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Very low birth weight infants after discharge: What do parents describe?
Early Human Development 89 (2013) 343–347
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Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
Very low birth weight infants after discharge: What do parents describe? Juliane Spiegler a,⁎, Martin Schlaud b, Inke R. König c, Norbert Teig d, Mechthild Hubert e, Egbert Herting a, Wolfgang Göpel a and the German Neonatal Network, GNN a
Department of Pediatrics, University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany Robert-Koch-Institute, Nordufer 20, D-13353 Berlin, Germany Institute of Medical Biometry and Statistics, University of Luebeck, Maria-Goeppert-Str. 1, D-23562 Luebeck, Germany d Department of Pediatrics, St. Elisabeth-Hospital, Bleichstrasse 15, D-44791 Bochum, Germany e DRK-Children's Hospital Siegen, Wellersbergstrasse 60, D-57072 Siegen, Germany b c
a r t i c l e
i n f o
Article history: Received 26 September 2012 Received in revised form 24 November 2012 Accepted 27 November 2012 Keywords: Very low birth weight infants Health problems Sleep Development Gender Utilization of health system Hearing
a b s t r a c t Background: Morbidity and mortality in Very Low Birth Weight (VLBW) infants during their hospital stay have been well described. However, there are insufficient data regarding health problems after discharge. Study design: In a multicenter study performed between January 2009 and December 2010 including 2493 VLBW infants, questionnaires were sent out to all participating parents in the first year of life. We compared the parental reported health of VLBW infants with a national cohort (KIGGS). Results: The reported health of VLBW infants born after 29 weeks of gestation was identical to term infants. Even in the group of infants born before 24 weeks of gestation health was regarded as very good or good in > 70% of cases. However, parents described a delayed development in > 50% increasing to > 70% with lower gestational age. In the first year of life VLBW infants have an increased risk of visual and hearing problems. Bronchitis was more frequent in VLBW infants but there were no differences in other infections typical for that age group. VLBW infants had less sleeping problems. No gender differences were described. Conclusion: VLBW infants in our study require slightly more medical care compared to their peers. However, medical problems are relatively small compared to the developmental needs as perceived by their parents. Therefore, close follow-up and advice by specialists in infant development are needed. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Morbidity of very low birth weight infants (VLBW) is well described until discharge. However, problems after discharge during the first year of life have not been characterized in a larger cohort. Ten years ago Jackson et al. [1] described the utilization of the health care system by VLBW infants (N = 36) in Sweden. They demonstrated a nearly 3-fold increase in contacts with healthcare providers. Twenty years ago van Zeben-van der Aa et al. [2] showed that 31% of VLBW infants (N = 998) received physical therapy and 67% attended medical professionals other than their pediatrician. Use of health care services depended on the developmental outcome of the child. Traditionally, former VLBW infants are supposed to suffer more severe respiratory infections. Harding and Howie [3] compared infants in Auckland to Newborn intensive care unit (NICU) survivors. While 8.6% of infants who were never admitted to a NICU had to be ⁎ Corresponding author. Tel.: +49 451 500 2567; fax: +49 451 500 3783. E-mail address: [email protected] (J. Spiegler). 0378-3782/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.earlhumdev.2012.11.007
admitted to a hospital during their first year of life, this rate doubled in former VLBW infants (15.5%). Admissions were largely for respiratory infections. Since the introduction of Palivizumab as a prophylaxis for respiratory syncytial virus infection in at risk VLBW infants, rates of hospitalization after discharge have decreased. However, recently Miller et al. [4] showed that human rhinovirus is the predominant pathogen of the respiratory infections in premature infants in Argentina. Hagen et al. [5] demonstrated that former VLBW infants attending day care had an increased risk of respiratory problems and that bronchopulmonary dysplasia (BPD) and day care attendance increased the risk of respiratory infections but did not act synergistically. The increase in risk was similar to that of term children with one parent with a history of allergy/asthma. Between 2003 and 2006 a large health survey was conducted in Germany. The KIGGS-study (Deutscher Kinder-und Jugendgesundheitssurvey) described a nationwide representative cohort of infants [6]. The aim of our analysis was to compare the parental report of the KIGGS cohort and VLBW infants with regard to medical care (acute and chronic health problems, therapies and prescriptions) and development in the first year of life.
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J. Spiegler et al. / Early Human Development 89 (2013) 343–347
2. Material and methods
2.4. Ethics
2.1. Participants
The study was approved by the local committee on research in human subjects of the University of Luebeck, and the local committees of all participating centers. Written informed parental consent was given for the research and publication of the results of each infant that was included in the study.
Data from VLBW infants born between 22 + 0 and 36 + 6 weeks of gestation and a birth weight of less than 1500 g were collected from 28 centers in Germany. Between 2009 and 2010 a total of 2493 VLBW infants were included in our study. The proper assessment of clinical data was ensured by on-site-monitoring. All parents received the KIGGS survey (1–2 years) in the first year of life. For the comparison group we selected infants of 6 to 12 months of age (n = 935) from a representative cross-sectional German health survey (KIGGS) conducted between 2003 and 2006. 2.2. Definitions Bronchopulmonary dysplasia (BPD) was defined as the need for supplemental oxygen at 36 weeks postmenstrual age, including moderate and severe BPD according to the NIH definition. Intraventricular hemorrhage (IVH) was per definition any bleeding into the cerebral germinal matrix or the ventricles. Surgery for retinopathy of prematurity (ROP) was defined as any ROP treated with laser- or cryocoagulation. Surgery for NEC/FIP was defined as any surgery necessary for intestinal perforation or necrotizing enterocolitis; surgery for PDA was any surgical ligation for persistent ductus arteriosus. The group of children with no adverse events did not suffer from any of the typical complications of prematurity (i.e. no surgery for NEC/FIP/PDA/ROP, no IVH grade 3 or 4). 2.3. Statistical analyses The results from continuous and categorical variables are reported using quartiles and absolute and relative frequencies, respectively. To compare VLBW infants with children from KIGGS, groups were compared using the exact test by Fisher for categorical and Mann– Whitney U-test for continuous variables, respectively. To account for multiple testing, p values were adjusted using the procedure by Simes [7]. For further comparisons, descriptive two-sided p values are reported.
