Abstract
BACKGROUND:
Evidence supports delayed cord clamping (DCC) in preterm infants. However, practice variation exists, and many preterm infants do not receive DCC despite multiple benefits and lack of harm. We aim to 1) study the rate of DCC in preterm infants, 2) compare the difference between infants who received DCC and those who did not receive DCC and 3) investigate the reasons for not performing DCC.
METHODS:
We conducted this retrospective study to evaluate DCC practice at our institution since its implementation in September 2015. We collected and analyzed the data on DCC of 30–45 sec duration in inborn infants < 35 weeks gestation admitted to the neonatal intensive care unit from June 2016- June 2019. The primary outcome was the rate of delayed cord clamping.
RESULTS:
Of the 447 infants, 275 (62%) received DCC. The rate of DCC was 36%, 54%, and 66% in infants < 27 weeks, 27–29 weeks and > 30 weeks gestation, respectively (p = 0.001). Infants not receiving DCC were smaller, of lower gestational age, and more likely to be delivered via cesarean section than those who received DCC (p < 0.0001). Infants not receiving DCC had a higher rate of receiving PPV or intubation and a 1minute Apgar score of < 5 compared to those receiving DCC. We could not establish the reason for not performing DCC because of inadequate documentation in the medical records.
CONCLUSIONS:
The rate of DCC is low in clinical practice, particularly among extremely preterm infants.
Abbreviations
delayed cord clamping Positive pressure ventilation Continuous positive pressure ventilation Intensive care nursery Quality improvement
Introduction
Research studies and meta-analyses have highlighted the benefits of delayed cord clamping (DCC) in both term and preterm infants [1–7]. Most professional organizations [World Health Organization, American College of Obstetrics and Gynecologists, American Academy of Pediatrics (AAP), and the Neonatal Resuscitation Program (NRP)] now recommend DCC in preterm infants because of the favorable impact of placental transfusion on short-term neonatal outcomes [8–10]. DCC has been shown to decrease the incidence of hypotension, need for blood transfusion, intraventricular hemorrhage, late onset sepsis, necrotizing enterocolitis, and in-hospital mortality in preterm infants [1, 12].
Despite evidence to support DCC in preterm infants, the adoption in clinical practice has been variable, and little data is available on the rate of DCC in clinical practice. A recent report from California Perinatal Quality Care Collaborative (CPQCC) reported that only 29% of infants received DCC with the hospital rate ranging from 0–74% [13]. Another study from Italy reported performing either DCC or cord milking in less than 50% of deliveries by the centers applying some form of placental transfusion strategy (DCC, cord milking or both), and only 10% of the responders reported DCC in infants below 29 weeks gestation [14].
We implemented the practice of DCC for preterm infants in September 2015. The objective of this study was 1) to study the rate of DCC in preterm infants in a high-risk perinatal center, 2) compare the difference between infants who received DCC (Yes-DCC) and those who did not receive DCC (No-DCC) and 3) investigate the reasons for not performing DCC. We hypothesized that despite the policy and known benefits of this evidence-based practice, infants < 30 weeks gestation, infants of multiple gestation, and infants requiring resuscitation would have a low rate of DCC.
Methods
Setting
Our high-risk academic medical center has a 30-bed Level 3B neonatal intensive care nursery (ICN) with 400 admissions per year. Two-third of the infants admitted to the ICN are inborn, and the rest are transferred from community hospitals for evaluation and management of neonatal problems. We routinely admit infants born less than 35 weeks gestation to the ICN for prematurity, which accounts for 120–130 admissions per year. With the increasing evidence showing benefits of DCC in preterm infants, our neonatal and obstetric team developed and implemented a guideline for DCC for infants < 35 weeks gestation in September 2015. We conducted this retrospective study to evaluate adherence to DCC guidelines from June 2016-June 2019 among inborn infants less than 35 week gestation admitted to the ICN. The Committee for Protection of Human Subjects approved this study.
