Risk of Adverse Neonatal Outcomes After Combined Prenatal Cannabis and Nicotine Exposure.

Importance: The prevalence of cannabis use in pregnancy is rising and is associated with adverse perinatal outcomes. In parallel, combined prenatal use of cannabis and nicotine is also increasing, but little is known about the combined impact of both substances on pregnancy and offspring outcomes compared with each substance alone. Objective: To assess the perinatal outcomes associated with combined cannabis and nicotine exposure compared with each substance alone during pregnancy. Design, Setting, and Participants: This retrospective population-based cohort study included linked hospital discharge data (obtained from the California Department of Health Care Access and Information) and vital statistics (obtained from the California Department of Public Health) from January 1, 2012, through December 31, 2019. Pregnant individuals with singleton gestations and gestational ages of 23 to 42 weeks were included. Data were analyzed from October 14, 2023, to March 4, 2024. Exposures: Cannabis-related diagnosis and prenatal nicotine product use were captured using codes from International Classification of Diseases, Ninth Revision, Clinical Modification, and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification. Main Outcome and Measures: The main outcomes were infant and neonatal death, infants small for gestational age, and preterm delivery. Results were analyzed by multivariable Poisson regression models. Results: A total of 3 129 259 pregnant individuals were included (mean [SD] maternal age 29.3 [6.0] years), of whom 23 007 (0.7%) had a cannabis-related diagnosis, 56 811 (1.8%) had a nicotine-use diagnosis, and 10 312 (0.3%) had both in pregnancy. Compared with nonusers, those with cannabis or nicotine use diagnoses alone had increased rates of infant (0.7% for both) and neonatal (0.3% for both) death, small for gestational age (14.3% and 13.7%, respectively), and preterm delivery (<37 weeks) (12.2% and 12.0%, respectively). Moreover, risks in those with both cannabis and nicotine use were higher for infant death (1.2%; adjusted risk ratio [ARR], 2.18 [95% CI, 1.82-2.62]), neonatal death (0.6%; ARR, 1.76 [95% CI, 1.36-2.28]), small for gestational age (18.0%; ARR, 1.94 [95% CI, 1.86-2.02]), and preterm delivery (17.5%; ARR, 1.83 [95% CI, 1.75-1.91]). Conclusions and Relevance: These findings suggest that co-occurring maternal use of cannabis and nicotine products in pregnancy is associated with an increased risk of infant and neonatal death and maternal and neonatal morbidity compared with use of either substance alone. Given the increasing prevalence of combined cannabis and nicotine use in pregnancy, these findings can help guide health care practitioners with preconception and prenatal counseling, especially regarding the benefits of cessation.

Neonatal outcomes in women with Multiple Sclerosis - Influence of disease activity: A Danish nationwide cohort study.

BACKGROUND: Maternal Multiple Sclerosis (MS) has been associated with an increased risk of adverse birth outcomes. We hypothesized that active disease during conception and pregnancy plays an important role in this context, which this study aims to address. METHODS: We used the Danish registers to conduct a nationwide cohort study. Information on maternal disease activity during pregnancy was retrieved using proxies from the linked registers (hospitalization, magnetic resonance imaging of the brain, and use of systemic corticosteroids during pregnancy). Neonates, exposed in utero to maternal disease activity constituted the exposed cohort and the unexposed cohort constituted neonates without in utero exposure to maternal disease activity. The examined outcomes were preterm birth, small for gestational age, low 5-minute Apgar score, and major congenital anomalies. In logistic regression models we estimated the odds ratios (OR) with adjustment for confounders such as maternal age, comorbidities, parity, smoking, calendar year of birth, and disease-modifying treatment. RESULTS: Among the study population of 2492 children of mothers with MS we identified 273 (11 %) neonates exposed to maternal disease activity during pregnancy, and 2219 (89 %) neonates without exposure to disease activity. The adjusted odds ratios (aOR) for preterm birth, small for gestational age, low 5-minute Apgar score, and major congenital anomalies among children born to women with disease activity during pregnancy were 0.92 (95 % confidence interval (95 % CI) 0.53-1.60), aOR 1.19 (95 % CI 0.62-2.26), aOR 2.57 (95 % CI 0.93-7.15) and aOR 0.93 (95 % CI 0.48-1.83), respectively. CONCLUSIONS: Women with MS having disease activity during pregnancy did not have a statistically significantly increased risk of adverse neonatal outcomes compared to women with MS without disease activity, which is overall reassuring results. We believe, that this will be useful knowledge for patients and clinicians in planning a pregnancy and preparing a birth plan.