3. Results Of the participating 2493 infants 2408 (97%) were discharged from hospital and 2383 were contacted by questionnaire. 1577 parents answered the questionnaire. The group of children with completed questionnaires is comparable regarding the incidence of surgery for PDA, IVH grade 3 or 4, PVL, to the whole group of VLBW infants included in the study. We noted an increased incidence in surgery for ROP (32/815 (3.9%) vs. 33/1556 (2.1%)) or NEC/FIP (52/822 (6.3%) vs. 48/1568 (3.1%)), BPD (154/825 (18.7%) vs. 230/1575 (14.6%)), a lower gestational age (median Q1/Q3: 28.4 (26.6/30.4) vs. 29.0 (26.9/30.9)) and birth weight (median in g Q1/Q3: 1065 (800/1300) vs. 1110 (850/1350)) in the group that did not answer the questionnaire. There were no differences regarding maternal or paternal education or monthly family income. Mothers who were not native Germans were less likely to answer the questionnaire (279/649 (43%) vs. 1298/1734 (71%)). Comparing those infants with completed questionnaires and the KIGGS cohort, there were no differences regarding nationality (mothers nationality as German: VLBW 1374/1528 (90%) vs. KIGGS 834/930 (90%)) or German as the main language spoken at home (VLBW 1488/1544 (96%) vs. KIGGS 891/930 (96%)). Differences between the VLBW infants and KIGGS cohort are summarized in Table 1. As expected, the VLBW infants required more resources from the health system than the controls. They are seen more often by their primary care physician (mostly a pediatrician in Germany) and ophthalmologist. All the VLBW infants have been to a pediatrician, while 2.2% of the KIGGS cohort has been seen exclusively by family doctors. VLBW infants are more at risk of developing bronchitis, but not a common cold. The frequency of consultations was
Table 1 Health problems/utilization of health system of VLBW infants compared to a national cohort.
Gestational age in weeks Birth weight in g Male sex Age at questionnaire in months Age at questionnaire in months, corrected for prematurity Consultation of physician during last month No. of visits to pediatrician last 12 months Ophthalmologist Common cold Bronchitis Taking prescript medication Hearing problems Hearing aids Lenses Sleep disturbances More medical/social care compared to peers Treatment for developmental/behavioral problems Physical therapy Speech therapy Other/occupational therapy
VLBW
KIGGS-group
N = 1577
N = 935
29 (27–31) 1110 (850–1350) 798 (51.3) 8.9 (8.1–9.9) 6.4 (5.4–7.5) 1240/1532 (80.9%) 6 [4–10] 985/1544 (63.8%) 999/1429 (69.9%) 308/1228 (25.1%) 371/1551 (23.9%) 18/1577 (1.1%) 8/1577 (0.5%) 23/1577 (1.5%) 222/1475 (15.1%) 363/1537 (23.6%) 157/1485 (10.6%) 1167/1577 (74.0%) 45/1577 (2.9%) 225/1577 (14.3%)
39 (38–40) 3400 (3032–3740) 480 (51.3) 7.5 (5.2–9.7) 7.5 (5.2–9.7) 623/921 (67.6%) 5 [4–7] 73/927 (7.9%) 610/892 (68.4%) 132/889 (14.8%) 173/896 (19.3%) 3/935 (0.3%) 0/935 (0.0%) 4/935 (0.4%) 196/882 (22.1%) 27/895 (3.0%) 7/866 (0.8%) 106/935 (11.3%) 3/935 (0.3%) 22/935 (2.4%)
p
Adj p
1.0000
1.0000
1.93E−13 7.84E−23 1.24E−184 0.4592 7.75E−9 0.0087 0.0387 0.0292 0.0155 1.33E−5 3.93E−49 2.27E−24 1.01E−16 1.08E−6 4.52E−26
4.41E−13 2.51E−22 1.98E−183 0.4900 1.55E−08 0.0127 0.0442 0.0359 0.0207 2.13E−05 3.14E−48 9.08E−24 2.69E−16 1.92E−06 2.41E−25
Continuous variables are given as mean (Q1–Q3), binary variables are given as absolute numbers and percentage. Tests: exact test by Fisher for binary variables and Mann–Whitney U-test for continuous variables, two-sided p values; adjusted p values are p values adjusted for multiple testing using the procedure by Simes [7]. Difference in gestational age and birth weight not tested because different by definition, difference in age not tested because not of major interest.
J. Spiegler et al. / Early Human Development 89 (2013) 343–347
70 60 50 very good 40
good average
30
bad very bad
20 10 0 <24
24+0-26+6 27+0-28+6 29+0-36+6
VLBW
KIGGS
Fig. 1. Health as perceived by parents. Data in percentage, given for the whole group and stratified for weeks of gestation.
90 80 70 60 50 40
faster normal slower
30 20 10 0
Fig. 2. Development as perceived by parents. Data in percentage, given for the whole group and stratified for weeks of gestation.
identical in the study and the KIGGS cohort for acute illness, regulatory problems and check-ups. VLBW infants were seen more often due to chronic illnesses, for asking advice and prescriptions by primary
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care physicians, compared to controls. Parents of VLBW infants see more need for medical care in their children compared to their peers and describe more need for treatment for developmental/ behavioral problems. They are more likely to suffer from hearing or visual impairment; they need more lenses and hearing aids. However, regarding the overall health of their children, parents see no differences compared with children born at 29 weeks of gestation or later, and more than 70% of children born at less than 24 weeks have good or very good health according to their parents (Fig. 1). Parents of VLBW infants report less sleeping problems (15.1% vs. 22.1%). Despite this reassuring report about health, parents are concerned about the development of their children. Even in children born at 29 weeks of gestation or later more than 50% of parents describe that their children develop slower than their peers. Perceived delayed development increases with declining gestational age and reaches up to 70% in children born less than 24 weeks of gestation (Fig. 2). Table 2 shows a descriptive comparison of VLBW boys and girls. Former VLBW boys seem to be more at risk of developing bronchitis, compared with girls. But otherwise parents report no gender differences. VLBW boys and girls in our study are seen by medical professionals with the same problems in the same frequency. In our study, VLBW infants who suffered from at least one major complication, compared to those without major complications, were born more premature (26 weeks vs. 29 weeks of gestation) and had accordingly a lower birth weight (820 g vs. 1145 g). VLBW infants with at least one major complication were seen more often by primary care physicians and specialists, took more prescriptions, had more hearing problems and required lenses more often. However, bronchitis and the common cold were seen in the same frequency in both groups. Parents described that infants with major complications needed more medical care and more treatment for developmental/behavioral problems. They received more physical and speech therapy, but the difference in other therapies like early intervention programs was not as pronounced. In our study parents of VLBW infants with at least one major complication described that more medical support is necessary. However, infants with at least one major complication were seen on average only one time more by their primary care physician during the first year of life compared to VLBW infants with no complications and twice more compared to controls (Table 2).