We defined DCC as deferring cord clamping for at least 30 to 45 sec. The DCC guidelines identify placental abruption and fetal hydrops as a contraindication to DCC. In addition, “clinical instability requiring resuscitation” was an exclusion criteria to provide an “opt-out” option, allowing the resuscitation team discretion to clamp the cord before 30 seconds if they deemed that prompt resuscitation was indicated. Our resuscitation team, which attends all high-risk and preterm deliveries, includes a neonatal nurse practitioner (NNP) or a neonatal-perinatal medicine fellow who leads the team, a NRP-certified nurse, and a respiratory therapist. The obstetrician places the infant below the perineum in a vaginal delivery or on the maternal thigh in cesarean deliveries, and provides stimulation and oral suctioning (if required) to the infant while waiting for 30 to 45 seconds to clamp the cord. The neonatal team leader observes the infant during the DCC process in the delivery or operating room. The labor and delivery nurse actively monitors the time since birth and informs the team at 30 and 45 seconds to clamp the cord. Either the obstetrician or the neonatal provider can decide to abort DCC and clamp the cord before 30 seconds based on the visual assessment of the infant’s clinical status and need for further resuscitation, including PPV or intubation.
Data collection
We extracted data from monthly DCC QI reports from June 2016-June 2019. We collected data for gestational age, birth weight, type of delivery (cesarean vs vaginal), maternal delivery indication, Apgar score, resuscitation at birth [routine care (stimulation including drying and suctioning), continuous positive pressure ventilation (CPAP), positive pressure ventilation (PPV), intubation or chest compression/epinephrine] and reason for not performing DCC (as charted in the medical record). The primary outcome was the rate of DCC. We compared the differences between infants who received DCC (Yes-DCC) and those who did not receive DCC (No-DCC). We also performed a subgroup analysis of DCC based on gestational age (infants < 30 weeks and > 30 but less than 35 weeks).
Statistical analysis
We used mean (±SD), median (interquartile range, IQR), range, and frequency for demographic variables to describe the cohort. We used Student’s t-test (or Mann-Whitney U test for skewed data) for continuous variables, and Fisher’s exact or Pearson’s chi-square test for binomial variables to compare infants who did or did not receive DCC. For all analyses, an a priori p-value was set at p < 0.05. We used STATA12 for data analysis.
Results
We analyzed the data for 447 inborn infants < 35 weeks with the mean±SD birth weight and gestational age of 1708 + 649 grams and 31.6 + 3 weeks, respectively. Two-thirds of the infants were delivered via cesarean section, and 88% of those were under regional anesthesia. While 27% of preterm infants needed only routine newborn care, 27% received CPAP only, 46% received PPV, and 14% required intubation in the delivery room. Only one infant received chest compression and/or epinephrine (Table 1).
Demographics and delivery room resuscitation in infants who did (Yes-DCC) and did not (No-DCC) receive DCC
Demographics and delivery room resuscitation in infants who did (Yes-DCC) and did not (No-DCC) receive DCC
The overall rate of DCC was 62% in this study cohort. Excluding infants with contraindication for DCC (placental abruption and fetal hydrops only), the rate of DCC was 64.8% (267 of 412 infants). The proportion of preterm infants receiving DCC was significantly lower in infants born < 27 weeks and 27–29 weeks gestation (36% and 54% respectively) compared to infants > 30 week gestation (66%) (p = 0.001).
Infants who did not receive DCC were smaller, of lower gestational age, and more likely to be delivered via cesarean section compared to those who received DCC, the difference being statistically significant. Infants who did not receive DCC also had higher rates of receiving PPV (58% vs. 39%, p = 0.01) and endotracheal intubation (24% vs. 8%, p = 0.0001) compared to those in DCC group. A significantly higher proportion of infants who did not receive DCC had 1 minute Apgar score < 5 compared to those who received DCC (58% vs. 42%, p = 0.0001) (Table 1).
We did not observe any difference in birth weight, gestational age, sex, type of gestation (single vs. multiple), and mode of delivery between those receiving DCC and those not receiving DCC within the subgroup of infants born < 30 weeks and those born > 30 weeks (Table 2). The rate of PPV and endotracheal intubation remained significantly higher among infants who did not receive DCC in both gestational age subgroups. Interestingly, the proportion of infants with one minute Apgar score < 5 was significantly higher in those who did not receive DCC in the subset of infants > 30 week gestation, but not in the subgroup < 30 week gestation (Table 2).
Demographics and delivery room resuscitation in infants who did (Yes-DCC) and did not (No-DCC) receive DCC by gestational age subgroup
Only 10% of infants had the reason for not performing DCC documented in the medical records, the most common being maternal hemorrhage.
