Acta Pædiatrica ISSN 0803-5253
REGULAR ARTICLE
Population-based study shows improved postnatal growth in preterm very-low-birthweight infants between 1995 and 2010 Noa Ofek Shlomai ([email protected])1, Brian Reichman2,3, Liat Lerner-Geva2,3, Valentina Boyko2, Benjamin Bar-Oz1, in Collaboration with the Israel Neonatal Network 1.Department of Neonatology, Hadassah and Hebrew University Medical Center, Jerusalem, Israel 2.Women and Children’s Health Research Unit, Gertner Institute, Tel Hashomer, Israel 3.Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Keywords Extrauterine growth restriction, Extrauterine growth retardation, Postnatal growth failure, Preterm infants, Very low birthweight Correspondence N Ofek Shlomai, Department of Neonatology, Hadasssah and Hebrew University Medical Center, Mt Scopus, Jerusalem 91240, PO box 24035, Israel. Tel: +972725844432 | Fax: +97225813068 | Email: [email protected] Received 6 July 2013; revised 23 October 2013; accepted 20 January 2014. DOI:10.1111/apa.12569
ABSTRACT Aim: To assess whether the postnatal growth of preterm very-low-birthweight (VLBW) infants, as determined by measures of postnatal growth failure (PNGF), improved during the period 1995–2010 and to evaluate postnatal growth by gestational age (GA) and intrauterine growth groups. Methods: The study was based on the Israel national VLBW infant database and comprised 13 531 VLBW infants of 24–32 weeks’ GA, discharged at a postmenstrual age of ≤40 weeks. Z-scores were determined for weight at birth and discharge. Severe and mild PNGF was defined as a decrease >2 and 1–2 z-scores, respectively. Three time periods were considered: 1995–2000, 2001–2005 and 2006–2010. Multinomial logistic regression was used to assess the independent effect of time period on PNGF. Results: Severe PNGF decreased from 11.7% in 1995–2000 to 7.2% in 2001–2005 and 5.2% in 2006–2010. Infants born in 2006–2010 had sixfold lower odds for severe PNGF than babies born in 1995–2000 (adjusted odds ratio 0.17, 95% confidence interval 0.14– 0.21) and 2 in z-scores for weight between birth and discharge. Among infants born at ≤30 weeks’ GA,
Key notes
This study aimed to assess whether the postnatal growth of preterm 13 531 very-low-birthweight (VLBW) infants in Israel improved during the period 1995– 2010, by using data from a national database. Severe postnatal growth failure (PNGF) decreased from 11.7% in 1995–2000 to 7.2% in 2001–2005 and 5.2% in 2006–2010. This significant decline in PNGF was even noted in extremely premature infants and indicates that postnatal growth has improved in Israel.
©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. 498–503
Ofek Shlomai et al.
Improved postnatal growth in VLBW infants
database coordinator is cross-checked against the national birth registry, and data on any missing infant are requested from the birth hospital. Data are collected on all infants until discharge home or death. Birth hospital and patient identification remain confidential by consensus agreement of all the participating centres. This study was approved by the Helsinki committee of the Sheba Medical Centre, Tel Hashomer, Israel. (Number 9641-12-SMC, June 21st 2012).
Embleton et al. (13) reported a mean decline in z-scores of 1.14 between birth and 5 weeks of age. Over the past two decades, improving perinatal and neonatal care has contributed to the improved survival, free of major complications, of preterm and VLBW infants (14). Furthermore, neonatologists have become increasingly aware of the significant implications of early nutrition on short-term and long-term outcomes in VLBW infants (1,15,16). Since 1995, the Israel national VLBW Infant database has prospectively collected data on all VLBW infants. The aim of our population-based study was to determine whether the postnatal growth of preterm VLBW infants, as determined by the rates of PNGF, had improved during the period 1995–2010 and to evaluate postnatal growth over this period by gestational age and intrauterine growth groups.
Study population Over the 16-year period 1995–2010, a total of 24 250 infants with birthweights (BW) of ≤1500 gr were included in the database, accounting for >99% of all VLBW infants born in Israel. For the purpose of this study, we included infants born at 24–32 weeks’ gestation and discharged home at a PMA of 40 weeks or less (Fig. 1). The study population comprised 13 531 infants, after we excluded the following: infants born 32 weeks’ gestation (n = 3171), death before discharge (n = 3407), congenital anomalies (n = 1071), infants with missing discharge weight (n = 164) and infants discharged later than 40 weeks’ PMA (n = 1772). For the purpose of this study, three approximately equal time periods were considered: 1995–2000 (n = 4653 infants), 2001–2005 (n = 4451) and 2006–2010 (n = 4517).
