Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study.

BACKGROUND: Pregnant persons are exposed ubiquitously to phthalates and increasingly to chemicals introduced to replace phthalates. In early pregnancy, exposure to these chemicals may disrupt fetal formation and development, manifesting adverse fetal growth. Previous studies examining the consequences of early pregnancy exposure relied on single spot urine measures and did not investigate replacement chemicals. OBJECTIVE: Characterize associations between urinary phthalate and replacement biomarkers in early pregnancy and fetal growth outcomes. METHODS: Analyses were conducted among 254 pregnancies in the Human Placenta and Phthalates Study, a prospective cohort with recruitment 2017-2020. Exposures were geometric mean concentrations of phthalate and replacement biomarkers quantified in two spot urine samples collected around 12- and 14-weeks of gestation. Outcomes were fetal ultrasound biometry (head and abdominal circumferences, femur length, estimated fetal weight) collected in each trimester and converted to z-scores. Adjusted linear mixed effects (single-pollutant) and quantile g-computation (mixture) models with participant-specific random effects estimated the difference, on average, in longitudinal fetal growth for a one-interquartile range (IQR) increase in individual (single-pollutant) or all (mixture) early pregnancy phthalate and replacement biomarkers. RESULTS: Mono carboxyisononyl phthalate and the sums of metabolites of di-n-butyl, di-iso-butyl, and di-2-ethylhexyl phthalate were inversely associated with fetal head and abdominal circumference z-scores. A one-IQR increase in the phthalate and replacement biomarker mixture was inversely associated with fetal head circumference (ß: -0.36 [95% confidence interval: -0.56, -0.15]) and abdominal circumference (-0.31 [-0.49, -0.12]) z-scores. This association was mainly driven by phthalate biomarkers. CONCLUSIONS: Urine concentrations of phthalate biomarkers, but not replacement biomarkers, in early pregnancy were associated with reductions in fetal growth. Though the clinical implications of these differences are unclear, reduced fetal growth contributes to excess morbidity and mortality across the lifecourse. Given widespread global exposure to phthalates, findings suggest a substantial population health burden resulting from early pregnancy phthalate exposure.

Prevalence and risk factors for antimicrobial resistance among newborns with gram-negative sepsis.

INTRODUCTION: Newborn sepsis accounts for more than a third of neonatal deaths globally and one in five neonatal deaths in Ethiopia. The first-line treatment recommended by WHO is the combination of gentamicin with ampicillin or benzylpenicillin. Gram-negative bacteria (GNB) are increasingly resistant to previously effective antibiotics. OBJECTIVES: Our goal was to estimate the prevalence of antibiotic-resistant gram-negative bacteremia and identify risk factors for antibiotic resistance, among newborns with GNB sepsis. METHODS: At a tertiary hospital in Ethiopia, we enrolled a cohort pregnant women and their newborns, between March and December 2017. Newborns who were followed up until 60 days of life for clinical signs of sepsis. Among the newborns with clinical signs of sepsis, blood samples were cultured; bacterial species were identified and tested for antibiotic susceptibility. We described the prevalence of antibiotic resistance, identified newborn, maternal, and environmental factors associated with multidrug resistance (MDR), and combined resistance to ampicillin and gentamicin (AmpGen), using multivariable regression. RESULTS: Of the 119 newborns with gram-negative bacteremia, 80 (67%) were born preterm and 82 (70%) had early-onset sepsis. The most prevalent gram-negative species were Klebsiella pneumoniae 94 (79%) followed by Escherichia coli 10 (8%). Ampicillin resistance was found in 113 cases (95%), cefotaxime 104 (87%), gentamicin 101 (85%), AmpGen 101 (85%), piperacillin-tazobactam 47 (39%), amikacin 10 (8.4%), and Imipenem 1 (0.8%). Prevalence of MDR was 88% (n = 105). Low birthweight and late-onset sepsis (LOS) were associated with higher risks of AmpGen-resistant infections. All-cause mortality was higher among newborns treated with ineffective antibiotics. CONCLUSION: There was significant resistance to current first-line antibiotics and cephalosporins. Additional data are needed from primary care and community settings. Amikacin and piperacillin-tazobactam had lower rates of resistance; however, context-specific assessments of their potential adverse effects, their local availability, and cost-effectiveness would be necessary before selecting a new first-line regimen to help guide clinical decision-making.