In this single-center retrospective cohort study, 62% of preterm infants born less than 35 week gestation received DCC. Our findings were consistent with the hypothesis that infants > 30 weeks gestation, born vaginally, or not receiving resuscitation (PPV or intubation) were more likely to receive DCC than infants born at < 30 weeks gestation, delivered via cesarean section or infants who received resuscitation. Our study also highlights the low rate of DCC in very preterm infants who are most likely to benefit from delayed cord clamping [13, 14].
The adoption of DCC practice varies widely across hospitals and uptake has been especially low for preterm births. California Perinatal Quality Care Collaborative reported 29% rate of DCC among 52 California NICUs in 2016. The rate of DCC was 37% in all preterm infants born < 32 weeks and only 20% among infants < 28 weeks gestation, with hospital rates ranging from 0–74% [13]. An Italian national survey reported 75% of the centers applying placental transfusion strategy (DCC or cord milking or both) but in less than 50% of the deliveries. Only 10% of the responders reported performing DCC in infants less than 29 weeks gestation in that report [14]. Single-center studies describing DCC as quality improvement initiatives have claimed much higher rates, ranging from 53–94% but they differ in their eligibility criteria (such as gestational age ranging from < 28 weeks to < 37 weeks), exclusion criteria’s and duration of DCC (30–60 sec) [15–18].
Our study emphasizes the association of infants not receiving DCC due to the clinical team’s perceived ‘need for resuscitation’ in non-vigorous preterm infants. Based on the high proportion of infants receiving PPV or intubation and one minute Apgar score < 5 in those not receiving DCC, we speculate that the need for resuscitation was likely the reason for not performing DCC in most preterm infants. However, we could not firmly establish the reason(s) for not performing DCC in our cohort because of the lack of documentation in the medical records. The Italian survey described logistic and pragmatic difficulties and lack of knowledge about the procedure as the most common reason (37% and 23% of the responders, respectively) for not applying strategies for placental transfusion. Only 14% of respondents in that study reported concern for infant safety as the reason for not performing DCC [14]. A large RCT comparing delayed cord clamping vs. immediate cord clamping in preterm infants reported that 27% of infants randomized to receive DCC did not receive the intended intervention. The clinical concerns for infant well-being and the need to initiate resuscitation urgently accounted for 70% of those incidences [11].
There is lack of clear guidance and limited evidence on cord clamping in non-vigorous or non-breathing infants in need of resuscitation. DCC trials excluded the newborns requiring resuscitation and a significant proportion of infants included in those trials were clamped earlier than scheduled because of concerns of delaying resuscitation. At present, ILCOR (2010 International Committee on Resuscitation) states that ‘evidence is insufficient to recommend a time for cord clamping for those who require resuscitation ’ [10]. The Clinician’s dilemma is whether waiting for at least 30 sec to perform DCC in a non-vigorous non-breathing infant would delay resuscitation and worsen neonatal outcome. An observational study reported spontaneous breathing in most preterm infants when cord clamping was delayed beyond 60 seconds [19]. And a recent RCT showed no difference in placental transfusion or neonatal outcomes with the use of assisted ventilation with DCC when compared to DCC with stimulation only [20].
We acknowledge certain limitations of our study. The retrospective study design, single-center data and small sample size of very preterm infants in our cohort limit the generalizability of results to centers with different DCC protocols and context. The major limitation of the retrospective study design was our inability to gather data on reasons for not performing DCC due to inadequate documentation in medical records.
In summary, we conclude that a significant proportion of infants, especially extremely preterm infants, do not receive DCC. Improving compliance with DCC guidelines represents an excellent opportunity for audit, feedback, and quality improvement interventions. A focus on improving DCC in non-vigorous preterm infants should consider the knowledge, attitude, and competencies of both obstetric and neonatal care providers. Developing a ‘forced function’ mechanism to standardize and improve documentation of key variables including the infant’s clinical status and level of resuscitation before cord clamping, the actual time of cord clamping, and the reasons for not performing DCC will further inform QI efforts. Future research is required to test alternative approaches to resuscitation of non-vigorous and non-breathing preterm infants in the delivery room to facilitate DCC.