Table 2 Gender differences in VLBW infants/influence of adverse events.
Gestational age in weeks Birth weight in g Male sex Age at questionnaire in months Age at questionnaire in months, corrected for prematurity Consultation of physician during last month No. of visits to pediatrician last 12 months Ophthalmologist Common cold Bronchitis Taking prescript medication Hearing problems Hearing aids Lenses Sleep disturbances More medical/social care compared to peers Treatment for developmental/behavioral problems Physical therapy Speech therapy Other/occupational therapy
VLBW male
VLBW female
N = 810
N= 767
p value
VLBW (no adverse event)
VLBW (adverse events)
N = 1416
N = 159
29 (27–31) 1110 (870–1350)
29 (27–31) 1105 (816–1350)
0.0036 0.1647
9.0 (8.1–9.9) 6.4 (5.4–7.5)
8.9 (8.1–9.9) 6.4 (5.5–7.6)
0.7267 0.2347
29 1145 722/1416 8.9 6.4
0.4349 0.1984 0.6717 0.0945 0.0069 0.3722 0.8147 0.4960 0.6780 0.1450 0.0627 0.6740 0.2283 0.2288 0.2491
1097/1377 6 887/1392 896/1290 274/1115 311/1391 12/1416 6/1416 15/1416 202/1324 283/1384 115/1336 1031/1416 32/1416 193/1416
645/789 6 511/794 534/743 181/639 199/800 10/810 3/810 13/810 104/760 202/789 83/761 610/810 19/810 124/810
(81.7%) (5–10) (64.4%) (71.9%) (28.3%) (24.9%) (1.2%) (0.4%) (1.6%) (13.7%) (25.6%) (10.9%) (75.3%) (2.3%) (15.3%)
595/743 (80.1%) 6 (4–9) 474/750 (63.2%) 465/686 (67.8%) 127/589 (21.6%) 172/751 (22.9%) 8/767 (1.0%) 5/767 (0.7%) 10/767 (1.3%) 118/715 (16.5%) 161/748 (21.5%) 74/724 (10.2%) 557/767 (72.6%) 26/767 (3.4%) 101/767 (13.2%)
(27–31) (890–1365) (51.0%) (8.1–9.9) (5.5–7.5) (79.7%) (4–9) (63.7%) (69.5%) (24.6%) (22.4%) (0.8%) (0.4%) (1.1%) (15.3%) (20.4%) (8.6%) (72.8%) (2.3%) (13.6%)
Continuous variables are given as mean (Q1–Q3), binary variables are given as absolute numbers and percentage. Tests: exact test by Fisher for binary variables and Mann–Whitney U-test for continuous variables, two-sided descriptive p values.
26 820 87/159 9.2 6.2 141/153 7 98/150 101/137 34/112 59/158 5/159 1/159 8/159 19/149 79/151 41/147 134/159 13/159 31/159
p value
(25–28) (650–1060) (54.7%) (8.2–10.4) (5.2–7.5)
9.5E−24 3.8E−21 0.4030 0.0344 0.0775
(92.2%) (5–10) (65.3%) (73.7%) (30.4%) (37.7%) (3.3%) (0.6%) (5.0%) (12.7%) (52.3%) (27.9%) (84.3%) (8.2%) (19.5%)
7.9E−05 0.1115 0.7213 0.3283 0.2080 7.0E−05 0.0223 0.5259 0.0012 0.4691 7.7E−16 2.7E−10 0.0016 0.0003 0.0546
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J. Spiegler et al. / Early Human Development 89 (2013) 343–347
4. Discussion VLBW infants are a fragile group of patients in our neonatal intensive care units. There is an ongoing discussion about the price parents pay for the survival of these very immature infants. In our study we can show some really reassuring data about the outcome of VLBW infants and identify fields in which we ought to improve in the future. Parents regard medical health in VLBW infants born after 29 weeks of gestation identically as good when compared to controls. However, development was regarded as slower in a high percentage even in VLBW infants with no complications and good health. Even though VLBW infants are seen more often by their primary care physician, the difference is smaller than expected. On average VLBW infants have one appointment more than other children during their first months of life. During their first year of life all infants in Germany are seen quite often due to vaccinations and check-ups. Therefore, it would be interesting whether the same would be true during their second year of life since the regular visits of healthy children get very few. The KIGGS questionnaire is very comprehensive regarding the possible infections typical for that age group. In general VLBW infants are not at risk of more infections compared to their peers; however, they suffer more from non-obstructive bronchitis and boys are more at risk than girls in our comparison. Ophthalmologic evaluations are standard care for all VLBW infants due to the risk of ROP. However, even those VLBW infants without a ROP have an increased risk of requiring lenses during their first year of life. There might be an observational bias in these data, since visual impairment in the control group might go unnoticed for a longer period of time, while VLBW infants are closely monitored and visual problems will be detected earlier. Davis et al. [8] studied the auditory function of former VLBW infants at 14 years of age. They found no differences regarding hearing impairment compared to controls, but more children with central auditory processing problems. Nevertheless prematurity has been associated with hearing loss for some time. In most affected VLBW infants there is a transient hearing loss due to middle ear effusions, however, the risk of permanent hearing loss shows a 10-fold increase compared to controls [9]. Known risk factors are ototoxic drugs (i.e. gentamycin, diuretics), noise, hypoxia and hyperbilirubinemia. Reasons for the delayed onset of hearing problems in VLBW infants are not well understood. In our cohort these data are confirmed; hearing problems are more common in VLBW infants and some of them require hearing aids. The VLBW infants in our cohort who required hearing aids have had a hearing screening before discharge (except for the missing data of hearing screening result in one patient). 128 of 1433 did not pass the hearing screening. 5 of these children required hearing aids. However, two VLBW infants passed the screening but required hearing aids just a few months later. 18 parents reported that their children suffer from a permanent hearing loss; of these children 15 had a hearing screening before discharge. Seven infants passed the screening and seemed to have developed permanent hearing problems later. Our data underlines the necessity for hearing screening before the discharge of every VLBW infant as well as regular controls that cover not only conductive hearing loss but sensorineural loss as well. Despite the very good outcome of general health in all groups of VLBW infants, parents are concerned about development. While only 4% of parents of the KIGGS cohort report that their children show a slower development than their peers, more than 50% of parents of “uncomplicated” VLBW infants describe this. While 74% of VLBW infants obtain physical therapy at some point during their first year of life, only 14% receive other therapies (for example early intervention programs). The benefit of early intervention programs is the focus of ongoing research. A number of studies in small groups of VLBW infants showed the benefits of early intervention programs and the Cochrane
