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Objective: To evaluate associations between change in weight z score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm., Study Design: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n = 1400). Growth during infancy was calculated as change in weight z score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z score <-1.67; very high weight gain was a change in weight z score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z score and neurodevelopmental outcomes., Results: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% CI: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% CI: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% CI: 3.99, 9.66) but not with neurodevelopmental outcomes., Conclusions: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments., Competing Interests: Declaration of Competing Interest Research reported in this publication was supported by the Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health, under Award Numbers U2COD023375 (B. Smith, PI), U24OD023382 (Data Analysis Center), U24OD023319 (R. Gershon, PI) with co-funding from the Office of Behavioral and Social Science Research, UH3OD023348 (T M. O'Shea, PI; R.C. Fry, PI), 2UG1HD027904 (J. Maron, PI), UH3OD023320 (JL Aschner, PI), UH3OD023347 (BM Lester, PI), UG3OD035513 (A. Stroustrup, PI). The authors declare no conflicts of interest. The sponsor, National Institutes of Health (NIH), participated in the overall design and implementation of the ECHO Program, which was funded as a cooperative agreement between NIH and grant awardees. The sponsor approved the Steering Committee-developed ECHO protocol and its amendments including COVID-19 measures. The sponsor had no access to the central database, which was housed at the ECHO Data Analysis Center. Data management and site monitoring were performed by the ECHO Data Analysis Center and Coordinating Center. All analyses for scientific publication were performed by the study statistician, independently of the sponsor. The lead author wrote all drafts of the manuscript and made revisions based on co-authors and the ECHO Publication Committee (a subcommittee of the ECHO Operations Committee) feedback without input from the sponsor. The study sponsor did not review nor approve the manuscript for submission to the journal., (Copyright © 2024 Elsevier Inc. All rights reserved.)

How did vocal language originate? Before trying to determine how referential vocabulary or syntax may have arisen, it is critical to explain how ancient hominins began to produce vocalization flexibly, without binding to emotions or functions. A crucial factor in the vocal communicative split of hominins from the ape background may thus have been copious, functionally flexible vocalization, starting in infancy and continuing throughout life, long before there were more advanced linguistic features such as referential vocabulary. 2-3 month-old modern human infants produce "protophones", including at least three types of functionally flexible non-cry precursors to speech rarely reported in other ape infants. But how early in life do protophones actually appear? We report that the most common protophone types emerge abundantly as early as vocalization can be observed in infancy, in preterm infants still in neonatal intensive care. Contrary to the expectation that cries are the predominant vocalizations of infancy, our all-day recordings showed that protophones occurred far more frequently than cries in both preterm and full-term infants. Protophones were not limited to interactive circumstances, but also occurred at high rates when infants were alone, indicating an endogenous inclination to vocalize exploratorily, perhaps the most fundamental capacity underlying vocal language.

Objectives: To determine the effects of human milk and social/environmental disparities on developmental outcomes of infants born preterm cared for in a single-family room (SFR) neonatal intensive care unit (NICU)., Study Design: Outcomes were compared between infants weighing ?1250 g cared for in an open-bay NICU (1/2007-8/2009) (n?=?394) and an SFR NICU (1/2010-12/2011) (n?=?297). Human milk provision at 1 week, 4 weeks and discharge, and 4 week volume (mL/kg/day) were analyzed. At 18-24 months of age, the Bayley III was administered. Group differences were evaluated and multiple linear regression analyses were run., Results: Infants cared for in the SFR NICU had higher Bayley III cognitive and language scores, higher rates of human milk provision at 1 and 4 weeks, and higher human milk volume at 4 weeks. In adjusted regression models, the SFR NICU was associated with a 2.55-point increase in Bayley cognitive scores and 3.70-point increase in language scores. Every 10?mL/kg/day increase of human milk at 4 weeks was independently associated with increases in Bayley cognitive, language, and motor scores (0.29, 0.34, and 0.24, respectively). Medicaid was associated with decreased cognitive (?4.11) and language (?3.26) scores, and low maternal education and non-white race with decreased language scores (?4.7 and ?5.8, respectively). Separate models by insurance status suggest there are differential benefits from SFR NICU and human milk between infants with Medicaid and private insurance., Conclusions: Infants born preterm cared for in the SFR NICU have higher Bayley language and cognitive scores and receive more human milk. Independent effects on outcomes were derived from SFR NICU, provision of human milk, and social and environmental factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Adults born preterm at very low birth weight (VLBW; <1500 g) have higher blood pressure than those born at term. It is not known whether all VLBW adults are at risk or whether higher blood pressure could be attributed to some of the specific conditions underlying or accompanying preterm birth. To identify possible risk or protective factors, we combined individual-level data from 9 cohorts that measured blood pressure in young adults born at VLBW or with a more stringent birth weight criterion. In the absence of major heterogeneity, we performed linear regression analysis in our pooled sample of 1571 adults born at VLBW and 777 controls. Adults born at VLBW had 3.4 mm Hg (95% confidence interval, 2.2-4.6) higher systolic and 2.1 mm Hg (95% confidence interval, 1.3-3.0) higher diastolic pressure, with adjustment for age, sex, and cohort. The difference in systolic pressure was present in men (1.8 mm Hg; 95% confidence interval, 0.1-3.5) but was stronger in women (4.7 mm Hg; 95% confidence interval, 3.2-6.3). Among the VLBW group, blood pressure was unrelated to gestational age, maternal smoking, multiple pregnancy, retinopathy of prematurity, or bronchopulmonary dysplasia. Blood pressure was higher than that of controls among VLBW adults unexposed to maternal preeclampsia. Among those exposed, it was even higher, especially if born appropriate for gestational age. In conclusion, although female sex and maternal preeclampsia are additional risk factors, the risk of higher blood pressure is not limited to any etiologic subgroup of VLBW adults, arguing for vigilance in early detection of high blood pressure in all these individuals., (© 2016 American Heart Association, Inc.)