Low-dose diazoxide is safe and effective in infants with transient hyperinsulinism.

OBJECTIVE: Transient hyperinsulinism (THI) is the most common form of recurrent hypoglycaemia in neonates beyond the first week of life. Although self-resolving, treatment can be required. Consensus guidelines recommend the lower end of the diazoxide 5-15 mg/kg/day range in THI to reduce the risk of adverse events. We sought to determine if doses <5 mg/kg/day of diazoxide can be effective in THI. DESIGN, PATIENTS, MEASURMENTS: Infants with THI (duration <6 months) were treated with low-dose diazoxide from October 2015 to February 2021. Dosing was based on weight at diazoxide start: 2 mg/kg/day in infants 1000-2000 g (cohort 1), 3 mg/kg/day in those 2000-3500 g (cohort 2) and 5 mg/kg/day in those >3500 g. RESULTS: A total of 73 infants with THI (77% male, 33% preterm, 52% small-for-gestational age) were commenced on diazoxide at a median age of 11 days (range 3-43) for a median duration of 4 months (0.3-6.8), with no difference between cohorts. The mean effective diazoxide dose was 3 mg/kg/day (range 1.5-10); 35% (26/73) required an increase from their starting dose, including 60% (9/15) of cohort 1. There was no association between perinatal stress risk factors or treatment-related characteristics and dose increase. Adverse events occurred in 13 patients (18%); oedema (12%) and hyponatraemia (5%) were the most common. Two infants developed suspected necrotising enterocolitis (NEC); none had pulmonary hypertension. CONCLUSION: Diazoxide doses <5 mg/kg/day are effective in THI. While the nature of the association between diazoxide and NEC was unclear, other adverse events were mild. We suggest considering starting doses as low as 2-3 mg/kg/day in THI to balance the side effect risk while maintaining euglycaemia.

Validation of Fetal Medicine Foundation competing-risks model for small-for-gestational-age neonate in early third trimester.

OBJECTIVE: To evaluate the new 36-week Fetal Medicine Foundation (FMF) competing-risks model for the prediction of small-for-gestational age (SGA) at an earlier gestation of 30 + 0 to 34 + 0 weeks. METHODS: This was a retrospective multicenter cohort study of prospectively collected data on 3012 women with a singleton pregnancy undergoing ultrasound examination at 30 + 0 to 34 + 0 weeks' gestation as part of a universal screening program. We used the default FMF competing-risks model for prediction of SGA at 36 weeks' gestation combining maternal factors (age, obstetric and medical history, weight, height, smoking status, race, mode of conception), estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI) to calculate risks for different cut-offs of birth-weight percentile and gestational age at delivery. We examined the accuracy of the model by means of discrimination and calibration. RESULTS: The prediction of SGA < 3rd percentile improved with the addition of UtA-PI and with a shorter examination-to-delivery interval. For a 10% false-positive rate, maternal factors, EFW and UtA-PI predicted 88.0%, 74.4% and 72.8% of SGA < 3rd percentile delivered at < 37, < 40 and < 42 weeks' gestation, respectively. The respective values for SGA < 10th percentile were 86.1%, 69.3% and 66.2%. In terms of population stratification, if the biomarkers used are EFW and UtA-PI and the aim is to detect 90% of SGA < 10th percentile, then 10.8% of the population should be scanned within 2 weeks after the initial assessment, an additional 7.2% (total screen-positive rate (SPR), 18.0%) should be scanned within 2-4 weeks after the initial assessment and an additional 11.7% (total SPR, 29.7%) should be examined within 4-6 weeks after the initial assessment. The new model was well calibrated. CONCLUSIONS: The 36-week FMF competing-risks model for SGA is also applicable and accurate at 30 + 0 to 34 + 0 weeks and provides effective risk stratification, especially for cases leading to delivery < 37 weeks of gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Risk of adverse birth outcomes after adolescent and young adult cancer.