analysis showed a positive effect on cognitive outcomes [10]. In our study only 14% of this high risk population receives additional therapy despite the high rate of developmental problems perceived by parents. In VLBW infants with at least one major complication the rate of other therapies increases, but only to 19.5%. However, we have no data whether this perceived developmental delay would be regarded as delay by professionals. Moll et al. [11] published follow-up Bayley Scores at 2 years of age. In their cohort of 372 VLBW infants, 75% showed normal mental developmental indices. Therefore “measured” development may be better than the development “perceived” by parents. Further studies are needed to correlate this early parental opinion with later developmental scores at two years of age or even cognitive/motor/social outcome at school age. Our data emphasize the need for developmental follow-up programs designed to meet parental needs and help to implement additional therapies where indicated by an expert in developmental medicine and child neurology. Sleep–wake patterns are related to brain maturation. Infants born prematurely are supposed to have more regulatory problems including sleep problems. At twelve months of age Asaka and Takada [12] studied 14 VLBW infants and described that they had less restful sleep during nighttimes. They confirmed the data of Gössel-Symank et al. [13] (17 preterm infants at 20 months of age). Sleep disturbances are seen quite often in normal children. 22% of parents reported sleep problems in the KIGGS cohort. There are no data on sleep problems in larger cohorts of VLBW infants. Surprisingly, VLBW infants in our cohort showed significantly less sleep problems (15%). However, sleep patterns are strongly influenced by environment [14]. One could speculate that the strict schedule of NICUs (feeding by the clock), that is often continued by parents after discharge, may prevent sleep problems in VLBW infants despite their immature brain and perhaps other regulatory problems. As parents of VLBW infants have often been confronted with serious medical problems during hospital stay, perhaps their perception of sleep problems is different to parents of the KIGGS cohort during the first year of life. However, even when analyzing times of waking up during the night as a marker for sleep problems, VLBW infants in our cohort seem to sleep better. Even though gender differences in VLBW infants have been described before [15], parents reported no differences in our cohort, except for a higher rate of bronchitis in boys. After discharge boys and girls seem to have the same problems and need the same medical care, according to their parents. These results need further evaluation and comparison with objective parameters like later scores in developmental tests. There are several limitations to our analysis. Parents who were not native speaking Germans were less likely to send back the survey. Therefore this group, that might have a different approach to the health system, is not well covered in our study. However, parental origin in our cohort with completed questionnaires is comparable to the KIGGS cohort. VLBW infants of parents that did not answer the questionnaire suffered slightly more neonatal complications compared to those with completed questionnaires. However, the overall numbers of infants with neonatal complications are relatively small so we think that the group with completed questionnaires represents the health and developmental problems of VLBW infants well. Even though we have objective parameters of all VLBW infants until discharge, the data shown in this paper are uncontrollable parental reports. There are no objective criteria as to how and why parents regard the health or development of their children, normal versus abnormal. The number of visits to doctors or number and character of illnesses are shown as remembered by parents. However, there is no reason why parents of VLBW infants should have different judgments compared to other parents with infants at a similar age. Conflict of interest The authors declare that there are no conflicts of interest.
J. Spiegler et al. / Early Human Development 89 (2013) 343–347
Acknowledgment This study is part of a larger project (German neonatal network, GNN) and is funded by the German Ministry for Education and Research (BMBF-grant-no: 01ER0805). References [1] Jackson K, Schollin J, Bodin L, Ternestedt B-M. Utilization of healthcare by very-low-birthweight infants during their first year of life. Acta Paediatr 2001;90: 213–7. [2] Van Zeben-van der Aa DM, Verwey RA, Verloove-Vanhorick SP, Brand R, Ruys JH. The use of health services in the first 2 years of life in a nationwide cohort of very preterm and/or very low birthweight infants in The Netherlands: rehospitalisation and out-patient care. Paediatr Perinat Epidemiol 1991;5:11–26. [3] Harding JE, Howie RN. First year mortality and hospital morbidity after newborn intensive care. N Z Med J Sep 9 1987;100(831):548–52. [4] Miller EK, Bugna J, Libster R, Shepherd BE, Scalzo PM, Acosta PL, et al. Human rhinoviruses in severe respiratory disease in very low birth weight infants. Pediatrics Jan 2012;129(1):e60–7 [Epub 2011 Dec 26]. [5] Hagen EW, Sadek-Badawi M, Palta M. Day care attendance and risk for respiratory morbidity among young very low birth weight children. Pediatr Pulmonol 2009;44:1093–9. [6] Kurth BM, Kamtsiuris P, Hölling H, Schlaud M, Dölle R, Ellert U, et al. The challange of comprehensively mapping children's health in a nation-wide health survey: design of the German KiGGS-study. BMC Public Health 2008;8:196.