Objective: To evaluate characteristics of unimpaired outcome in extremely low-birth-weight (ELBW) survivors., Study Design: ELBW infants (n=714) with 30 months' assessments were analyzed. Logistic regression was used to develop a model for the binary outcome of unimpaired versus impaired outcome., Result: Thirty-three percent of infants had an unimpaired outcome. Seventeen percent of ELBW survivors had a Bayley II Mental Developmental Index score of ≥ 101 and 2% had a score of ≥ 116. Female gender, use of antenatal steroids (ANS), maternal education ≥ high school and the absence of major neonatal morbidities were independent predictors of unimpaired outcome. The likelihood of an unimpaired outcome in the presence of major neonatal morbidities was higher in infants exposed to ANS., Conclusion: The majority of unimpaired ELBW survivors had cognitive scores shifted toward the lower end of the normal distribution. Exposure to ANS was associated with higher likelihood of an unimpaired outcome in infants with major neonatal morbidities.

Objective: Transfer of clinically stable infants to level I and II nurseries alleviates demands on NICUs and allows better use of beds and resources. This study compared growth, neurodevelopmental impairments, postdischarge rehospitalization and deaths, and compliance for follow-up assessment at 18 to 22 months' corrected age of extremely low birth weight infants who transferred to level I and II nurseries with those who continued to receive care to discharge in a NICU., Methods: A retrospective analysis of prospectively collected data from the National Institute of Child Health and Human Development Neonatal Research Network was performed. Between January 1998 and June 2002, 4896 infants born with birth weights of 401 to 1000 g and cared for in 19 National Institute of Child Health and Human Development Neonatal Research Network centers were included. The sample consisted of 4392 survivors who received continuing care in the NICU to discharge home and 504 infants who were transferred to level I and II nurseries before discharge home. Demographics, perinatal characteristics, growth, and neurodevelopmental impairments were compared. Bivariate and logistic regression analyses were performed., Results: Transfer of infants to level I and II nurseries was associated significantly with white race, private insurance, outborn status, and lower neonatal morbidities and compliance for follow-up compared with the NICU group. After adjusting for known covariates, transfer to level I and II nurseries was not associated with neurodevelopmental impairments or death; however, it was associated with increased postdischarge rehospitalization., Conclusions: Extremely low birth weight infants who are transferred to level I and II nurseries have similar growth and neurodevelopmental outcomes to infants who are discharged from a NICU. They are, however, more likely to be readmitted to the hospital and are less compliant for follow-up. Establishment of consistent guidelines for comprehensive discharge planning for level I and II nurseries may improve follow-up compliance and reduce rehospitalization rates among these infants who are transferred.

Objective: To determine neonatal outcome at 7 months of corrected age in very low birth weight (VLBW) infants with placental chorioamnionitis., Methods: We conducted a cohort study of 287 VLBW infants delivered as a result of preterm premature rupture of membranes (PROM) or preterm labor. Control subjects (n = 123) had placentas with absent umbilical cord inflammation and absent or low-grade membrane inflammation. Case subjects (n = 164) had moderate membrane inflammation or any umbilical cord inflammation. Neonatal and 7-month outcomes were compared. A power analysis showed that 98 total subjects were needed to reject the two-sided null hypothesis with a difference in mean Bayley index scores of at least 8., Results: Infants in the study group had significantly more preterm PROM, antenatal antibiotics, lower birth weight, lower gestational age, longer duration of ruptured membranes, and clinical chorioamnionitis. Intraventricular hemorrhage occurred more commonly in infants with placentas demonstrating chorioamnionitis (relative risk = 1.6, 95% confidence interval 1.1, 2.4, P =.013). One hundred sixty-seven (69%) of the 243 surviving infants had 7-month follow-up. There was no difference between cases and controls in mean Bayley mental developmental index (93 compared with 90, P =.25), psychomotor developmental index (89 compared with 90, P =.68), or in the number of infants that were developmentally delayed., Conclusion: Despite a higher frequency of intraventricular hemorrhage, no difference in developmental scores was detected at 7 months of corrected age in VLBW infants with histologic chorioamnionitis.