BACKGROUND: Many women diagnosed with cancer as adolescents and young adults (AYAs, age 15-39 years) want biological children after cancer but lack information on the potential impact of their cancer history on future reproductive outcomes. We investigated the risk of adverse birth outcomes among AYA cancer survivors. METHODS: We identified insured women diagnosed with AYA breast cancer, thyroid cancer, gynecologic cancers, lymphoma, or melanoma from 2003 to 2016 in the state of North Carolina or the Kaiser Permanente health care systems in northern and southern California. Post-diagnosis births to cancer survivors were each matched with up to 5 births to women without cancer. Risk ratios for preterm birth (<37 completed weeks), very preterm birth (<34 completed weeks), low birth weight (<2500 g), and small for gestational age (SGA, <10th percentile of weight for gestational age) were estimated using modified Poisson regression. RESULTS: Analyses included 1648 births to 1268 AYA cancer survivors and 7879 births to 6066 women without cancer. Overall, risk of preterm birth, very preterm birth, low birth weight, and SGA did not significantly differ between births to women with and without cancer. However, births to women with gynecologic cancers had a significantly increased risk of low birth weight (risk ratio = 1.82; 95% confidence interval: 1.03 to 3.21) and suggested increased risk of preterm birth (risk ratio = 1.59; 95% confidence interval: 0.99 to 2.54). Chemotherapy exposure was not associated with increased risk of adverse birth outcomes. CONCLUSIONS: Women with gynecologic cancers, but not other cancers, had an increased risk of adverse birth outcomes compared to women without cancer.

Use of E-Cigarettes and Cigarettes During Late Pregnancy Among Adolescents.

Importance: Pregnant adolescents sometimes use cigarettes; however, little is known about e-cigarette use among pregnant adolescents, a population with increased health vulnerability. Objective: To examine yearly trends, sociodemographic and pregnancy-related determinants, and the association with small-for-gestational-age (SGA) birth of e-cigarette and/or cigarette use during late pregnancy among adolescents. Design, Setting, and Participants: This cohort study used existing data from the 2016-2021 Pregnancy Risk Assessment Monitoring System on 10 428 US adolescents aged 10 to 19 years who had a singleton birth with complete data on e-cigarette or cigarette use and SGA birth. Exposure: Adolescents reported e-cigarette and cigarette use during the last 3 months of pregnancy. Main Outcomes and Measures: SGA birth (birth weight below the 10th percentile for the same sex and gestational duration) was determined from birth certificates. Multivariable logistic regression was used to compare the odds of SGA birth across pregnant adolescents who exclusively used e-cigarettes, exclusively used cigarettes, used e-cigarettes and cigarettes, or did not use either. Results: Of the 10 428 pregnant adolescents, 72.7% were aged 18 or 19 years; 58.9% self-identified as White and 23.3% as Black; and 69.8% were non-Hispanic. The weighted prevalence of exclusive e-cigarette use during late pregnancy increased from 0.8% in 2016 to 4.1% in 2021, while the prevalence of exclusive cigarette use decreased from 9.2% in 2017 to 3.2% in 2021. The prevalence of dual use fluctuated, ranging from 0.6% to 1.6%. White pregnant adolescents were more likely than those who self-identified as another race and ethnicity to use e-cigarettes (2.7% vs 1.0% for American Indian or Alaska Native adolescents, 0.8% for Asian or other race adolescents, 0.6% for Black adolescents, and 0.7% for multiracial adolescents). Compared with those who did not use either product, adolescents who exclusively used e-cigarettes (16.8% vs 12.9%; confounder-adjusted odds ratio [AOR], 1.68 [95% CI, 0.89-3.18]) or who used cigarettes and e-cigarettes (17.6% vs 12.9%; AOR, 1.68 [95% CI, 0.79-3.53]) had no statistically significant difference in risk of SGA birth. However, adolescents who exclusively used cigarettes had a more than 2-fold higher risk of SGA birth (24.6% vs 12.9%; AOR, 2.51 [95% CI, 1.79-3.52]). Conclusions and Relevance: This cohort study suggests that pregnant adolescents increasingly used e-cigarettes, with the highest use among White adolescents. Results from this analysis found that, unlike cigarette use, e-cigarette use during late pregnancy was not statistically significantly associated with an increased risk of SGA birth among adolescents. Due to the uncertainty of this nonsignificant association, future research could benefit from a larger sample size.