PATIENTS AND METHODS This study is based on an analysis of data collected by the Israel Neonatal Network on VLBW infants (≤1500 g) born in Israel from 1995 to 2010. All 28 neonatal departments in Israel collect data for the Israel National VLBW Infant Database (see Appendix 1). Data collection Data were prospectively collected on a structured form that includes parental demographic details, maternal pregnancy history and antenatal care, delivery details, the infant’s status at birth, diagnoses, procedures and complications during the hospitalisation period and outcome at discharge. In Israel, all live-born infants receive a unique identification number at birth. Patient information received by the
Definitions Definitions used were concordant with those of the Vermont Oxford Neonatal Database manual of operations and have been previously reported in detail (10,17). Gestational age (GA) in completed weeks was defined as the best estimate of GA on the basis of last menstrual period, obstetric history and examination, prenatal ultrasound and
Live Births 1995-2010 N = 24,250
Excluded: • Gestational age 32 wk : n = 3,171 • Death before discharge : n = 3,407 • Congenital malformations : n = 1,071 • Missing discharge weight : n = 164 • Discharged >40 wk post menstrual age (n = 1,772)
Study Population n = 13,531
Severe PNGF decrease >2 z-score n = 1091 (8.1%)
Mild PNGF decrease 1-2 z-score n = 4,800 (35.5%)
No PNGF decrease twofold lower risk for mild PNGF aOR 0.42, (95% CI 0.39–0.48). Severe PNGF was independently associated with lower gestational age (aOR 1.53 for each week) and with a higher z-score at birth (aOR 3.17 for every increase in one unit). PNGF was independently associated with major neonatal morbidities including respiratory distress syndrome, more so in mechanically ventilated infants (aOR 3.86), patent ductus arteriosus (aOR 1.85), late onset sepsis (aOR 2.3), bronchopulmonary dysplasia (aOR 1.38), severe intraventricular haemorrhage (aOR 1.63) and necrotising enterocolitis (aORs of 7.31 for medically and 18.1 for surgically treated necrotising enterocolitis). The odds for mild PNGF followed the same pattern. Table S3 presents a subgroup analysis of PNGF in the different time periods by gestational age and intrauterine growth (SGA and AGA infants) groups. In 1995–2000, infants born at 24–26 weeks of gestation had a 39.6% rate of severe PNGF at discharge, whereas in 2006–2010, this rate had decreased to 18.6%. This decrease was also present in the higher GA groups: 16.2% vs. 6.3% at 27–29 weeks, and 2.8% vs. 0.7% at 30–32 weeks, and in both appropriate for gestational age
Severe PNGF
Mild PNGF
No PNGF
70
Percent PNGF
early postnatal physical examination. Gender-specific birthweight z-scores and percentiles were determined according to the intrauterine growth charts of Kramer et al. (18). Small for gestational age (SGA) was defined as a birthweight below the 10th percentile for GA. PMA at discharge was calculated as gestational age plus chronological age at discharge in weeks. Major neonatal morbidities included the following: respiratory distress syndrome, patent ductus arteriosus, necrotising enterocolitis, late onset sepsis, intraventricular haemorrhage grades 3–4 and bronchopulmonary dysplasia. Definitions of the morbidities have previously been reported in detail (10,19). Bronchopulmonary dysplasia was defined as clinical evidence of Bronchopulmonary dysplasia together with the requirement of oxygen therapy at 36 weeks’ PMA. For each infant, weight at birth and at discharge was converted to a z-score according to the gender-specific Canadian reference charts for BW for GA (18). Means and standard deviation (SD) are tabulated to allow calculation of z-score for BW, where z= (observed BW – expected BW)/ SD. Changes in z-score were calculated by subtracting the z-score at birth from that at discharge. ‘Severe PNGF’ was defined as a decrease of >2 z-scores and ‘mild PNGF’ as a decrease of 1–2 z-scores (9,10). Infants with a decrease of threefold decline in the odds of developing severe PNGF in the 2001–2005 group and a sixfold decrease in the 2006–2010 group compared with the 1995–2000 cohort. As infants’ weight at discharge below the 10th percentile of expected weight has commonly been regarded as postnatal or EUGR (5–8), we also considered this measurement, observing a significant decline from 72.9% in 1995–2000 to 56.8% in 2006–2010. The two definitions of PNGF or EUGR have some limitations and interest. Growth values
REGULAR ARTICLE