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[7] Simes RJ. An improved Bonferroni procedure for multiple tests of significance. Biometrika 1986;73:751–4. [8] Davis NM, Doyle LW, Keir GW, Michael J, Rickards AL, Kelly EA, et al. Auditory function at 14 years of age of very-low-birthweight. Dev Med Child Neurol 2001;43:191–6. [9] Cristobal R, Oghalai JS. Hearing loss in children with very low birth weight: current review of epidemiology and pathophysiology. Arch Dis Child Fetal Neonatal Ed 2008;93:F462–8. [10] Spittle AJ, Orton J, Doyle LW, Boyed R. Early developmental intervention programs post discharge to prevent motor and cognitive impairments in preterm infants. Cochrane Database Syst Rev 2007;18:CD005495. [11] Moll M, Schöning M, Gölz R, Döbler-Neumann M, Arand J, Krägeloh-Mann I, et al. 2-year follow-up examinations (Bayley II) in infants born at b32 weeks in a German perinatal center. Klin Padiatr 2011;223:251–4. [12] Asaka Y, Takada S. Activity-based assessment of the sleep behavior of VLBW preterm infants and full-term infants at around 12 months of age. Brain Dev 2010;32:150–5. [13] Gössel-Symank R, Grimmer I, Korte J, Siegmund R. Actigraphic monitoring of the activity–rest behavior of preterm and full-term infants at 20 months of age. Chronobiol Int 2004;21:661–71. [14] Anders TF, Keener MA, Kraemer H. Sleep–Wake State Organization, neonatal assessment and development in premature infants during the first year of life II. Sleep 1985;8:193–206. [15] Tyson JE, Parikh NA, Langer J, Green C, Higgins RD. Intensive care for extreme prematurity—moving beyond gestational age. N Engl J Med 2008;358:1672–81.
Contents lists available at SciVerse ScienceDirect
Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
Very low birth weight infants after discharge: What do parents describe? Juliane Spiegler a,⁎, Martin Schlaud b, Inke R. König c, Norbert Teig d, Mechthild Hubert e, Egbert Herting a, Wolfgang Göpel a and the German Neonatal Network, GNN a
Department of Pediatrics, University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany Robert-Koch-Institute, Nordufer 20, D-13353 Berlin, Germany Institute of Medical Biometry and Statistics, University of Luebeck, Maria-Goeppert-Str. 1, D-23562 Luebeck, Germany d Department of Pediatrics, St. Elisabeth-Hospital, Bleichstrasse 15, D-44791 Bochum, Germany e DRK-Children's Hospital Siegen, Wellersbergstrasse 60, D-57072 Siegen, Germany b c
a r t i c l e
i n f o
Article history: Received 26 September 2012 Received in revised form 24 November 2012 Accepted 27 November 2012 Keywords: Very low birth weight infants Health problems Sleep Development Gender Utilization of health system Hearing
a b s t r a c t Background: Morbidity and mortality in Very Low Birth Weight (VLBW) infants during their hospital stay have been well described. However, there are insufficient data regarding health problems after discharge. Study design: In a multicenter study performed between January 2009 and December 2010 including 2493 VLBW infants, questionnaires were sent out to all participating parents in the first year of life. We compared the parental reported health of VLBW infants with a national cohort (KIGGS). Results: The reported health of VLBW infants born after 29 weeks of gestation was identical to term infants. Even in the group of infants born before 24 weeks of gestation health was regarded as very good or good in > 70% of cases. However, parents described a delayed development in > 50% increasing to > 70% with lower gestational age. In the first year of life VLBW infants have an increased risk of visual and hearing problems. Bronchitis was more frequent in VLBW infants but there were no differences in other infections typical for that age group. VLBW infants had less sleeping problems. No gender differences were described. Conclusion: VLBW infants in our study require slightly more medical care compared to their peers. However, medical problems are relatively small compared to the developmental needs as perceived by their parents. Therefore, close follow-up and advice by specialists in infant development are needed. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Morbidity of very low birth weight infants (VLBW) is well described until discharge. However, problems after discharge during the first year of life have not been characterized in a larger cohort. Ten years ago Jackson et al. [1] described the utilization of the health care system by VLBW infants (N = 36) in Sweden. They demonstrated a nearly 3-fold increase in contacts with healthcare providers. Twenty years ago van Zeben-van der Aa et al. [2] showed that 31% of VLBW infants (N = 998) received physical therapy and 67% attended medical professionals other than their pediatrician. Use of health care services depended on the developmental outcome of the child. Traditionally, former VLBW infants are supposed to suffer more severe respiratory infections. Harding and Howie [3] compared infants in Auckland to Newborn intensive care unit (NICU) survivors. While 8.6% of infants who were never admitted to a NICU had to be ⁎ Corresponding author. Tel.: +49 451 500 2567; fax: +49 451 500 3783. E-mail address: [email protected] (J. Spiegler). 0378-3782/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.earlhumdev.2012.11.007
admitted to a hospital during their first year of life, this rate doubled in former VLBW infants (15.5%). Admissions were largely for respiratory infections. Since the introduction of Palivizumab as a prophylaxis for respiratory syncytial virus infection in at risk VLBW infants, rates of hospitalization after discharge have decreased. However, recently Miller et al. [4] showed that human rhinovirus is the predominant pathogen of the respiratory infections in premature infants in Argentina. Hagen et al. [5] demonstrated that former VLBW infants attending day care had an increased risk of respiratory problems and that bronchopulmonary dysplasia (BPD) and day care attendance increased the risk of respiratory infections but did not act synergistically. The increase in risk was similar to that of term children with one parent with a history of allergy/asthma. Between 2003 and 2006 a large health survey was conducted in Germany. The KIGGS-study (Deutscher Kinder-und Jugendgesundheitssurvey) described a nationwide representative cohort of infants [6]. The aim of our analysis was to compare the parental report of the KIGGS cohort and VLBW infants with regard to medical care (acute and chronic health problems, therapies and prescriptions) and development in the first year of life.
