Timing of Systemic Steroids and Neurodevelopmental Outcomes in Infants < 29 Weeks Gestation

Objective: To determine the association between postnatal age (PNA) at first administration of systemic postnatal steroids (sPNS) for bronchopulmonary dysplasia (BPD) and mortality or significant neurodevelopmental impairment (sNDI) at 18−24 months corrected age (CA) in infants < 29 weeks' gestation. Methods: Data from the Canadian Neonatal Network and Canadian Neonatal Follow-up Network databases were used to conduct this retrospective cohort study. Infants exposed to sPNS for BPD after the 1st week of age were included and categorized into 8 groups based on the postnatal week of the exposure. The primary outcome was a composite of mortality or sNDI. A multivariable logistic regression model adjusting for potential confounders was used to determine the association between the sPNS and ND outcomes. Results: Of the 10,448 eligible infants, follow-up data were available for 6200 (59.3%) infants. The proportion of infants at first sPNS administration was: 8%, 17.5%, 23.1%, 18.7%, 12.6%, 8.3%, 5.8%, and 6% in the 2nd, 3rd, 4th, 5th, 6th, 7th, 8−9th, and ≥10th week of PNA respectively. No significant association between the timing of sPNS administration and the composite outcome of mortality or sNDI was observed. The odds of sNDI and Bayley-III motor composite < 70 increased by 1.5% (95% CI 0.4, 2.9%) and 2.6% (95% CI 0.9, 4.4%), respectively, with each one-week delay in the age of initiation of sPNS. Conclusions: No significant association was observed between the composite outcome of mortality or sNDI and PNA of sPNS. Among survivors, each week's delay in initiation of sPNS may increase the odds of sNDI and motor delay.

Follow-up care of the extremely preterm infant after discharge from the neonatal intensive care unit.

The survival of babies born extremely preterm (EP, <28 weeks gestation) has improved over time, and many have good outcomes and quality of life. They remain at risk for health issues, including neurosensory and neurodevelopmental difficulties requiring monitoring by primary physicians, paediatricians, and specialty clinics. This statement reviews potential medical and neurodevelopmental consequences for EP infants in the first 2 years after discharge and provides strategies for counselling, early detection, and intervention. EP-related conditions to assess for early include bronchopulmonary dysplasia or respiratory morbidity, feeding and growth concerns, neurosensory development (vision and hearing), cerebral palsy, and autism spectrum disorder. Correction for gestational age should be used for growth and development until 36 months of age. Integral to quality care of the child born EP is attention to the emotional well-being of parents and caregivers.

Association of inotrope use with neurodevelopmental outcomes in infants <29 weeks gestation: a retrospective cohort study.

OBJECTIVE: The primary objective was to compare neurodevelopmental (ND) outcomes at 18-24 months in preterm infants <29 weeks gestational age (GA) who received versus those who did not receive inotropes in the first week of life. The secondary objective was to assess ND outcomes according to the duration of inotropic support in the first week of life (≤3 or >3 days). STUDY DESIGN: Retrospective population-based cohort study of preterm infants <29 weeks GA admitted to participating neonatal intensive care units (NICUs) of the Canadian Neonatal Network (CNN) from January 2010 to September 2011 with follow-up data available at 18-24 months. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Long-term outcomes were categorized as neurodevelopmental impairment (NDI) and significant neurodevelopmental impairment (sNDI), and effect modification due to other neonatal morbidities including receipt of antenatal steroids, GA, small for gestational age (SGA) status, sex, score for neonatal acute physiology (SNAP-II) >20, postnatal steroids, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) grade ≥3/periventricular leukomalacia (PVL), early- and late-onset sepsis, retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC) was assessed. Maternal and infant demographic characteristics and short- and long-term outcomes were compared using Pearson's Chi-square test for categorical variables and Student's t-test or the Wilcoxon rank test for continuous variables. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated using multivariable regression analysis. RESULTS: Of the 491 (18.7%) eligible preterm infants who received inotropes during the first week of life, 314 (64%) survived to NICU discharge and 245 (78%) had ND outcome data available. A total of 1775 eligible preterm infants did not receive inotropes in the first week of life; 1647 (92.7%) survived to NICU discharge and 1149 (70%) had ND outcome data. Maternal and infant characteristics associated with infants receiving inotropes included: younger maternal age, clinical chorioamnionitis, no antenatal steroids, outborn, lower GA, BW and Apgar scores at both one and five minutes; and higher SNAP-II scores (p < .05). Infants who received inotropes in the first week of life were more likely to be require postnatal steroids, had higher rates of BPD, IVH grade ≥3/PVL, early- and late-onset sepsis, ROP, NEC and mortality (p < .05). Infants who received inotropes in the first week of life also had higher rates of sensorineural or mixed hearing loss with an AOR (95% CI) of 1.99 (1.13, 3.49). After adjusting for confounding variables, there was no difference in the risk of NDI or sNDI between infants who did and did not receive inotropes in the first week of life. Of the infants with neurodevelopmental outcome data available, 186 received inotropes for ≤3 days and 59 for >3 days. After adjusting for confounding variables there was no difference in the risk of NDI or sNDI. Infants who received inotropes for >3 days were more likely to have lower BSID-III cognitive [AOR 2.43 95% CI (1.03, 5.76)] and motor scores <85 [AOR 2.38 95% CI (1.07, 5.30)] respectively. CONCLUSIONS: In this large, population-based cohort, infants who received inotropes in the first week of life were at increased risk for sensorineural or mixed hearing loss. There was no difference in NDI or sNDI after adjusting for confounding variables. A longer duration of inotrope use in the first week of life was associated with lower BSID-III cognitive and motor scores, but no difference in overall NDI or sNDI.