Population-based study shows improved postnatal growth in preterm very-low-birthweight infants between 1995 and 2010 Noa Ofek Shlomai ([email protected])1, Brian Reichman2,3, Liat Lerner-Geva2,3, Valentina Boyko2, Benjamin Bar-Oz1, in Collaboration with the Israel Neonatal Network 1.Department of Neonatology, Hadassah and Hebrew University Medical Center, Jerusalem, Israel 2.Women and Children’s Health Research Unit, Gertner Institute, Tel Hashomer, Israel 3.Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Keywords Extrauterine growth restriction, Extrauterine growth retardation, Postnatal growth failure, Preterm infants, Very low birthweight Correspondence N Ofek Shlomai, Department of Neonatology, Hadasssah and Hebrew University Medical Center, Mt Scopus, Jerusalem 91240, PO box 24035, Israel. Tel: +972725844432 | Fax: +97225813068 | Email: [email protected] Received 6 July 2013; revised 23 October 2013; accepted 20 January 2014. DOI:10.1111/apa.12569
ABSTRACT Aim: To assess whether the postnatal growth of preterm very-low-birthweight (VLBW) infants, as determined by measures of postnatal growth failure (PNGF), improved during the period 1995–2010 and to evaluate postnatal growth by gestational age (GA) and intrauterine growth groups. Methods: The study was based on the Israel national VLBW infant database and comprised 13 531 VLBW infants of 24–32 weeks’ GA, discharged at a postmenstrual age of ≤40 weeks. Z-scores were determined for weight at birth and discharge. Severe and mild PNGF was defined as a decrease >2 and 1–2 z-scores, respectively. Three time periods were considered: 1995–2000, 2001–2005 and 2006–2010. Multinomial logistic regression was used to assess the independent effect of time period on PNGF. Results: Severe PNGF decreased from 11.7% in 1995–2000 to 7.2% in 2001–2005 and 5.2% in 2006–2010. Infants born in 2006–2010 had sixfold lower odds for severe PNGF than babies born in 1995–2000 (adjusted odds ratio 0.17, 95% confidence interval 0.14– 0.21) and 2 in z-scores for weight between birth and discharge. Among infants born at ≤30 weeks’ GA,
Key notes
This study aimed to assess whether the postnatal growth of preterm 13 531 very-low-birthweight (VLBW) infants in Israel improved during the period 1995– 2010, by using data from a national database. Severe postnatal growth failure (PNGF) decreased from 11.7% in 1995–2000 to 7.2% in 2001–2005 and 5.2% in 2006–2010. This significant decline in PNGF was even noted in extremely premature infants and indicates that postnatal growth has improved in Israel.
©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. 498–503
Ofek Shlomai et al.
Improved postnatal growth in VLBW infants
database coordinator is cross-checked against the national birth registry, and data on any missing infant are requested from the birth hospital. Data are collected on all infants until discharge home or death. Birth hospital and patient identification remain confidential by consensus agreement of all the participating centres. This study was approved by the Helsinki committee of the Sheba Medical Centre, Tel Hashomer, Israel. (Number 9641-12-SMC, June 21st 2012).
Embleton et al. (13) reported a mean decline in z-scores of 1.14 between birth and 5 weeks of age. Over the past two decades, improving perinatal and neonatal care has contributed to the improved survival, free of major complications, of preterm and VLBW infants (14). Furthermore, neonatologists have become increasingly aware of the significant implications of early nutrition on short-term and long-term outcomes in VLBW infants (1,15,16). Since 1995, the Israel national VLBW Infant database has prospectively collected data on all VLBW infants. The aim of our population-based study was to determine whether the postnatal growth of preterm VLBW infants, as determined by the rates of PNGF, had improved during the period 1995–2010 and to evaluate postnatal growth over this period by gestational age and intrauterine growth groups.
Study population Over the 16-year period 1995–2010, a total of 24 250 infants with birthweights (BW) of ≤1500 gr were included in the database, accounting for >99% of all VLBW infants born in Israel. For the purpose of this study, we included infants born at 24–32 weeks’ gestation and discharged home at a PMA of 40 weeks or less (Fig. 1). The study population comprised 13 531 infants, after we excluded the following: infants born 32 weeks’ gestation (n = 3171), death before discharge (n = 3407), congenital anomalies (n = 1071), infants with missing discharge weight (n = 164) and infants discharged later than 40 weeks’ PMA (n = 1772). For the purpose of this study, three approximately equal time periods were considered: 1995–2000 (n = 4653 infants), 2001–2005 (n = 4451) and 2006–2010 (n = 4517).