Night work during pregnancy and small for gestational age: a Danish nationwide register-based cohort study.

OBJECTIVE: The aim was to investigate the association between night work during pregnancy and risk of having a small for gestational age (SGA) child. METHODS: This cohort study had payroll data with detailed information on working hours for employees in all Danish administrative regions (primarily hospital employees) between 2007 and 2015, retrieved from the Danish Working Hour Database. Pregnancies, covariates and outcome were identified from the national birth registry. We used logistic regression to investigate the association between intensity and duration of night work during the first 32 pregnancy weeks and SGA. The adjusted model included age, body mass index, socioeconomic status and smoking. Using quantitative bias analysis and G-estimation, we explored potential healthy worker survivor bias (HWSB). RESULTS: The final cohort comprised 24 548 singleton pregnancies in 19 107 women, primarily nurses and medical doctors. None of the dimensions of night work were associated with an increased risk of SGA. We found a tendency towards higher risk of SGA in pregnancies where the women stopped having night shifts during pregnancy. Using G-estimation we found an OR<1 for the association between night work and SGA if all workers continued having night work during pregnancy compared with daywork only. CONCLUSION: We found no increased risk of SGA in association with night work during pregnancy among healthcare workers. G-estimation was not precise enough to estimate the observed indication of HWSB. We need better data on pregnancy discomforts and complications to be able to safely rule out HWSB.

Investigation of (Epi)genetic causes in syndromic short children born small for gestational age.

Intrauterine onset syndromic short stature constitutes a group of diseases that pose challenges in differential diagnosis due to their rarity and clinical as well as molecular heterogeneity. The aim of this study was to investigate the presence of (epi)genetic causes in children born small for gestational age (SGA) and manifesting clinically undiagnosed syndromic short stature. The study group comprised twenty-nine cases selected from the syndromic SGA cohort. Various analyses were performed, including chromosomal microarray (CMA), methylation-specific-multiple ligation probe amplification for chromosomes 6,14 and 20, and whole exome sequencing (WES). Pathogenic copy number variants (CNVs) on chromosomes 2q13, 22q11.3, Xp22.33, 17q21.31, 19p13.13 and 4p16.31 causing syndromic growth disturbance were detected in six patients. Maternal uniparental disomy 14 was identified in a patient. WES was performed in the remaining 22 patients, revealing pathogenic variants in nine cases; six were monoallelic (ACAN, ARID2, NIPBL, PIK3R1, SMAD4, BRIP1), two were biallelic (BRCA2, RFWD3) and one was hemizygous (HUWE1). Seven of these were novel. Craniofacial dysmorphism, which is an important clue for the diagnosis of syndromes, was very mild in all patients. This study unveiled, for the first time, that ARID2 mutatios can cause syndromic SGA. In conclusion, a high (55.2%) diagnosis rate was achieved through the utilization of CMA, epigenetic and WES analyzes; 15 rare syndromes were defined, who were born with SGA and had atypical and/or mild dysmorphic findings. This study not only drew attention to the association of some rare syndromes with SGA, but also introduced novel genes and CNVs as potential contributors to syndromic SGA.

Case Report: Severe McCune-Albright syndrome presenting with neonatal Cushing syndrome: navigating through clinical obstacles.

