IMPORTANCE Preterm birth has previously been associated with increased risks of hypertension and diabetes, but not ischemic heart disease (IHD), in adulthood. The reasons for this lack of association with IHD despite associations with its risk factors have been elusive, but may be associated with methodologic issues, such as survivor bias, in prior studies.OBJECTIVE To determine whether preterm birth is associated with an increased risk of IHD in adulthood in a large population-based cohort. DESIGN, SETTING, AND PARTICIPANTSThis national, population-based cohort study included all 2 141 709 persons who were born as singleton live births in Sweden during 1973 to 1994. The data were analyzed in September 2018.EXPOSURES Gestational age at birth, identified from nationwide birth records in the Swedish Birth Registry. MAIN OUTCOMES AND MEASURESIschemic heart disease that was identified from nationwide inpatient and outpatient diagnoses through 2015 (maximum age, 43 years). A Cox regression was used to examine gestational age at birth in association with IHD in adulthood while adjusting for other perinatal and maternal factors. Cosibling analyses assessed for potential confounding by unmeasured shared familial factors. RESULTSOf 2 141 709 participants, 1 041 906 (48.6%) were female and there were 1921 persons (0.09%) who received a diagnosis of IHD in 30.9 million person-years of follow-up. Gestational age at birth was inversely associated with IHD risk in adulthood. At ages 30 to 43 years, adjusted hazard ratios for IHD associated with preterm (gestational age <37 weeks) and early-term birth (37-38 weeks) were 1.53 (95% CI, 1.20-1.94) and 1.19 (1.01-1.40), respectively, compared with full-term birth (39-41 weeks). Preterm-born women had lower IHD incidence than preterm-born men (15.16 vs 22.00 per 100 000 person-years) but had a higher adjusted hazard ratio (1.93; 95% CI, 1.28-2.90 vs 1.37; 95% CI, 1.01-1.84). These associations did not appear to be explained by shared genetic or environmental factors in families. CONCLUSIONS AND RELEVANCEIn this large national cohort, preterm and early-term birth were associated with an increased IHD risk in adulthood. Persons born prematurely need early evaluation and preventive actions to reduce the risk of IHD.

• On the basis of observational studies (level C), preterm birth is a leading cause of neurodevelopmental disabilities in children, and the degree of neurodevelopmental disability is inversely correlated with gestational age at birth. When comparing performance of preterm children to developmental norms, “corrected age” or age from due date rather than birth date should be used for the first 24 to 36 months. • On the basis of observational studies (level C), clinicians should pay specific attention to sensory function in children born preterm because the incidence of visual and hearing impairments is higher in preterm than term children. Due to the elevated risk of cognitive and behavioral disabilities, clinicians caring for children born preterm should be vigilant when performing developmental assessments to improve outcomes. • On the basis of observational studies (level C), early identification of developmental delays allows for referral to therapeutic services, and children referred for early intervention are more likely to make gains in developmental milestones.

The incidence of diagnosis of BPD decreased significantly between 1993 and 2006. In well-controlled models, birth hospitalization charges for these patients rose during the same period. Less invasive ventilatory support may improve respiratory outcomes of VLBW neonates.

Objective To examine the relationships between growth (birth to age 2 years) and developmental outcomes in children born with very low birthweight (VLBW). Design Motor and mental development in children born with VLBW were regressed on anthropometric measurements at birth, 9 months and 2 years using multivariable regression. Setting The Early Childhood Longitudinal Study—Birth Cohort, a longitudinal cohort, community sample, designed to be representative of children born across the USA. Patients 950 children born with VLBW (<1500 g). Main Outcome Measures Motor and cognitive scores on the Bayley Scales at 9 months and 24 months chronological age. Results A high proportion of children exhibited poor growth, with length-for-age z-scores <−2 (ie, stunting) in 21.3% of children at 9 months (adjusted for prematurity) and 34.2% of children at 2 years. Compared with children having z-scores >−2, children with growth shortfalls in head circumference, length and weight had a higher adjusted OR (aOR) of low Bayley motor scores at 9 months and 2 years (aOR ranging from 1.8 to 3.3, all p<0.05), while low Bayley cognitive scores were predicted by 9-month deficits in length and weight (aOR 2.0 and 2.4, respectively, both p<0.01) and 2-year deficits in length and head circumference (aOR 2.9 and 2.8, both p<0.05). Conclusion Anthropometric measures of growth were linked to current and future neurodevelopmental outcomes in children born with VLBW. While careful length measures may be a particularly useful marker, deficits in all anthropometric measures were risk factors for developmental delays.