Lower Maternal Chronic Physiological Stress and Better Child Behavior at 18 Months: Follow-Up of a Cluster Randomized Trial of Neonatal Intensive Care Unit Family Integrated Care.

OBJECTIVE: To assess whether Family Integrated Care (FICare) in the neonatal intensive care unit improves maternal chronic physiological stress and child behavior at 18 months of corrected age for infants born preterm. STUDY DESIGN: Follow-up of a multicenter, prospective cluster-randomized controlled trial comparing FICare and standard care of children born at <33 weeks of gestation and parents, stratified by tertiary neonatal intensive care units, across Canada. Primary outcomes at 18 months of corrected age were maternal stress hormones (cortisol, ie, hair cumulative cortisol [HCC], dehydroepiandrosterone [DHEA]) assayed from hair samples. Secondary outcomes included maternal reports of parenting stress, child behaviors (Internalizing, Externalizing, Dysregulation), and observer-rated caregiving behaviors. Outcomes were analyzed using multilevel modeling. RESULTS: We included 126 mother-child dyads from 12 sites (6 FICare sites, n = 83; 6 standard care sites, n = 43). FICare intervention significantly lowered maternal physiological stress as indicated by HCC (B = -0.22 [-0.41, -0.04]) and cortisol/DHEA ratio (B = -0.25 [-0.48, -0.02]), but not DHEA (B = 0.01 [-0.11, 0.14]). Enrollment in FICare led to lower child Internalizing (B = -0.93 [-2.33, 0.02]) and Externalizing behavior T scores (B = -0.91 [-2.25, -0.01]) via improvements to maternal HCC (mediation). FICare buffered the negative effects of high maternal HCC on child Dysregulation T scores (B = -11.40 [-23.01, 0.21]; moderation). For mothers reporting high parenting stress at 18 months, FICare was related to lower Dysregulation T scores via maternal HCC; moderated mediation = -0.17 (-0.41, -0.01). CONCLUSIONS: FICare has long-term beneficial effects for mother and child, attenuating maternal chronic physiological stress, and improving child behavior in toddlerhood. CLINICAL TRIAL REGISTRATION: NCT01852695.

Fetal myelomeningocele surgery: Only treating the tip of the iceberg.

OBJECTIVE: Fetal myelomeningocele (fMMC) surgery improves infant outcomes when compared with postnatal surgery. Surgical selection criteria and the option of pregnancy termination, however, limit the number of cases that are eligible for prenatal surgery. We aimed to quantify what proportion of cases could ultimately benefit from fetal therapy. METHODS: We retrospectively reviewed all cases of fMMC referred to a large tertiary care center over a 10-year period and assessed their eligibility for fetal surgery, pregnancy termination rates, and actual uptake of the surgery. RESULTS: Of 158 cases, 67 (42%) were ineligible for fetal surgery based on surgical exclusion criteria. Eleven fetuses (7%) had chromosomal anomalies, 10 of which (91%) had other anomalies on ultrasound. Thirty-four patients had a combination of maternal and fetal contraindications. Of the remaining 91 eligible cases (58%), 45 (49%) pregnancies were terminated, leaving only 46 (29% of initial 158 cases) as potential candidates for fetal repair. Actual uptake of fetal surgery was 15% (n = 14 of 91), but this increased after a national program was started. CONCLUSION: Only a minority of fMMC cases will ultimately undergo fetal surgery. These numbers support the centralization of care in expert centers.

Neonatal Factors Associated with a Good Neurodevelopmental Outcome in Very Preterm Infants.

Objective This study aims to examine the association between the absence of neonatal comorbidities, as well as the presence of indicators of clinical progress with good neurodevelopmental (ND) outcomes, at 18 months corrected age in a national cohort of preterm infants of < 29 weeks' gestation. Design Study subjects included preterm infants (< 29 weeks' gestation) born in 2010 and 2011. Univariate analyses were conducted and regression estimates were calculated for variables where odds of a good ND outcome, composite scores ≥ 100 in three domains (cognitive, language, and motor) in the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley-III), were estimated. Results In total, 2,069 infants were included in the analyses. For all three domains evaluated on the Bayley-III, cognition, language, motor, respectively, the absence of three major morbidities was associated with a score ≥ 100: bronchopulmonary dysplasia, necrotizing enterocolitis, and severe neurological injury. Less time spent on positive pressure support and on total parenteral nutrition administration were associated with a positive motor outcome and showed a positive trend for both cognition and language scores. Conclusion The absence of neonatal comorbidities was associated with good ND outcome. Less time spent on positive pressure support and parenteral nutrition may also contribute to a good ND outcome.