Background: Café-au-lait skin macules, Cushing syndrome (CS), hyperthyroidism, and liver and cardiac dysfunction are presenting features of neonatal McCune-Albright syndrome (MAS), CS being the rarest endocrine feature. Although spontaneous resolution of hypercortisolism has been reported, outcome is usually unfavorable. While a unified approach to diagnosis, treatment, and follow-up is lacking, herein successful treatment and long-term follow-up of a rare case is presented. Clinical case: An 11-day-old girl born small for gestational age presented with deterioration of well-being and weight loss. Large hyperpigmented macules on the trunk, hypertension, hyponatremia, hyperglycemia, and elevated liver enzymes were noted. ACTH-independent CS due to MAS was diagnosed. Although metyrapone (300 mg/m2/day) was started on the 25th day, complete remission could not be achieved despite increasing the dose up to 1,850 mg/m2/day. At 9 months, right total and left three-quarters adrenalectomy was performed. Cortisol decreased substantially, ACTH remained suppressed, rapid tapering of hydrocortisone to physiological dose was not tolerated, and supraphysiological doses were required for 2 months. GNAS analysis from the adrenal tissue showed a pathogenic heterozygous mutation. During 34 months of follow-up, in addition to CS due to MAS, fibrous dysplasia, hypophosphatemic rickets, and peripheral precocious puberty were detected. She is still regularly screened for other endocrinopathies. Conclusion: Neonatal CS due to MAS is extremely rare. Although there is no specific guideline for diagnosis, treatment, or follow-up, addressing side effects and identifying treatment outcomes will improve quality of life and survival.

Reduced pulmonary oxygen diffusion at 36 weeks of postmenstrual age in small-for-gestational-age preterm infants of less than 32 weeks without bronchopulmonary dysplasia.

BACKGROUND: Small-for-gestational-age (SGA) preterm infants are at increased risk of developing bronchopulmonary dysplasia (BPD). There is limited information on pulmonary oxygen diffusion of SGA preterm infants, particularly in those without BPD. OBJECTIVE: To compare the pulmonary oxygen diffusion of SGA to that of appropriate-for-gestational-age (AGA) preterm infants without BPD. STUDY DESIGN: Preterm infants with a gestational age (GA) between 24.0 and 31.6 weeks were studied. The oxygen saturation (SpO2 ), fraction to inspired oxygen (FiO2 ), and the SpO2 to FiO2 ratio (SFR) were compared between SGA and AGA infants. The association between SGA and SFR at 36 weeks was assessed using a multiple regression analysis. In the subgroup without BPD, SGA were match-paired for GA and gender with AGA infants. RESULTS: We analyzed 1189 infants surviving at 36 weeks: 194 (16%) were SGA and 995 (84%) AGA. The incidence of BPD was significantly higher in SGA than AGA infants (32% vs. 13%; p = .000). Out of the 995 infants without BPD, 132 (13%) were SGA and 863 (87%) AGA. SGA was negatively associated with the SFR value at 36 weeks, independently from BPD. SGA infants without BPD had significantly higher (better) SFR at birth, but lower (worse) SpO2 and SFR and from 33 to 36 weeks than their matched AGA counterpart. At 36 weeks, median SpO2 and SFR values were 97.7 versus 98.4 (p = .006) and 465 versus 468 (p = .010) in match-paired SGA and AGA, respectively. CONCLUSION: Among preterm infants of less than 32 weeks and without BPD, SGA infants had a reduced pulmonary oxygen diffusion at 36 weeks in comparison with AGA infants.

Relationship between kisspeptin levels in the third trimester and late-onset fetal growth restriction: A case-control study.