PATIENTS AND METHODS This study is based on an analysis of data collected by the Israel Neonatal Network on VLBW infants (≤1500 g) born in Israel from 1995 to 2010. All 28 neonatal departments in Israel collect data for the Israel National VLBW Infant Database (see Appendix 1). Data collection Data were prospectively collected on a structured form that includes parental demographic details, maternal pregnancy history and antenatal care, delivery details, the infant’s status at birth, diagnoses, procedures and complications during the hospitalisation period and outcome at discharge. In Israel, all live-born infants receive a unique identification number at birth. Patient information received by the
Definitions Definitions used were concordant with those of the Vermont Oxford Neonatal Database manual of operations and have been previously reported in detail (10,17). Gestational age (GA) in completed weeks was defined as the best estimate of GA on the basis of last menstrual period, obstetric history and examination, prenatal ultrasound and
Live Births 1995-2010 N = 24,250
Excluded: • Gestational age 32 wk : n = 3,171 • Death before discharge : n = 3,407 • Congenital malformations : n = 1,071 • Missing discharge weight : n = 164 • Discharged >40 wk post menstrual age (n = 1,772)
Study Population n = 13,531
Severe PNGF decrease >2 z-score n = 1091 (8.1%)
Mild PNGF decrease 1-2 z-score n = 4,800 (35.5%)
No PNGF decrease twofold lower risk for mild PNGF aOR 0.42, (95% CI 0.39–0.48). Severe PNGF was independently associated with lower gestational age (aOR 1.53 for each week) and with a higher z-score at birth (aOR 3.17 for every increase in one unit). PNGF was independently associated with major neonatal morbidities including respiratory distress syndrome, more so in mechanically ventilated infants (aOR 3.86), patent ductus arteriosus (aOR 1.85), late onset sepsis (aOR 2.3), bronchopulmonary dysplasia (aOR 1.38), severe intraventricular haemorrhage (aOR 1.63) and necrotising enterocolitis (aORs of 7.31 for medically and 18.1 for surgically treated necrotising enterocolitis). The odds for mild PNGF followed the same pattern. Table S3 presents a subgroup analysis of PNGF in the different time periods by gestational age and intrauterine growth (SGA and AGA infants) groups. In 1995–2000, infants born at 24–26 weeks of gestation had a 39.6% rate of severe PNGF at discharge, whereas in 2006–2010, this rate had decreased to 18.6%. This decrease was also present in the higher GA groups: 16.2% vs. 6.3% at 27–29 weeks, and 2.8% vs. 0.7% at 30–32 weeks, and in both appropriate for gestational age
Severe PNGF
Mild PNGF
No PNGF
70
Percent PNGF
early postnatal physical examination. Gender-specific birthweight z-scores and percentiles were determined according to the intrauterine growth charts of Kramer et al. (18). Small for gestational age (SGA) was defined as a birthweight below the 10th percentile for GA. PMA at discharge was calculated as gestational age plus chronological age at discharge in weeks. Major neonatal morbidities included the following: respiratory distress syndrome, patent ductus arteriosus, necrotising enterocolitis, late onset sepsis, intraventricular haemorrhage grades 3–4 and bronchopulmonary dysplasia. Definitions of the morbidities have previously been reported in detail (10,19). Bronchopulmonary dysplasia was defined as clinical evidence of Bronchopulmonary dysplasia together with the requirement of oxygen therapy at 36 weeks’ PMA. For each infant, weight at birth and at discharge was converted to a z-score according to the gender-specific Canadian reference charts for BW for GA (18). Means and standard deviation (SD) are tabulated to allow calculation of z-score for BW, where z= (observed BW – expected BW)/ SD. Changes in z-score were calculated by subtracting the z-score at birth from that at discharge. ‘Severe PNGF’ was defined as a decrease of >2 z-scores and ‘mild PNGF’ as a decrease of 1–2 z-scores (9,10). Infants with a decrease of threefold decline in the odds of developing severe PNGF in the 2001–2005 group and a sixfold decrease in the 2006–2010 group compared with the 1995–2000 cohort. As infants’ weight at discharge below the 10th percentile of expected weight has commonly been regarded as postnatal or EUGR (5–8), we also considered this measurement, observing a significant decline from 72.9% in 1995–2000 to 56.8% in 2006–2010. The two definitions of PNGF or EUGR have some limitations and interest. Growth values
