Maternal SARS-CoV-2, Placental Changes and Brain Injury in 2 Neonates.

Long-term neurodevelopmental sequelae are a potential concern in neonates following in utero exposure to severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2). We report 2 neonates born to SARS-CoV-2 positive mothers, who displayed early-onset (day 1) seizures, acquired microcephaly, and significant developmental delay over time. Sequential MRI showed severe parenchymal atrophy and cystic encephalomalacia. At birth, neither infant was SARS-CoV-2 positive (nasopharyngeal swab, reverse transcription polymerase chain reaction), but both had detectable SARS-CoV-2 antibodies and increased blood inflammatory markers. Placentas from both mothers showed SARS-CoV-2-nucleocapsid protein and spike glycoprotein 1 in the syncytiotrophoblast, fetal vascular malperfusion, and significantly increased inflammatory and oxidative stress markers pyrin domain containing 1 protein, macrophage inflammatory protein 1 ßη, stromal cell-derived factor 1, interleukin 13, and interleukin 10, whereas human chorionic gonadotropin was markedly decreased. One infant (case 1) experienced sudden unexpected infant death at 13 months of age. The deceased infant's brain showed evidence of SARS-CoV-2 by immunofluorescence, with colocalization of the nucleocapsid protein and spike glycoprotein around the nucleus as well as within the cytoplasm. The constellation of clinical findings, placental pathology, and immunohistochemical changes strongly suggests that second-trimester maternal SARS-CoV-2 infection with placentitis triggered an inflammatory response and oxidative stress injury to the fetoplacental unit that affected the fetal brain. The demonstration of SARS-CoV-2 in the deceased infant's brain also raises the possibility that SARS-CoV-2 infection of the fetal brain directly contributed to ongoing brain injury. In both infants, the neurologic findings at birth mimicked the presentation of hypoxic-ischemic encephalopathy of newborn and neurologic sequelae progressed well beyond the neonatal period.

First Locally Acquired Congenital Zika Syndrome Case in the United States: Neonatal Clinical Manifestations.

In the spring of 2017, a full-term infant with microcephaly was delivered in South Florida. During first trimester, the mother presented with fever, nausea, and vomiting. She reported no foreign travel for herself or her partner. The infant's neurologic, ophthalmologic, neuroradiologic, and audiologic findings were highly suggestive of congenital Zika syndrome (CZS), confirmed by IgM antibodies and plaque reduction neutralization test. New observations, including peripheral temporal retinal avascularity and peripapillary retinal nerve fiber layer thinning, are presented from this first known case of non-travel-associated CZS in the United States. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e93-e98.].

Scalp congenital hemangioma with associated high-output cardiac failure in a premature infant: Case report and review of literature.

Introduction Scalp congenital hemangiomas (CHs) are rare vascular malformations among infants; they can be associated with an array of complications, including cardiac and cosmetic issues. Here, we report the endovascular treatment of a premature infant with a suspected large right parietal scalp hemangioma and associated high-output cardiac failure. Case description A two-day-old female premature infant (29 weeks gestational age; 1330 g birth weight) was referred by the neonatologists to our department for consultation and potential treatment of a large right parietal CH causing abrupt hypotension and high-output cardiac failure. Doppler ultrasound imaging at bedside revealed areas of arterial-venous shunting from the scalp and the presence of a superior sagittal sinus waveform, consistent with intracranial venous drainage. To alleviate cardiac dysfunction secondary to this lesion, trans-arterial embolization via n-butyl cyanoacrylate (nBCA) glue and deployment of detachable coils was performed via umbilical artery to occlude the right superficial temporal and occipital artery branches supplying the CH. Following treatment, the infant continued to require ventilator management, vasopressor support, and correction of coagulopathy, but by post-operative day two, her condition improved remarkably and the mass size began decreasing. The patient was discharged after a relatively uncomplicated subsequent 2½-month course in the neonatal intensive care unit. Conclusion Endovascular therapy proved effective and safe in treating cardiac failure associated with scalp CH, despite potential complications associated with neuro-interventional surgery in premature infants. Appropriate consideration in this patient population should be given to factors including blood loss, contrast use, radiation exposure, operative time, and possible intra-/post-operative complications.