INTRODUCTION: We aimed to investigate whether maternal serum kisspeptin levels are associated with late-onset FGR and contribute to adverse perinatal outcomes. METHOD: In this case-control study, a total of 90 pregnant women admitted to the perinatology clinic were enrolled. Forty-five of them were diagnosed with FGR and 45 women with healthy pregnancies formed the control group. Maternal serum levels of kisspeptin 1 were compared. RESULTS: Median kisspeptin1 serum levels were higher in the group of patients with FGR according to gestational age than in the control group [79.4(3.9-230.2) pg/mL vs. 39.8(0.4-188.3) pg/mL; p = 0.001]. The optimal cut-off value for kisspeptin1 was 30.32 pg/mL, with a positive predictive value of 64.6% (95% CI; 0.54-0.86), negative predictive value of 87.5% (95% CI; 0.44-0.72), positive likelihood ratio 1.75 (95% CI; 1.31-2.32), negative likelihood ratio 0.14 (95% CI; 0.04-0.44). DISCUSSION: Kisspeptin1 differed significantly in late-onset FGR compared with the control group. This difference from the control group can be used to estimate late-onset FGR.

Explaining the Link Between Paternal Socioeconomic Position and Small for Gestational Age Birth: The Effect of Maternal Unhealthy Behaviors.

OBJECTIVE: To determine the proportion of small for gestational age (weight < 10th percentile, SGA) births among fathers with lifelong low (compared to high) socioeconomic position (SEP) attributable to white and African-American women's unhealthy pregnancy-related behaviors. METHODS: Oaxaca-Blinder decomposition methods were conducted on the Illinois transgenerational dataset of infants (1989-1991) and their Chicago-born parents (1956-1976) with appended US census income data. The neighborhood income of father's residence at the time of his birth and at the time of his infant's birth were used to estimate his lifetime SEP. Maternal unhealthy pregnancy-related behaviors were defined as cigarette smoking, inadequate prenatal care, and/or low weight gain during pregnancy. RESULTS: Among African-American women, births (n = 4426) to fathers with lifetime low SEP had an SGA rate of 14.8% compared to 12.1% for those (n = 365) born to fathers with lifetime high SEP (p < 0.0001). Among white women, births (n = 1430) to fathers with lifetime low SEP had an SGA rate of 9.8% compared to 6.2% for those (n = 9141) born to fathers with lifetime high SEP (p < 0.0001). Adjusting for maternal age, marital status, education, and parity, African-American and white women's unhealthy pregnancy behaviors accounted for 25% and 33%, respectively, of the disparity in SGA rates among infants of lifetime low (compared to high) SEP fathers. CONCLUSION: A significant proportion of the disparity in SGA rates between fathers with lifelong low (compared to high) SEP is explained in both races by maternal unhealthy pregnancy behaviors.

Distribución espacial y tendencia secular (1991-2014) de nacidos pequeños para la edad gestacional en Jujuy / Spatial distribution and secular trend (1991­2014) of small for gestational age infants born in Jujuy

Introducción. El feto que no alcanza el potencial de crecimiento esperado en el útero se considera pequeño para la edad gestacional (PEG). Esta restricción depende de factores genéticos y/o ambientales; la altura geográfica es uno muy relevante. Este trabajo analiza la distribución espacial de las prevalencias de PEG y su tendencia secular en Jujuy (1991-2014). Materiales y métodos. Se analizaron los registros de 308 469 nacidos vivos de Jujuy (Dirección de Estadísticas e Información de Salud). Se estimaron prevalencias de PEG (peso/edad gestacional

Introduction. A fetus that does not reach the expected growth potential in utero is considered small for gestational age (SGA). Such restriction depends on genetic and/or environmental factors, being altitude a very relevant factor. This study analyzes the spatial distribution of the prevalence of SGA and its secular trend in Jujuy (1991­2014). Materials and methods. The records of 308 469 live births in Jujuy (Health Statistics and Information Department) were analyzed. The prevalence of SGA (weight/gestational age < P10 and < P3) was estimated for sex according to the INTERGROWTH-21 st standard in the ecoregions of Jujuy (Valle and Ramal ­less than 2000 MASL­, Puna, and Quebrada) across 3 periods (1991­2000, 2001­2009, 2010­2014) and proportions were compared. The secular trend was assessed using the Joinpoint regression analysis. Results. The overall prevalence of SGA was 2.3% (< P3) and 7% (< P10). Significantly higher values were observed in Puna and Quebrada in both SGA categories and across all periods. Only in Valle, significant differences were observed between sexes across all periods. The prevalence of SGA showed a significant downward secular trend at a provincial and regional level, and this was greater in Quebrada (5.2% < P3 and 3.5% < P10). Conclusions. A consistent and significant decrease in the prevalence of SGA has been observed since the 1990s in Jujuy, where altitude is itself a determining factor of size at birth, since the Puna and Quebrada regions showed the highest prevalence of SGA during the entire period.