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2. Material and methods
2.4. Ethics
2.1. Participants
The study was approved by the local committee on research in human subjects of the University of Luebeck, and the local committees of all participating centers. Written informed parental consent was given for the research and publication of the results of each infant that was included in the study.
Data from VLBW infants born between 22 + 0 and 36 + 6 weeks of gestation and a birth weight of less than 1500 g were collected from 28 centers in Germany. Between 2009 and 2010 a total of 2493 VLBW infants were included in our study. The proper assessment of clinical data was ensured by on-site-monitoring. All parents received the KIGGS survey (1–2 years) in the first year of life. For the comparison group we selected infants of 6 to 12 months of age (n = 935) from a representative cross-sectional German health survey (KIGGS) conducted between 2003 and 2006. 2.2. Definitions Bronchopulmonary dysplasia (BPD) was defined as the need for supplemental oxygen at 36 weeks postmenstrual age, including moderate and severe BPD according to the NIH definition. Intraventricular hemorrhage (IVH) was per definition any bleeding into the cerebral germinal matrix or the ventricles. Surgery for retinopathy of prematurity (ROP) was defined as any ROP treated with laser- or cryocoagulation. Surgery for NEC/FIP was defined as any surgery necessary for intestinal perforation or necrotizing enterocolitis; surgery for PDA was any surgical ligation for persistent ductus arteriosus. The group of children with no adverse events did not suffer from any of the typical complications of prematurity (i.e. no surgery for NEC/FIP/PDA/ROP, no IVH grade 3 or 4). 2.3. Statistical analyses The results from continuous and categorical variables are reported using quartiles and absolute and relative frequencies, respectively. To compare VLBW infants with children from KIGGS, groups were compared using the exact test by Fisher for categorical and Mann– Whitney U-test for continuous variables, respectively. To account for multiple testing, p values were adjusted using the procedure by Simes [7]. For further comparisons, descriptive two-sided p values are reported.
3. Results Of the participating 2493 infants 2408 (97%) were discharged from hospital and 2383 were contacted by questionnaire. 1577 parents answered the questionnaire. The group of children with completed questionnaires is comparable regarding the incidence of surgery for PDA, IVH grade 3 or 4, PVL, to the whole group of VLBW infants included in the study. We noted an increased incidence in surgery for ROP (32/815 (3.9%) vs. 33/1556 (2.1%)) or NEC/FIP (52/822 (6.3%) vs. 48/1568 (3.1%)), BPD (154/825 (18.7%) vs. 230/1575 (14.6%)), a lower gestational age (median Q1/Q3: 28.4 (26.6/30.4) vs. 29.0 (26.9/30.9)) and birth weight (median in g Q1/Q3: 1065 (800/1300) vs. 1110 (850/1350)) in the group that did not answer the questionnaire. There were no differences regarding maternal or paternal education or monthly family income. Mothers who were not native Germans were less likely to answer the questionnaire (279/649 (43%) vs. 1298/1734 (71%)). Comparing those infants with completed questionnaires and the KIGGS cohort, there were no differences regarding nationality (mothers nationality as German: VLBW 1374/1528 (90%) vs. KIGGS 834/930 (90%)) or German as the main language spoken at home (VLBW 1488/1544 (96%) vs. KIGGS 891/930 (96%)). Differences between the VLBW infants and KIGGS cohort are summarized in Table 1. As expected, the VLBW infants required more resources from the health system than the controls. They are seen more often by their primary care physician (mostly a pediatrician in Germany) and ophthalmologist. All the VLBW infants have been to a pediatrician, while 2.2% of the KIGGS cohort has been seen exclusively by family doctors. VLBW infants are more at risk of developing bronchitis, but not a common cold. The frequency of consultations was
Table 1 Health problems/utilization of health system of VLBW infants compared to a national cohort.
Gestational age in weeks Birth weight in g Male sex Age at questionnaire in months Age at questionnaire in months, corrected for prematurity Consultation of physician during last month No. of visits to pediatrician last 12 months Ophthalmologist Common cold Bronchitis Taking prescript medication Hearing problems Hearing aids Lenses Sleep disturbances More medical/social care compared to peers Treatment for developmental/behavioral problems Physical therapy Speech therapy Other/occupational therapy
VLBW
KIGGS-group
N = 1577
N = 935
29 (27–31) 1110 (850–1350) 798 (51.3) 8.9 (8.1–9.9) 6.4 (5.4–7.5) 1240/1532 (80.9%) 6 [4–10] 985/1544 (63.8%) 999/1429 (69.9%) 308/1228 (25.1%) 371/1551 (23.9%) 18/1577 (1.1%) 8/1577 (0.5%) 23/1577 (1.5%) 222/1475 (15.1%) 363/1537 (23.6%) 157/1485 (10.6%) 1167/1577 (74.0%) 45/1577 (2.9%) 225/1577 (14.3%)
39 (38–40) 3400 (3032–3740) 480 (51.3) 7.5 (5.2–9.7) 7.5 (5.2–9.7) 623/921 (67.6%) 5 [4–7] 73/927 (7.9%) 610/892 (68.4%) 132/889 (14.8%) 173/896 (19.3%) 3/935 (0.3%) 0/935 (0.0%) 4/935 (0.4%) 196/882 (22.1%) 27/895 (3.0%) 7/866 (0.8%) 106/935 (11.3%) 3/935 (0.3%) 22/935 (2.4%)
p
Adj p
1.0000
1.0000
1.93E−13 7.84E−23 1.24E−184 0.4592 7.75E−9 0.0087 0.0387 0.0292 0.0155 1.33E−5 3.93E−49 2.27E−24 1.01E−16 1.08E−6 4.52E−26
4.41E−13 2.51E−22 1.98E−183 0.4900 1.55E−08 0.0127 0.0442 0.0359 0.0207 2.13E−05 3.14E−48 9.08E−24 2.69E−16 1.92E−06 2.41E−25
Continuous variables are given as mean (Q1–Q3), binary variables are given as absolute numbers and percentage. Tests: exact test by Fisher for binary variables and Mann–Whitney U-test for continuous variables, two-sided p values; adjusted p values are p values adjusted for multiple testing using the procedure by Simes [7]. Difference in gestational age and birth weight not tested because different by definition, difference in age not tested because not of major interest.