Perinatal Factors Associated with Cardiovascular Disease Risk among Preschool-Age Children in the United States: An Analysis of 1999-2008 NHANES Data.

We examined the relationships between selected perinatal and early infancy factors (maternal smoking during pregnancy, infant low birthweight, breastfeeding, and early introduction of solid foods [<6 months of age] and increased BMI [≥85th, ≥95th percentiles for age, sex]), waist circumference (WC), C-reactive protein (CRP), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, and decreased HDL cholesterol during early childhood. The population-based sample included 3,644 3-to-6-year-old Non-Hispanic White (NHW), Hispanic, and Non-Hispanic Black (NHB) children who participated in the 1999-2008 National Health and Nutrition Examination Surveys. Analysis showed that breastfeeding was significantly protective against early childhood obesity (OR 0.43, 95% CI, 0.27-0.69) and the highest quintile for WC (OR 0.58, 95% CI, 0.37-0.32) among NHW, and against the highest quintile of non-HDL cholesterol among NHB (OR 0.56, 95% CI, 0.32-0.98). Additionally, NHW children were significantly more likely to be obese (OR 2.22, 95% CI 1.30-3.78) and have higher CRP levels (OR 1.63, 95% CI, 1.05-2.51) if their mothers smoked during pregnancy. These results support the observation that breastfeeding may be protective against early childhood obesity while maternal smoking during pregnancy is a risk factor for obesity and increased CRP levels among NHW young children.

Estimated effect of prenatal cocaine exposure on examiner-rated behavior at age 7 years.

UNLABELLED: Prenatal cocaine exposure has been linked to increased child behavior difficulties in some studies but not others. OBJECTIVE: The primary aim was to estimate the relationship between in utero cocaine exposure and child behavioral functioning at age 7 years with ratings made by blinded examiners during a structured testing session. A second aim was to examine whether caregiver drug use and psychological problems might mediate suspected relationships between prenatal cocaine exposure and aspects of examiner-rated behavior. METHODS: 407 children (212 cocaine-exposed, 195 non-exposed) participating in the longitudinal Miami Prenatal Cocaine Study (MPCS) were rated with regard to their behavior during a neuropsychological assessment conducted at age 7 years. Raters were trained research psychometricians blinded to drug exposure status. Individual behavioral items were summarized and the cocaine-behavior relationship was estimated within the context of latent variable modeling, using Mplus software. RESULTS: Two latent variables, Behavioral Regulation and Sociability, were derived via exploratory latent structure analysis with promax rotation. Prenatal cocaine exposure, statistically controlling for child sex, test age, and prenatal exposure to alcohol, tobacco, and marijuana, was associated with Behavioral Regulation (estimated slope ß=-0.25; 95% CI=-0.48, -0.02; p=0.04) but not Sociability (estimated slope ß=-0.03; 95% CI=-0.26, 0.20; p=0.79). Neither postnatal drug use by caregivers nor the severity of their psychological problems at age 5 follow-up predicted levels of child Behavioral Regulation or Sociability at age 7 years (p>0.10). CONCLUSIONS: Examiner ratings of child behavior at age 7 revealed less optimal behavioral regulation for prenatally cocaine-exposed compared to non-exposed children, in contrast with what had been previously found from parent-report data. This evidence highlights the potential value of trained observers in assessing behavioral outcomes of children exposed in utero to drugs and other toxicants.

Estimated effects of in utero cocaine exposure on language development through early adolescence.