Objective: The purpose of this study was to explore the development of adiposity in macrosomic and normosomic infants of mothers with gestational diabetes mellitus (GDM) and control subjects between birth and age 1 year, and assess its relation to maternal prenatal factors and neonatal factors., Research Design and Methods: This was a prospective observational study of 192 infants, including 47 large-for-gestational-age (LGA) infants of GDM mothers, 47 appropriate-for-gestational-age (AGA) infants of GDM mothers, 55 LGA control infants, and 44 AGA control infants who were evaluated at birth and age 1 year. Maternal prenatal and pregnancy anthropometric measurements were recorded. Multiple infant anthropometric measurements, including skinfold thicknesses, were obtained at birth and age 1 year. Regression models were run to detect the independent effects of various maternal and infant factors on 1-year child adiposity, adjusting for their effects at birth., Results: LGA infants of GDM mothers had a higher BMI, waist circumference, and abdominal skinfold at age 1 year compared with all other study groups. Among infants of GDM mothers, the mean 2-h postprandial glucose value for the second and third trimester correlated with waist circumference (r = 0.28, P < 0.04) and subscapular skinfold (r = 0.37, P < 0.007), and correlated marginally with 1-year sum of four skinfolds. Among infants of GDM mothers, a regression of 1-year sum of four skinfolds was significantly related to maternal prepregnancy weight after controlling for sum of skinfolds at birth. For control infants, the maternal glucose screen value was significantly associated with 1-year sum of skinfolds adjusted for the birth sum of skinfolds., Conclusions: We concluded that macrosomic infants of GDM mothers have unique patterns of adiposity that are present at birth and persist at age 1 year. Further, we concluded that maternal factors, including adiposity and intrauterine fuel environment, influence the presence and distribution of adiposity for both infants of GDM mothers and control infants.

Objectives: Low-dose indomethacin has been shown to prevent intraventricular hemorrhage (IVH) in very low birth weight neonates, and long-term neurodevelopmental follow-up data are needed to validate this intervention. We hypothesized that the early administration of low-dose indomethacin would not be associated with adverse cognitive outcome at 36 months' corrected age (CA)., Methods: We enrolled 431 neonates of 600 to 1250 g birth weight with no IVH at 6 to 12 hours in a randomized, prospective trial to determine whether low-dose indomethacin would prevent IVH. A priori, neurodevelopmental follow-up examinations, including the Stanford-Binet Intelligence Scale and Peabody Picture Vocabulary Test-Revised, and standard neurologic examinations were planned at 36 months' CA., Results: Three hundred eighty-four of the 431 infants survived (192 [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants receiving saline), and 343 (89%) children were examined at 36 months' CA. Thirteen (8%) of the 166 infants who received indomethacin and 14 (8%) of 167 infants receiving the placebo were found to have cerebral palsy. There were no differences in the incidence of deafness or blindness between the two groups. For the 248 English-monolingual children for whom IQ data follow, the mean gestational age was significantly younger for the infants who received indomethacin than for those who received the placebo. None of the 115 infants who received indomethacin was found to have ventriculomegaly on cranial ultrasound at term, compared with 5 of 110 infants who received the placebo. The mean +/- SD Stanford-Binet IQ score for the 126 English-monolingual children who had received indomethacin was 89.6 +/- 18.92, compared with 85.0 +/- 20.79 for the 122 English-monolingual children who had received the placebo. Although maternal education was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no difference in educational levels between mothers of the infants receiving indomethacin and the placebo., Conclusions: Indomethacin administered at 6 to 12 hours as prophylaxis against IVH in very low birth weight infants does not result in adverse cognitive or motor outcomes at 36 months' CA.

