP for PDA closure while receiving enteral feedings. METHODS: Single-center retrospective cohort study of 59 extremely low birth weight (ELBW), premature neonates who received APAP for PDA treatment divided into Low Volume (LV; ≤ 20 mL/kg/day) and High Volume (HV; > 20 mL/kg/day) enteral feeding groups. The primary outcome was the incidence of any suspected or confirmed necrotizing enterocolitis (NEC). Timing of nutrition milestones, parenteral nutrition (PN) days, and adverse outcomes (feeding intolerance, liver dysfunction, death prior to discharge) were evaluated. RESULTS: The incidence of suspected or confirmed NEC was 19.5% in the LV group and 13.3% in the HV group (p = 0.593). The HV group reached full feeds 6 days sooner (18 vs 24 days, p = 0.024) and had fewer PN days (17 vs 23.5 days, p = 0.044) with no difference in adverse outcomes. CONCLUSIONS: Provision of > 20 mL/kg/day of enteral feeds during APAP treatment of PDA decreased time to full feeds and PN days compared to trophic feedings (≤ 20 mL/kg/day) with no difference in adverse GI outcomes. Continuing enteral feeding during APAP PDA treatment appears safe while improving achievement of nutritional milestones.