The association between placental histopathology and autism spectrum disorder.

INTRODUCTION: Research suggests that autism spectrum disorder (ASD) has its origins in utero. This study examines the association between evidence of placental histopathology and ASD. METHODS: Administrative claims data and medical records data were used to identify ASD cases (N = 55) and matched controls (N = 199) born at New York Methodist Hospital between 2007 and 2014 and subsequently seen in affiliated pediatrics clinics. Placentas from all births during this time period were reviewed as part of routine care. Data were analyzed using conditional logistic regression to account for the matched (gender, gestational age, and birth weight) design. RESULTS: Acute placental inflammation, regardless of type was associated with an increased risk of ASD (odds ratio [OR] = 3.14, 95% CI = 1.39, 6.95). Chronic uteroplacental vasculitis (OR = 7.13; 95% CI = 1.17, 43.38), the fetal inflammatory response in the chorionic plate vessels (OR = 5.12; 95% CI = 2.02, 12.96), and maternal vascular malperfusion pathology (OR = 12.29; 95% CI = 1.37, 110.69) were associated with an increased risk of ASD. Placental villous edema was associated with a decreased risk of ASD (OR = 0.05; 95% CI = 0.0005, 0.42). In subanalyses among male placentas acute inflammation overall, fetal inflammatory response in the chorionic plate vessels, and maternal vascular malperfusion pathology remained significantly associated with an increased risk of ASD whereas placental villous edema remained associated with a decreased risk of ASD. DISCUSSION: Histologic evidence of placental inflammation and maternal vascular malperfusion pathology are associated with ASD.

Methods to decrease variability in histological scoring in placentas from a cohort of preterm infants.

OBJECTIVE: Reliable semiquantitative assessment of histological placental acute inflammation is problematic, even among experts. Tissue samples in histology slides often show variability in the extent and location of neutrophil infiltrates. We sought to determine whether the variability in pathologists' scoring of neutrophil infiltrates in the placenta could be reduced by the use of 'regions of interest' (ROIs) that break the sample into smaller components. DESIGN: ROIs were identified within stained H&E slides from a cohort of 56 women. ROIs were scored using a semiquantitative scale (0-4) for the average number of neutrophils by at least two independent raters. SETTING: Preterm singleton births at Yale New Haven Hospital. PARTICIPANTS: This study used stained H&E placental slides from a cohort of 56 women with singleton pregnancies who had a clinically indicated amniocentesis within 24 hours of delivery. PRIMARY AND SECONDARY OUTCOME MEASURES: Interrater agreement was assessed with the intraclass correlation coefficient (ICC) and log-linear regression. Predictive validity was assessed using amniotic fluid protein profile scores (neutrophil defensin-2, neutrophil defensin-1, calgranulin C and calgranulin A). RESULTS: Excellent agreement by the ICC was found for the average neutrophil scores within a region of interest. Log-linear analyses suggest that even where there is disagreement, responses are positively associated along the diagonal. There was also strong evidence of predictive validity comparing pathologists' scores with amniotic fluid protein profile scores. CONCLUSIONS: Agreement among observers of semiquantitative neutrophil scoring through the use of digitised ROIs was demonstrated to be feasible with high reliability and validity.

Increasing maternal body mass index during pregnancy increases neonatal intensive care unit admission in near and full-term infants.

BACKGROUND: Obesity is becoming an increasingly commonplace health problem. Obesity during pregnancy is important because the condition adversely affects not only the mother, but also the developing fetus and the newborn. OBJECTIVE: The primary objective of this study was to evaluate the association between maternal body mass index (mBMI) at the time of delivery and neonatal intensive care unit (NICU) admission of offspring and to analyze the role of possible confounding variables that are often associated with obesity. Comorbidities, such as gestational diabetes mellitus (DM), hypertension (HT) and/or pre-eclampsia (PEC), are more common in more obese mothers, as is a higher association of obesity among non-Caucasian patients. METHODS: Using a retrospective cohort design, 1736 mothers and their singleton live-born at ≥35 weeks' gestation were analyzed for mBMI, maternal conditions of DM, HT and/or PEC, and whether NICU care was required and the reason for NICU admission. RESULTS: NICU admission rate was significantly associated with maternal obesity. In comparing women with mBMI < 30 versus mBMI ≥ 30, OR was 1.39 (p = 0.045); OR increased to 1.76 (p = 0.006) in comparing patients with mBMI ≥ 35. mBMI was significantly associated with an increased rate of maternal DM, HT and PEC (p < 0.05 each); however, NICU admission rate was not correlated with DM, HT or PEC. The relationship between NICU admission and mBMI was significant in Caucasian mothers versus a borderline significance in African-American mothers (p = 0.035 versus p = 0.05). After controlling for neonatal hypoglycemia (NH) as the reason for admission to the NICU, no mBMI-NICU association persisted. The rate of infants with NH increased in higher mBMI groups, independent of maternal DM diagnosis. CONCLUSION: This study demonstrated a significant association between higher mBMI groups and NICU admissions independent of diagnosis of maternal comorbidities. However, accounting for NH eliminating this association suggests a pre-clinical diabetic pathology in obese women that affects newborn outcome. Despite increased percentage of nonwhite mothers in higher mBMI groups, African-American race does not seem to be a significant contributing factor in the increased rate of NICU admission in our population.

A young adult Jehovah's Witness with severe anemia.

Two of the most ethically complex situations in pediatrics are those involving families whose religious beliefs preclude the provision of life-sustaining treatment and those involving young adults who have reached the age of legal majority and who face decisions about life-sustaining treatment. This month's "Ethics Rounds" presents a case in which these 2 complexities overlapped. An 18-year-old Jehovah's Witness with sickle cell disease has life-threatening anemia. She is going into heart failure. Her doctors urgently recommend blood transfusions. The young woman and her family adamantly refuse. Should the doctors let her die? Is there any alternative?

Histologic chorioamnionitis as a consideration in the management of newborns of febrile mothers.

INTRODUCTION: Chorioamnionitis (CA) presents a risk for neonatal sepsis, but its diagnosis remains a challenge. Maternal fever is often used as a clinical predictor of infection, but may be affected by other factors. There is no consensus among neonatologists regarding the length of treatment of babies born to febrile mothers with negative blood culture, but whose placentas are positive for the presence of histologic CA (HCA). OBJECTIVES: A prospective observational cohort study was conducted on term infants to determine the association of HCA with C-reactive protein (CRP) and elevated immature/total neutrophil (I/T) ratio and other perinatal factors. METHODS: I/T ratio, CRP, blood culture and placental pathology were performed on 100 infants born to mothers with temperature ≥ 100.4 °F. Placental pathology performed on 100 control infants born to afebrile mothers. RESULTS: There was a significant association between HCA and maternal fever (MF). The presence of elevated CRP was associated with HCA. There was no significant association between HCA and anesthesia, mode of delivery, nor elevated I/T ratio. CONCLUSIONS: Maternal fever is associated with HCA. The HCA in conjunction with an elevated CRP can guide the duration of antimicrobial therapy in infants born to febrile mothers.