J. Spiegler et al. / Early Human Development 89 (2013) 343–347
70 60 50 very good 40
good average
30
bad very bad
20 10 0 <24
24+0-26+6 27+0-28+6 29+0-36+6
VLBW
KIGGS
Fig. 1. Health as perceived by parents. Data in percentage, given for the whole group and stratified for weeks of gestation.
90 80 70 60 50 40
faster normal slower
30 20 10 0
Fig. 2. Development as perceived by parents. Data in percentage, given for the whole group and stratified for weeks of gestation.
identical in the study and the KIGGS cohort for acute illness, regulatory problems and check-ups. VLBW infants were seen more often due to chronic illnesses, for asking advice and prescriptions by primary
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care physicians, compared to controls. Parents of VLBW infants see more need for medical care in their children compared to their peers and describe more need for treatment for developmental/ behavioral problems. They are more likely to suffer from hearing or visual impairment; they need more lenses and hearing aids. However, regarding the overall health of their children, parents see no differences compared with children born at 29 weeks of gestation or later, and more than 70% of children born at less than 24 weeks have good or very good health according to their parents (Fig. 1). Parents of VLBW infants report less sleeping problems (15.1% vs. 22.1%). Despite this reassuring report about health, parents are concerned about the development of their children. Even in children born at 29 weeks of gestation or later more than 50% of parents describe that their children develop slower than their peers. Perceived delayed development increases with declining gestational age and reaches up to 70% in children born less than 24 weeks of gestation (Fig. 2). Table 2 shows a descriptive comparison of VLBW boys and girls. Former VLBW boys seem to be more at risk of developing bronchitis, compared with girls. But otherwise parents report no gender differences. VLBW boys and girls in our study are seen by medical professionals with the same problems in the same frequency. In our study, VLBW infants who suffered from at least one major complication, compared to those without major complications, were born more premature (26 weeks vs. 29 weeks of gestation) and had accordingly a lower birth weight (820 g vs. 1145 g). VLBW infants with at least one major complication were seen more often by primary care physicians and specialists, took more prescriptions, had more hearing problems and required lenses more often. However, bronchitis and the common cold were seen in the same frequency in both groups. Parents described that infants with major complications needed more medical care and more treatment for developmental/behavioral problems. They received more physical and speech therapy, but the difference in other therapies like early intervention programs was not as pronounced. In our study parents of VLBW infants with at least one major complication described that more medical support is necessary. However, infants with at least one major complication were seen on average only one time more by their primary care physician during the first year of life compared to VLBW infants with no complications and twice more compared to controls (Table 2).
Table 2 Gender differences in VLBW infants/influence of adverse events.
Gestational age in weeks Birth weight in g Male sex Age at questionnaire in months Age at questionnaire in months, corrected for prematurity Consultation of physician during last month No. of visits to pediatrician last 12 months Ophthalmologist Common cold Bronchitis Taking prescript medication Hearing problems Hearing aids Lenses Sleep disturbances More medical/social care compared to peers Treatment for developmental/behavioral problems Physical therapy Speech therapy Other/occupational therapy
VLBW male
VLBW female
N = 810
N= 767
p value
VLBW (no adverse event)
VLBW (adverse events)
N = 1416
N = 159
29 (27–31) 1110 (870–1350)
29 (27–31) 1105 (816–1350)
0.0036 0.1647
9.0 (8.1–9.9) 6.4 (5.4–7.5)
8.9 (8.1–9.9) 6.4 (5.5–7.6)
0.7267 0.2347
29 1145 722/1416 8.9 6.4
0.4349 0.1984 0.6717 0.0945 0.0069 0.3722 0.8147 0.4960 0.6780 0.1450 0.0627 0.6740 0.2283 0.2288 0.2491
1097/1377 6 887/1392 896/1290 274/1115 311/1391 12/1416 6/1416 15/1416 202/1324 283/1384 115/1336 1031/1416 32/1416 193/1416
645/789 6 511/794 534/743 181/639 199/800 10/810 3/810 13/810 104/760 202/789 83/761 610/810 19/810 124/810
(81.7%) (5–10) (64.4%) (71.9%) (28.3%) (24.9%) (1.2%) (0.4%) (1.6%) (13.7%) (25.6%) (10.9%) (75.3%) (2.3%) (15.3%)
595/743 (80.1%) 6 (4–9) 474/750 (63.2%) 465/686 (67.8%) 127/589 (21.6%) 172/751 (22.9%) 8/767 (1.0%) 5/767 (0.7%) 10/767 (1.3%) 118/715 (16.5%) 161/748 (21.5%) 74/724 (10.2%) 557/767 (72.6%) 26/767 (3.4%) 101/767 (13.2%)
(27–31) (890–1365) (51.0%) (8.1–9.9) (5.5–7.5) (79.7%) (4–9) (63.7%) (69.5%) (24.6%) (22.4%) (0.8%) (0.4%) (1.1%) (15.3%) (20.4%) (8.6%) (72.8%) (2.3%) (13.6%)
Continuous variables are given as mean (Q1–Q3), binary variables are given as absolute numbers and percentage. Tests: exact test by Fisher for binary variables and Mann–Whitney U-test for continuous variables, two-sided descriptive p values.