Objective To determine clinical characteristics, demographics, and short-term outcomes of neonates diagnosed with fetomaternal hemorrhage (FMH). Design We analyzed the Nationwide Inpatient Sample, 1993-2008. Singleton births diagnosed with FMH were identified by ICD-9 code 762.3. Descriptive, univariate, and multivariable regression analyses were performed to determine the national annual incidence of FMH over time as well as demographics and clinical characteristics of neonates with FMH. Results Fetomaternal hemorrhage was identified in 12,116 singleton births. Newborns with FMH required high intensity of care: 26.3% received mechanical ventilation, 22.4% received blood product transfusion, and 27.8% underwent central line placement. Preterm birth (OR 3.7), placental abruption (OR 9.8) and umbilical cord anomaly (OR 11.4) were risk factors for FMH. Higher patient income was associated with increased likelihood of FMH diagnosis (OR 1.2), and whites were more likely to be diagnosed than ethnic minorities (OR 1.9). There was reduced frequency of diagnosis in the Southern United States (OR 0.8 versus the Northeastern United States). Conclusions Diagnosis of FMH is associated with significant morbidity as well as regional, socioeconomic, and racial disparity. Further study is needed to distinguish between diagnostic coding bias and true epidemiology of the disease. This is the first report of socioeconomic and racial/ethnic disparities in FMH, which may represent disparities in detection that require national attention.

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In the United States each year, more than 300,000 infants are admitted to neonatal intensive care units (NICU) where they are exposed to a chemical-intensive hospital environment during a developmentally vulnerable period. Although multiple studies have demonstrated elevated phthalate biomarkers in NICU patients, specific sources of NICU-based phthalate exposure have not been identified.

IMPORTANCEA targeted genomic sequencing platform focused on diseases presenting in the first year of life may minimize financial and ethical challenges associated with rapid whole-genomic sequencing.OBJECTIVE To report interim variants and associated interpretations of an ongoing study comparing rapid whole-genomic sequencing with a novel targeted genomic platform composed of 1722 actionable genes targeting disorders presenting in infancy. DESIGN, SETTING, AND PARTICIPANTSThe Genomic Medicine in Ill Neonates and Infants (GEMINI) study is a prospective, multicenter clinical trial with projected enrollment of 400 patients. The study is being conducted at 6 US hospitals. Hospitalized infants younger than 1 year of age suspected of having a genetic disorder are eligible. Results of the first 113 patients enrolled are reported here. Patient recruitment began in July 2019, and the interim analysis of enrolled patients occurred from March to June 2020.INTERVENTIONS Patient (proband) and parents (trios, when available) were tested simultaneously on both genomic platforms. Each laboratory performed its own phenotypically driven interpretation and was blinded to other results. MAIN OUTCOMES AND MEASURESVariants were classified according to the American College of Medical Genetics and Genomics standards of pathogenic (P), likely pathogenic (LP), or variants of unknown significance (VUS). Chromosomal and structural variations were reported by rapid whole-genomic sequencing.RESULTS Gestational age of 113 patients ranged from 23 to 40 weeks and postmenstrual age from 27 to 83 weeks. Sixty-seven patients (59%) were male. Diagnostic and/or VUS were returned for 51 patients (45%), while 62 (55%) had negative results. Results were concordant between platforms in 83 patients (73%). Thirty-seven patients (33%) were found to have a P/LP variant by 2 or both platforms and 14 (12%) had a VUS possibly related to phenotype. The median day of life at diagnosis was 22 days (range, 3-313 days). Significant alterations in clinical care occurred in 29 infants (78%) with a P/LP variant. Incidental findings were reported in 7 trios. Of 51 positive cases, 34 (67%) differed in the reported result because of technical limitations of the targeted platform, interpretation of the variant, filtering discrepancies, or multiple causes. CONCLUSIONS AND RELEVANCEAs comprehensive genetic testing becomes more routine, these data highlight the critically important variant detection capabilities of existing genomic sequencing technologies and the significant limitations that must be better understood.