The potential longitudinal effects of prenatal cocaine exposure (PCE) on language functioning were estimated from early childhood through early adolescence in a large, well-retained urban sample of 451 full-term children (242 cocaine-exposed, 209 non-cocaine-exposed) participating in the Miami Prenatal Cocaine Study (MPCS). The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview, and toxicology assays of maternal and infant urine, and infant meconium. Age-appropriate versions of the Clinical Evaluation of Language Fundamentals (CELF) were used to measure total, expressive, and receptive language at ages 3, 5, and 12years. Longitudinal latent growth curve (LLGC) modeling of the data revealed an association between PCE (measured dichotomously as yes/no) and lower functioning in expressive and total language scores, after considering other sources of variation including child's age at testing, sex, prenatal exposure to alcohol, marijuana, and tobacco, and additional medical and social-demographic covariates. Analyses of level of PCE showed a gradient, i.e. dose-dependent, relationship between PCE level and expressive, receptive, and total language scores in the models controlling for age, child's sex, and other prenatal drug exposures. With additional covariate control these findings were most stable for the total language score. The evidence supports an inference about an enduring stable cocaine-specific effect on children's language abilities, with no effect on language growth over time in the longitudinal trajectory of language development.

Learning disabilities and intellectual functioning in school-aged children with prenatal cocaine exposure.

Risk for developing a learning disability (LD) or impaired intellectual functioning by age 7 was assessed in full-term children with prenatal cocaine exposure drawn from a cohort of 476 children born full term and enrolled prospectively at birth. Intellectual functioning was assessed using the Wechsler Intelligence Scale for Children-Third Edition (Wechsler, 1991) short form, and academic functioning was assessed using the Wechsler Individual Achievement Test (WIAT; Wechsler, 1993) Screener by examiners blind to exposure status. LDs were categorized based on ability-achievement discrepancy scores, using the regression-based predicted achievement method described in the WIAT manual. The sample in this report included 409 children (212 cocaine-exposed, 197 non-cocaine-exposed) from the birth cohort with available data. Cumulative incidence proportions and relative risk values were estimated using STATA software (Statacorp, 2003). No differences were found in the estimate of relative risk for impaired intellectual functioning (IQ below 70) between children with and without prenatal cocaine exposure (estimated relative risk = .95; 95% confidence interval [CI] = 0.65, 1.39; p = .79). The cocaine-exposed children had 2.8 times greater risk of developing a LD by age 7 than non-cocaine-exposed children (95% CI = 1.05, 7.67; p = .038; IQ >/= 70 cutoff). Results remained stable with adjustment for multiple child and caregiver covariates, suggesting that children with prenatal cocaine exposure are at increased risk for developing a learning disability by age 7 when compared to their non-cocaine-exposed peers.

Expressive and receptive language functioning in preschool children with prenatal cocaine exposure.

OBJECTIVE: To estimate the relationship between severity of prenatal cocaine exposure and expressive and receptive language skills in full-term, African American children at age 3 years. METHODS: Language was assessed at age 3 using the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P). The sample included 424 children (226 cocaine exposed, 198 non-cocaine exposed) who received preschool language assessments at age 3, drawn from a cohort of 476 children enrolled prospectively at birth. RESULTS: Structural equation modeling was used to regress expressive and receptive language as intercorrelated response variables on level of prenatal cocaine exposure, measured by a latent construct including maternal self-report of cocaine use and maternal/infant urine toxicology assays and infant meconium. Results indicated a.168 SD decrease in expressive language functioning for every unit increase in exposure level (95% CI = -.320, -.015; p =.031) after consideration for fetal growth and gestational age as correlated response variables. Receptive language was more modestly related to prenatal cocaine exposure and was not statistically significant. Results for expressive language remained stable with inclusion of the McCarthy general cognitive index as a response variable (expressive language beta = -.173, 95% CI = -.330, -.016; p =.031), and with adjustment for maternal age and prenatal exposures to alcohol, tobacco, and marijuana (expressive language beta = -.175, 95% CI = -.347, -.003; p =.046). Additional child and caregiver environmental variables assessed at age 3 were also evaluated in varying statistical models with similar results. CONCLUSION: The evidence from this study supports a gradient relationship between increased level of prenatal cocaine exposure and decreased expressive language functioning in preschool-aged cocaine-exposed children.

