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Invited Commentary
Pediatrics
August 2, 2021

Neonatal Intensive Care for Very Preterm Infants in China

Author Affiliations
  • 1Division of Neonatology, Stead Family Department of Pediatrics, University of Iowa, Iowa City
JAMA Netw Open. 2021;4(8):e2118940. doi:10.1001/jamanetworkopen.2021.18940

China is home to 1 in 5 people in the world. Every year, the number of infants born in China (>16 million) exceeds the entire population of Sweden.1 Of these 16 million infants, more than 200 000 are estimated to be born very preterm (<32 weeks’ gestation).2

Cao et al3 present the results of a major nationwide effort to characterize the care and outcomes of very preterm infants in neonatal intensive care units (NICUs) in China. At 57 tertiary NICUs across China in 2019 where 9552 very preterm or very low-birth-weight (<1500 g) infants were admitted, 87.6% survived and 51.8% survived without major morbidities. Among the 8171 infants who received what the authors termed complete care, 95.4% survived, and 57.2% survived without major morbidities.

To our knowledge, this is the first major report of very preterm infant outcomes from the Chinese Neonatal Network database, which was launched in January 2019. In countries around the world, neonatal networks serve as a valuable resource for clinical research, benchmarking, and quality improvement.4 A few details should be considered when comparing the authors’ findings3 with those of other national neonatal networks.

First, like the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network in the US, the Chinese Neonatal Network comprises a selected group of tertiary NICUs. Unlike in several other national networks, information on intensive care received outside of tertiary centers is not available from the Chinese Neonatal Network. This distinction matters, because the outcome s and practices in this study should not be extrapolated to nontertiary centers and do not reflect outcomes across the entire population.5

Second, infant mortality, often used as a marker of the quality of public health or medical care, should be interpreted with attention to how infants die.6 Cao et al3 thoughtfully present survival statistics for all very preterm infants admitted to the NICU and for infants who received complete care. They report that 14.5% of infants did not receive complete care because intensive care for these infants was withdrawn by their parents against medical advice. Withdrawal against medical advice accounted for 67.9% (803 of 1182) of the deaths in the study and was inversely related to gestational age, affecting 39.5% (49 of 124) of infants less than or equal to 24 weeks’ gestation and 10.1% (255 of 2530) of infants at 31 weeks’ gestation. Although the authors were unable to describe why medical care was withdrawn, a previous analysis suggested that withdrawal of care in Chinese NICUs was associated with very low birth weight, female sex, and low family income.1

Life and death decisions in the NICU are complex, delicate, and frequently difficult for both families and clinicians. Verhagen and Janvier6 recommend categorizing NICU deaths as occurring while the infants are receiving the full provision of intensive care (including, perhaps, cardiopulmonary resuscitation), due to withdrawal of intensive care for physiologic instability with impending and imminent death, or due to withdrawal of intensive care for concerns about factors such as quality of life or pain, even though the infants might have survived otherwise. Cao et al3 report that rates of several in-hospital morbidities were higher among infants with care withdrawn against medical advice than among infants with complete care. They also report that some cases of withdrawal of care in this study may have been associated with concerns about cost or lack of health insurance or social support. Distinguishing between these reasons for death would provide clarity about how to address infant mortality and improve the ability to make comparisons over time.

Third, the study by Cao et al3 does not present information on infants who did not receive NICU care. In neonatal networks around the world, whether intensive care is intended following preterm birth substantially influences outcome statistics.5 In the US and elsewhere, this effect is particularly pronounced for infants born at less than 24 weeks’ gestation.7 In some parts of China, infants born at less than 28 weeks’ gestation may be considered nonviable and so are registered as stillborn.1 Furthermore, there are differences in receipt of intensive care based on infant sex. The ratio of male to female very preterm infants admitted to the NICU in the Cao et al3 study was 130:100 overall and was inversely correlated with gestational age. Studies in China from 2010 showed a male-to-female ratio of 117:100 in the general birth population and 171:100 in hospitalized neonates.1 In contrast, in an NICU population of very preterm or very low-birth-weight infants born between 2012 and 2018 in the US, the male-to-female ratio was 107:100.8 The outcomes presented by Cao et al3 should only be compared with outcomes of infants admitted to the NICU in other national networks, because these infants reflect a population selected for intensive care.

In publishing these data, Cao et al3 and the Chinese Neonatal Network have brought to the world’s attention the substantial advances made by Chinese neonatology in the past 2 decades.1 Their survey of neonatal intensive care in China identifies several potential opportunities for further investigation. We look forward to future work from this impressive collaboration.

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Article Information

Published: August 2, 2021. doi:10.1001/jamanetworkopen.2021.18940

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Rysavy MA et al. JAMA Network Open.

Corresponding Author: Edward F. Bell, MD, Division of Neonatology, Stead Family Department of Pediatrics, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242 (edward-bell@uiowa.edu).

Conflict of Interest Disclosures: None reported.

References
1.
Sun  B, Shao  X, Cao  Y, Xia  S, Yue  H.  Neonatal-perinatal medicine in a transitional period in China.   Arch Dis Child Fetal Neonatal Ed. 2013;98(5):F440-F444. doi:10.1136/archdischild-2012-302524 PubMedGoogle ScholarCrossref
2.
Chen  C, Zhang  JW, Xia  HW,  et al.  Preterm birth in China between 2015 and 2016.   Am J Public Health. 2019;109(11):1597-1604. doi:10.2105/AJPH.2019.305287 PubMedGoogle ScholarCrossref
3.
Cao  Y, Jiang  S, Sun  J,  et al  Assessment of neonatal intensive care unit practices, morbidity, and mortality among very preterm infants in China.   JAMA Netw Open. 2021;4(8):e2118904. doi:10.1001/jamanetworkopen.2021.18904Google Scholar
4.
Shah  PS, Lee  SK, Lui  K,  et al; International Network for Evaluating Outcomes of Neonates (iNeo).  The International Network for Evaluating Outcomes of very low birth weight, very preterm neonates (iNeo): a protocol for collaborative comparisons of international health services for quality improvement in neonatal care.   BMC Pediatr. 2014;14:110. doi:10.1186/1471-2431-14-110 PubMedGoogle ScholarCrossref
5.
Rysavy  MA, Marlow  N, Doyle  LW,  et al.  Reporting outcomes of extremely preterm births.   Pediatrics. 2016;138(3):e20160689. doi:10.1542/peds.2016-0689 PubMedGoogle Scholar
6.
Verhagen  AAE, Janvier  A.  The continuing importance of how neonates die.   JAMA Pediatr. 2013;167(11):987-988. doi:10.1001/jamapediatrics.2013.3065 PubMedGoogle ScholarCrossref
7.
Rysavy  MA, Li  L, Bell  EF,  et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Between-hospital variation in treatment and outcomes in extremely preterm infants.   N Engl J Med. 2015;372(19):1801-1811. doi:10.1056/NEJMoa1410689 PubMedGoogle ScholarCrossref
8.
King  BC, Richardson  T, Patel  RM,  et al.  Cost of clinician-driven tests and treatments in very low birth weight and/or very preterm infants.   J Perinatol. 2021;41(2):295-304. doi:10.1038/s41372-020-00879-6 PubMedGoogle ScholarCrossref
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