Objective: To determine whether the "goodness of fit" between infant cry characteristics and the mother's perception of the cry is related to developmental outcome at 18 months of age., Design: This was a prospective, longitudinal study from birth to 18 months performed in a blinded manner., Setting: The study was conducted in a maternity hospital, including normal and special care nurseries and a laboratory for developmental follow-up., Patients: The 121 term and preterm infants and their mothers were selected to meet medical criteria., Measurement: Acoustic analysis of 1-month infant cry and the mother's perception of the same cry was used to divide subjects into four groups representing matches and mismatches between infant cry characteristics and maternal cry perception. Primary outcome measures of cognitive, language, motor, and neurologic outcome were administered at 18 months. Caretaking environment measures were also recorded., Results: Statistically significant (P < .05) findings showed that matched groups scored higher on measures of language and cognitive performance than infants in the mismatch groups, with a particular advantage for infants in the matched group in which mothers accurately perceived the higher-pitched cries of their infants. There were no differences between the groups in biologic or sociodemographic factors. Group differences were observed in social support and maternal self-esteem., Conclusions: Matches and mismatches between infant cry characteristics at 1 month and the mother's perception of the cry are related to cognitive and language outcome at 18 months in term and preterm infants. This relation is probably due to transactional processes in which developmental outcome is affected by the clarity of the infants' signals and by the ability of the mother to accurately perceive her infant's signals. The mother's ability to read her infant's cues may be affected by factors such as social support and self-esteem.

The effect of maternal and environmental factors on the developmental outcome of infants with low medical risk born to adolescent and non-adolescent, primiparous, Caucasian mothers was studied. Twenty-one were adolescent mothers (less than or equal to 17 years of age) and 21 were non-adolescent (21-29 years of age). Assessment of child care support, life stress, and home environment were carried out at 4 months. Infants were examined at 8 months, and child care support and life stress were reassessed. Adolescent mothers reported less child care support at both 4 and 8 months and more life stress at 8 months than non-adolescent mothers. Adolescent mothers were also found to be less responsive, used restriction and punishment more often, and were less involved with their infants during the home observation. Infants of adolescent mothers had lower Bayley Mental Development Indices at 8 months. A theoretical model, whereby the mother's age, education, and socioeconomic status (SES) were conducive to less optimal child care support and life stress, which in turn affected the infant's cognitive status, was supported by this data. Thus, within a low medical risk population, we have documented the significant role of maternal and environmental factors in determining the infant's cognitive status.

The growth pattern and neurologic and developmental performance of 21 preterm infants small for gestational age and 20 preterm infants appropriate for gestational age (birth weight less than 1500 gm) were prospectively studied. The two groups had comparable birth weight, sex, perinatal morbidities, and socioeconomic status. All infants with congenital anomalies or genetic defects were excluded. Nineteen of 21 SGA (90%) and 16 of 20 AGA (80%) infants born in 1975 or 1976 were evaluated in our follow-up program until 5 years of age. At 1 year of age, the weights and lengths of the SGA infants were comparable to those of their AGA counterparts; AGA infants were significantly heavier, however, at 2, 3, 4, and 5 years of age. In addition, AGA infants were significantly taller at 2, 3, and 5 years. Neurologic evaluation of 5 years showed a comparable rate of major abnormalities between the SGA (15%) and AGA (12%) children. Minor neurologic abnormalities were present in 26% of SGA and 12% of AGA children. Linear-regression analysis demonstrated a positive relationship between socioeconomic status and developmental outcome for both SGA and AGA children at 5 years of age. Although SGA infants scored significantly lower in developmental performance at 9 months through 3 years of age, at 4 to 5 years of age this difference was no longer observed. These observations indicate the importance of long-term follow-up.

The changing patterns of neurologic and developmental functioning between 1 and 7 years of age were studied in very low-birth-weight infants (birth weight less than or equal to 1,500 g). Subjects included 42 infants born in 1975 who were followed for 7 years. Based on the 1-year neurologic assessment, 22 infants were classified as normal, 12 as suspect, and eight as abnormal. The three groups did not differ in birth weight, gestational age, sex, or Hollingshead socioeconomic status (SES) score. The neurologic findings at 7 years of age were significantly related to the neurologic examination findings at 1 year of age. Seventy-seven percent of the normal group, 58% of the suspect group, and 100% of the abnormal group remained in the same neurologic category at 7 years of age. Children in the abnormal group had the greatest improvement in cognitive functioning between 1 and 7 years of age but did not achieve the IQ level of children in the normal group. Forty-five percent of the normal group, 75% of the suspect group, and 100% of the abnormal group had poor visual-motor integration. Fifty-eight percent of the suspect group and 87% of the abnormal group were reading below age level. Of the total sample, 54% required special education or resource help at 7 years of age, and the three groups differed significantly in their need for a special educational plan (P less than .05). These data indicate that a neurologic classification at 1 year of age provides a guide for monitoring very low-birth-weight infants and can be helpful in alerting school personnel to potential needs.