Association between prenatal socioeconomic disadvantage, adverse birth outcomes, and inflammatory response at birth.

Prenatal socioeconomic disadvantage is associated with inflammation in mid- to late-life, yet whether a pro-inflammatory phenotype is present at birth and the role of adverse birth outcomes in this pathway remains unclear. We utilized data on prenatal socioeconomic disadvantage at the individual- (i.e., mother's and father's education level, insurance type, marital status, and Women, Infants, and Children benefit receipt) and census-tract level as well as preterm (< 37 weeks gestation) and small-for-gestational-age (SGA) (i.e., < 10th percentile of sex-specific birth weight for gestational age) birth status, and assessed inflammatory markers (i.e., C-reactive protein, serum amyloid p, haptoglobin, and α-2 macroglobulin) in archived neonatal bloodspots from a Michigan population-based cohort of 1000 neonates. Continuous latent variables measuring individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage were constructed and latent profile analysis was used to create a categorical inflammatory response variable (high versus low) based on continuous inflammatory marker levels. Structural equation models were used to estimate the total and direct effect of prenatal socioeconomic disadvantage on the inflammatory response at birth as well as indirect effect via preterm or SGA birth (among term neonates only), adjusting for mother's age, race/ethnicity, body mass index, smoking status, comorbidities, and antibiotic use/infection as well as grandmother's education level. There was a statistically significant total effect of both individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage on high inflammatory response among all neonates as well as among term neonates only, and a positive but not statistically significant direct effect in both groups. The indirect effects via preterm and SGA birth were both negative, but not statistically significant. Our findings suggest prenatal socioeconomic disadvantage contributes to elevated neonatal inflammatory response, but via pathways outside of these adverse birth outcomes.

Use of pregnancy personalised follow-up in case of maternal social vulnerability to reduce prematurity and neonatal morbidity.

BACKGROUND: Social deprivation is a major risk factor of adverse pregnancy outcomes. Yet, there is few studies evaluating interventions aiming at reducing the impact of social vulnerability on pregnancy outcomes. OBJECTIVE: To compare pregnancy outcomes between patients that received personalized pregnancy follow-up (PPFU) to address social vulnerability versus standard care. METHODS: Retrospective comparative cohort in a single institution between 2020 and 2021. A total of 3958 women with social vulnerability that delivered a singleton after 14 gestational weeks were included, within which 686 patients had a PPFU. Social vulnerability was defined by the presence of at least one of the following characteristics: social isolation, poor or insecure housing conditions, no work-related household income, and absence of standard health insurance (these four variables were combined as a social deprivation index (SDI)), recent immigration (< 12 month), interpersonal violence during pregnancy, being handicaped or minor, addiction during pregnancy. Maternal characteristics and pregnancy outcomes were compared between patients that received PPFU versus standard care. The associations between poor pregnancy outcomes (premature birth before 37 gestational weeks (GW), premature birth before 34 GW, small for gestational age (SGA) and PPFU were tested using multivariate logistic regression and propensity score matching. RESULTS: After adjustment on SDI, maternal age, parity, body mass index, maternal origin and both high medical and obstetrical risk level before pregnancy, PPFU was an independent protective factor of premature birth before 37 gestational weeks (GW) (aOR = 0.63, 95%CI[0.46-0.86]). The result was similar for premature birth before 34 GW (aOR = 0.53, 95%CI [0.34-0.79]). There was no association between PPFU and SGA (aOR = 1.06, 95%CI [0.86 - 1.30]). Propensity score adjusted (PSa) OR for PPFU using the same variables unveiled similar results, PSaOR = 0.63, 95%CI[0.46-0.86] for premature birth before 37 GW, PSaOR = 0.52, 95%CI [0.34-0.78] for premature birth before 34 GW and PSaOR = 1.07, 95%CI [0.86 - 1.33] for SGA. CONCLUSIONS: This work suggests that PPFU improves pregnancy outcomes and emphasizes that the detection of social vulnerability during pregnancy is a major health issue.

