Meera Sankar, MD

To examine whether hydrocortisone (HC) modified the relationship of patent ductus arteriosus (PDA) to outcomes among infants born extremely preterm and enrolled in the NICHD Neonatal Research Network (NRN) HC trial.This was a post hoc secondary analysis of infants born < 30 weeks' gestation and enrolled in the NRN HC Trial. The primary outcome was moderate to severe bronchopulmonary dysplasia (BPD) or death. Secondary outcomes included moderate to severe BPD, death, necrotizing enterocolitis (NEC), late-onset sepsis (LOS), days of mechanical ventilation, oxygen supplementation, Z-scores for growth, home oxygen, BPD severity, neurodevelopmental impairment (NDI) ,and moderate to severe cerebral palsy (CP). Analyses for interaction between PDA (defined as treatment to achieve PDA closure) and HC were performed for the primary and secondary outcomes.Of 800 infants enrolled in the NRN HC trial, PDA was treated in 198 HC treated and 197 placebo-treated infants. HC did not modify the relationship of PDA with BPD or death (p=0.93). Regardless of HC treatment, PDA was associated with a significant increase in duration of ventilatory support, oxygen supplementation at 36 weeks postmenstrual age (PMA), BPD severity, decreased weight-for-age Z-score at 36 weeks PMA, moderate to severe BPD ,or death at 36 weeks PMA and home oxygen support.HC after the second postnatal week did not alter the relationship between PDA and BPD or death among infants born extremely preterm. PDA was associated with several adverse outcomes regardless of HC treatment.

View details for DOI 10.1016/j.jpeds.2025.114535

View details for PubMedID 40090543

OBJECTIVE: The primary objective of this study was to determine the relationship between transcutaneous bilirubin (TcB) levels and total serum bilirubin (TSB) levels in extremely preterm infants.STUDY DESIGN: We conducted a prospective multicenter study of extremely preterm infants less than 30 weeks gestation in California. Difference between paired TcB and TSB values were compared based on gestational age, birth weight, maternal race/ethnicity, chronological age as well as during and after phototherapy.RESULTS: TSB values ranged from 0 to 12.6mg/dl and the TcB values ranged from 0 to 14.2mg/dl. TSB was predicted with a high degree of accuracy at TSB=2.37+0.54 (TcB) with r=0.786. There was good correlation across gestational age, birth weight, race/ethnic, chronological age subgroups as well as during and after phototherapy.CONCLUSION: Our study supports the use of TcB as a screening tool for monitoring jaundice in extremely preterm infants.

View details for DOI 10.1038/s41372-022-01477-4

View details for PubMedID 35931798

This study examines comprehensive patient and process factors that influence breast milk use in the NICU setting.We examined the association of maternal, neonatal, and family factors and lactation support systems to identify gaps in breast milk use in a retrospective study of 865 infants born in 23-41 weeks gestation admitted to the NICU.Breast milk at discharge for all infants was 89.3%, for extremely preterm 82.3%, moderately preterm 91.4%, late preterm 86.5%, and term 92.7%. Prematurity (OR 0.31 [0.17-0.56]), low birth weight, morbidities, Black maternal race (OR 0.20 [0.07-0.57]) and public insurance (OR 0.54 [0.34-0.85]) were associated with decreased breast milk use. Early initiation of feeds was associated with increased breast milk use.There is a need to increase social as well as hospital support systems to address gaps in breast milk use in the NICU.

View details for DOI 10.1038/s41372-021-01275-4

View details for PubMedID 34815522

Optimal management of patent ductus arteriosus (PDA) in extremely preterm infants remains controversial. There is paucity of evidence on the benefits of PDA treatment in reducing mortality and morbidities in extremely preterm infants. Failure of randomized clinical trials to demonstrate beneficial effects of PDA treatment on outcomes has often been attributed to open treatment of control subjects. This perspective examines the PDA treatment trials to date, with specific focus on rates of and ages of subjects at open rescue treatment. Although these trials demonstrate that ductal closure is significantly increased with treatment, that does not translate to a significant decrease in major morbidities or mortality in premature infants, even when trials with high rates of rescue treatment of controls are excluded. Trials in which enrollment occurred after 7 days of age include insufficient numbers of subjects to evaluate this relationship.

View details for DOI 10.1038/s41372-020-00848-z

View details for PubMedID 33024260

View details for DOI 10.1016/j.jpeds.2020.09.047

View details for PubMedID 32979387

OBJECTIVE: To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).STUDY DESIGN: We studied children born at 22-26weeks of gestation and assessed at 22-26months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior.RESULTS: Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P<.001) and pervasive developmental problems (P<.001) increased with worsening BPD grade. Sleep problems (P=.008) and aggressive behavior (P=.023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values<.05).CONCLUSIONS: BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

View details for DOI 10.1016/j.jpeds.2019.12.028

View details for PubMedID 32008764

The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants <280/7 weeks of gestation; however 137 potentially eligible infants were not recruited and received treatment of their PDA outside the PDA-TOLERATE trial due to "lack-of-physician-equipoise" (LPE). Despite being less mature and needing more respiratory support, infants with LPE had lower rates of mortality than enrolled infants. Infants with LPE treated before day 6 had lower rates of late respiratory morbidity than infants with LPE treated ≥day 6. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.

View details for DOI 10.1016/j.jpeds.2019.05.049

View details for PubMedID 31255386

To evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks.We performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants).Indomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen = 2.03 (1.05-3.91), and acetaminophen = 1.33 (0.55-3.24). The initial rate of acetaminophen-induced constriction was 27%. Infants with persistent moderate-to-large PDA after acetaminophen were treated with indomethacin. The final rate of constriction after acetaminophen ± indomethacin was 60% (similar to the rate in infants receiving indomethacin-alone (62%)).Indomethacin was more effective than acetaminophen in producing ductus constriction.

View details for DOI 10.1038/s41372-019-0347-4

View details for Web of Science ID 000465460900001

View details for PubMedID 30850756

View details for PubMedCentralID PMC6561645

Management of patent ductus arteriosus in extremely preterm infants remains a topic of debate. Treatment to produce ductal closure was widely practiced until the past decade, despite lack of evidence that it decreases morbidities or mortality. Meta-analyses of trials using nonsteroidal anti-inflammatory drugs have shown effectiveness in accelerating ductal closure, but no reduction in neonatal morbidities, regardless of agent used, indication, timing, gestational age, or route of administration. Surgical ligation closes the ductus but is associated with adverse effects. Recent experience with conservative approaches to treatment suggest improved neonatal outcomes and a high rate of spontaneous ductal closure after discharge. Careful postdischarge follow-up is important, however, because potential adverse effects of long-standing aortopulmonary shunts may be an indication for catheter-based ductal closure. Identification of extremely preterm infants at greatest risk of potential harm from a persistently patent ductus, who may benefit most from treatment are urgently needed.

View details for PubMedID 30811796

To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given.A total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial.At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%).In preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation.ClinicalTrials.gov: NCT01958320.

View details for DOI 10.1016/j.jpeds.2018.09.012

View details for PubMedID 30340932