Severity of prenatal cocaine exposure and child language functioning through age seven years: a longitudinal latent growth curve analysis.

The current study estimates the longitudinal effects of severity of prenatal cocaine exposure on language functioning in an urban sample of full-term African-American children (200 cocaine-exposed, 176 noncocaine-exposed) through age 7 years. The Miami Prenatal Cocaine Study sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview and toxicology assays of maternal and infant urine and infant meconium. Language functioning was measured at ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals--Preschool (CELF-P) and at age 7 years using the Core Language Domain of the NEPSY: A Developmental Neuropsychological Assessment. Longitudinal latent growth curve analyses were used to examine two components of language functioning, a more stable aptitude for language performance and a time-varying trajectory of language development, across the three time points and their relationship to varying levels of prenatal cocaine exposure. Severity of prenatal cocaine exposure was characterized using a latent construct combining maternal self-report of cocaine use during pregnancy by trimesters and maternal and infant bioassays, allowing all available information to be taken into account. The association between severity of exposure and language functioning was examined within a model including factors for fetal growth, gestational age, and IQ as intercorrelated response variables and child's age, gender, and prenatal alcohol, tobacco, and marijuana exposure as covariates. Results indicated that greater severity of prenatal cocaine exposure was associated with greater deficits within the more stable aptitude for language performance (D = -0.071, 95% CI = -0.133, -0.009; p = 0.026). There was no relationship between severity of prenatal cocaine exposure and the time-varying trajectory of language development. The observed cocaine-associated deficit was independent of multiple alternative suspected sources of variation in language performance, including other potential responses to prenatal cocaine exposure, such as child's intellectual functioning, and other birth and postnatal influences, including language stimulation in the home environment.

Longitudinal influence of prenatal cocaine exposure on child language functioning.

The present study estimates the longitudinal effects of in utero cocaine exposure on language functioning at 3, 5 and 7 years of age in an urban sample of 443 full-term children (236 cocaine-exposed and 207 noncocaine-exposed) participating in the Miami Prenatal Cocaine Study. The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview and urine and meconium toxicology assays. Language functioning was measured at ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P) and at age 7 years using the Core Language Domain of the NEPSY: A Developmental Neuropsychological Assessment. Longitudinal Generalized Linear Model and Generalized Estimating Equations (GLM/GEE) analyses revealed an association between prenatal cocaine exposure and deficits in total language functioning after statistically controlling for child sex, visit age, prenatal exposure to alcohol, marijuana and tobacco and over 20 additional medical and sociodemographic covariates drawn from potentially confounding influences assessed at birth and follow-up visits (D=-0.17; 95% CI=-0.32, -0.03; P=.019). The link from prenatal cocaine exposure to later language deficits does not appear to be mediated by cocaine-associated deficits in birth weight, length or head circumference. Overall, the evidence tends to support an inference of a stable cocaine-specific effect on indicators of language functioning during early childhood through age 7 years.

Behavioral outcome of preschoolers exposed prenatally to cocaine: role of maternal behavioral health.

OBJECTIVE: To examine the impact of prenatal cocaine exposure and maternal behavioral health (recent drug use and psychological functioning) on child behavior at age 5 years. METHOD: In this longitudinal investigation, maternal report of child behavior was assessed using the Achenbach Child Behavior Checklist (CBCL) in 140 cocaine-exposed and 181 noncocaine-exposed (61 alcohol, tobacco, and/or marijuana-exposed, and 120 nondrug-exposed) low-income, African American children. Structural equation modeling was used to estimate suspected causal relationships between indicators of maternal behavioral health at 5-year follow-up, according to self-report on a modified Addiction Severity Index (ASI) and CBCL scores. RESULTS: Prenatal cocaine exposure was not related to child behavior at age 5. Recent maternal drug use and psychological functioning had relationships with CBCL Internalizing and Externalizing scores. However, when considered within a combined model, only maternal psychological functioning remained significant. CONCLUSIONS: Findings highlight the importance of maternal functioning in the behavioral outcome of children exposed prenatally to cocaine.