A Small-for-Gestational-Age Infant with MIRAGE Syndrome Who Developed Heat Stroke and Rhabdomyolysis due to Severe Temperature Instability.

MIRAGE syndrome is characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. This report describes heat stroke and rhabdomyolysis caused by anhidrosis as a symptom of MIRAGE syndrome in a small-for-gestational-age (SGA) female neonate born at 32 weeks of gestation (birth weight, 911 g [-3.8 SD]). She developed severe temperature instability with anhidrosis, growth failure, mild developmental delay, hypothyroidism, and intractable enteropathy. On day 156, her temperature reached 42.0°C; her fever persisted for 2 h with prolonged irritability. Her serum creatine kinase level increased to a peak value of 12,716 (normal range, 43-321) IU/L. The clinical feature was diagnosed as rhabdomyolysis caused by heat stroke, which resulted from physical exertion with anhidrosis. Her SAMD9 variant was c.2945G>A, p. (Arg982His). Neonatologists should be aware of MIRAGE syndrome as a differential diagnosis of SGA with temperature instability.

The association between maternal influenza vaccination during pregnancy and adverse birth outcomes in the United States: Pregnancy risk Assessment Monitoring System (PRAMS).

OBJECTIVE: Influenza vaccination during pregnancy is highly recommended. We examined the association between maternal influenza vaccination and adverse birth outcomes. METHODS: This cross-sectional study used data from the Pregnancy Risk Assessment Monitoring System (PRAMS) during 2012-2017. The primary exposure was the receipt of influenza vaccination during pregnancy. Low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) were the primary outcomes. We conducted multivariable logistic regression models to estimate the adjusted odds ratios (AOR) and 95% confidence intervals (CI). Covariates used to adjust confounding included maternal age, marital status, education, race and ethnicity, insurance status before pregnancy, and smoking status. For a subgroup in 2012-2015, we analyzed the association between influenza vaccination in each trimester and adverse birth outcomes. RESULTS: During 2012-2017, compared with unvaccinated women, women vaccinated during pregnancy had a lower risk of LBW and PTB. During 2012-2015, maternal influenza vaccination in the 1st and 3rd trimesters was associated with a reduced risk of LBW and PTB, and vaccination in the 3rd trimester had a greater protective effect than in the 1st trimester. Influenza vaccination was not associated with SGA regardless of trimester. CONCLUSIONS: Our findings suggest that influenza vaccination during pregnancy is a safe and effective way to protect newborns.

Role of birthweight discordance in preterm twins' outcomes in the Korean neonatal network.

BACKGROUND: Twin pregnancies can be complicated by birthweight (BW) discordance. We analyzed the impact of BW discordance on clinical outcomes of very-low-birthweight (VLBW) twins. METHODS: The study population was preterm infants in the Korean Neonatal Network registry. Multivariate logistic regression analyses were used to determine the contribution of BW discordance on respiratory morbidities and mortality of VLBW infants. Also, we assessed the effect of small for gestational age (SGA) on morbidity and mortality in discordant twins (DTs) and compared separately the clinical outcomes of smaller and larger DTs with different singletons matched for perinatal factors including BW percentile. RESULTS: A total of 935 twin pairs [1548 concordant twins (CTs) and 322 DTs] were included. BW discordance was associated with increased odds of moderate bronchopulmonary dysplasia, mortality, and composite outcomes. Compared with the CTs, the smaller, but not larger, DTs had greater odds of morbidities and mortality. DTs had higher odds of adverse neonatal outcome when combined with SGA. Meanwhile, DTs had morbidities and mortality similar to singletons matched for BW percentile. CONCLUSION: BW discordance in VLBW twins adversely affects neonatal mortality or respiratory morbidity which is predominant in smaller DTs. The impact of BW discordance could be increased through SGA.