26 820 87/159 9.2 6.2 141/153 7 98/150 101/137 34/112 59/158 5/159 1/159 8/159 19/149 79/151 41/147 134/159 13/159 31/159
p value
(25–28) (650–1060) (54.7%) (8.2–10.4) (5.2–7.5)
9.5E−24 3.8E−21 0.4030 0.0344 0.0775
(92.2%) (5–10) (65.3%) (73.7%) (30.4%) (37.7%) (3.3%) (0.6%) (5.0%) (12.7%) (52.3%) (27.9%) (84.3%) (8.2%) (19.5%)
7.9E−05 0.1115 0.7213 0.3283 0.2080 7.0E−05 0.0223 0.5259 0.0012 0.4691 7.7E−16 2.7E−10 0.0016 0.0003 0.0546
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4. Discussion VLBW infants are a fragile group of patients in our neonatal intensive care units. There is an ongoing discussion about the price parents pay for the survival of these very immature infants. In our study we can show some really reassuring data about the outcome of VLBW infants and identify fields in which we ought to improve in the future. Parents regard medical health in VLBW infants born after 29 weeks of gestation identically as good when compared to controls. However, development was regarded as slower in a high percentage even in VLBW infants with no complications and good health. Even though VLBW infants are seen more often by their primary care physician, the difference is smaller than expected. On average VLBW infants have one appointment more than other children during their first months of life. During their first year of life all infants in Germany are seen quite often due to vaccinations and check-ups. Therefore, it would be interesting whether the same would be true during their second year of life since the regular visits of healthy children get very few. The KIGGS questionnaire is very comprehensive regarding the possible infections typical for that age group. In general VLBW infants are not at risk of more infections compared to their peers; however, they suffer more from non-obstructive bronchitis and boys are more at risk than girls in our comparison. Ophthalmologic evaluations are standard care for all VLBW infants due to the risk of ROP. However, even those VLBW infants without a ROP have an increased risk of requiring lenses during their first year of life. There might be an observational bias in these data, since visual impairment in the control group might go unnoticed for a longer period of time, while VLBW infants are closely monitored and visual problems will be detected earlier. Davis et al. [8] studied the auditory function of former VLBW infants at 14 years of age. They found no differences regarding hearing impairment compared to controls, but more children with central auditory processing problems. Nevertheless prematurity has been associated with hearing loss for some time. In most affected VLBW infants there is a transient hearing loss due to middle ear effusions, however, the risk of permanent hearing loss shows a 10-fold increase compared to controls [9]. Known risk factors are ototoxic drugs (i.e. gentamycin, diuretics), noise, hypoxia and hyperbilirubinemia. Reasons for the delayed onset of hearing problems in VLBW infants are not well understood. In our cohort these data are confirmed; hearing problems are more common in VLBW infants and some of them require hearing aids. The VLBW infants in our cohort who required hearing aids have had a hearing screening before discharge (except for the missing data of hearing screening result in one patient). 128 of 1433 did not pass the hearing screening. 5 of these children required hearing aids. However, two VLBW infants passed the screening but required hearing aids just a few months later. 18 parents reported that their children suffer from a permanent hearing loss; of these children 15 had a hearing screening before discharge. Seven infants passed the screening and seemed to have developed permanent hearing problems later. Our data underlines the necessity for hearing screening before the discharge of every VLBW infant as well as regular controls that cover not only conductive hearing loss but sensorineural loss as well. Despite the very good outcome of general health in all groups of VLBW infants, parents are concerned about development. While only 4% of parents of the KIGGS cohort report that their children show a slower development than their peers, more than 50% of parents of “uncomplicated” VLBW infants describe this. While 74% of VLBW infants obtain physical therapy at some point during their first year of life, only 14% receive other therapies (for example early intervention programs). The benefit of early intervention programs is the focus of ongoing research. A number of studies in small groups of VLBW infants showed the benefits of early intervention programs and the Cochrane
analysis showed a positive effect on cognitive outcomes [10]. In our study only 14% of this high risk population receives additional therapy despite the high rate of developmental problems perceived by parents. In VLBW infants with at least one major complication the rate of other therapies increases, but only to 19.5%. However, we have no data whether this perceived developmental delay would be regarded as delay by professionals. Moll et al. [11] published follow-up Bayley Scores at 2 years of age. In their cohort of 372 VLBW infants, 75% showed normal mental developmental indices. Therefore “measured” development may be better than the development “perceived” by parents. Further studies are needed to correlate this early parental opinion with later developmental scores at two years of age or even cognitive/motor/social outcome at school age. Our data emphasize the need for developmental follow-up programs designed to meet parental needs and help to implement additional therapies where indicated by an expert in developmental medicine and child neurology. Sleep–wake patterns are related to brain maturation. Infants born prematurely are supposed to have more regulatory problems including sleep problems. At twelve months of age Asaka and Takada [12] studied 14 VLBW infants and described that they had less restful sleep during nighttimes. They confirmed the data of Gössel-Symank et al. [13] (17 preterm infants at 20 months of age). Sleep disturbances are seen quite often in normal children. 22% of parents reported sleep problems in the KIGGS cohort. There are no data on sleep problems in larger cohorts of VLBW infants. Surprisingly, VLBW infants in our cohort showed significantly less sleep problems (15%). However, sleep patterns are strongly influenced by environment [14]. One could speculate that the strict schedule of NICUs (feeding by the clock), that is often continued by parents after discharge, may prevent sleep problems in VLBW infants despite their immature brain and perhaps other regulatory problems. As parents of VLBW infants have often been confronted with serious medical problems during hospital stay, perhaps their perception of sleep problems is different to parents of the KIGGS cohort during the first year of life. However, even when analyzing times of waking up during the night as a marker for sleep problems, VLBW infants in our cohort seem to sleep better. Even though gender differences in VLBW infants have been described before [15], parents reported no differences in our cohort, except for a higher rate of bronchitis in boys. After discharge boys and girls seem to have the same problems and need the same medical care, according to their parents. These results need further evaluation and comparison with objective parameters like later scores in developmental tests. There are several limitations to our analysis. Parents who were not native speaking Germans were less likely to send back the survey. Therefore this group, that might have a different approach to the health system, is not well covered in our study. However, parental origin in our cohort with completed questionnaires is comparable to the KIGGS cohort. VLBW infants of parents that did not answer the questionnaire suffered slightly more neonatal complications compared to those with completed questionnaires. However, the overall numbers of infants with neonatal complications are relatively small so we think that the group with completed questionnaires represents the health and developmental problems of VLBW infants well. Even though we have objective parameters of all VLBW infants until discharge, the data shown in this paper are uncontrollable parental reports. There are no objective criteria as to how and why parents regard the health or development of their children, normal versus abnormal. The number of visits to doctors or number and character of illnesses are shown as remembered by parents. However, there is no reason why parents of VLBW infants should have different judgments compared to other parents with infants at a similar age. Conflict of interest The authors declare that there are no conflicts of interest.
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