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Nascita pretermine nella Regione Veneto: outcome a breve e lungo termine in uno studio di coorte area based
INTRODUCTION
Preterm birth, defined as the birth of a baby of less than 37 weeks gestational age, has a number of consequences at social, ethical, economic and health care level. These consequences affect both hospital health care programs, local programs and prevention plans. The rapid and remarkable innovation of assistance methods and of equipment in the Neonatal Intensive Care Unit has allowed a gradual increase of survival rates of extremely low weight and low gestational age premature infants. Several studies have demonstrated that premature and extremely premature infants show severe short, medium and long-term clinical outcomes, in particular neurological and neurosensorial outcomes. However, long-term follow-ups of infants cohorts selected by area-based surveillance are not available.
AIM
The aim of this study is to analyse the clinical outcomes of preterm infants in the Veneto Region by means of a follow-up assessment of short, medium and long-term health outcomes according to gestational age, in particular for extremely low weight and extremely low gestational age premature infants.
MATERIALS AND METHODS
The study has been divided into different phases. In the first preliminary phase a stratification sampling of population has been carried out on the basis of the gestational age of all infants born in the Veneto Region from 2003 to 2009. For this phase the current flow of the Certificate of Delivery Care (CEDAP) has been used. This flow has been mandatory since 2001 and records all newborns of the Region, it contains information on the infant (gender, weight, length, head circumference, gestational age, major resuscitation care in case of assisted intubation and ventilation and medical cardiac resuscitation, minor resuscitation care in case of aspiration and cardiac massage, infant’s admission in neonatal intensive care unit, possible malformations and possible cause of infant mortality), on the delivery (single or multiple, natural or cesarean, possible type of pain relief and type of anesthetic, maternal complications), on pregnancy (number of tests and ultrasound scans, prenatal diagnosis, course of pregnancy: physiological or pathological, threatened abortion, threatened preterm labour, infectious diseases, infections of the genitourinary tract, diabetes and gestosis) and on the mother and the father (age, education, job, marital status, exposure to risk factors such as smoke).
Stratification sampling has been carried out according to the gestational week (GW) from 20 GW to 42 GW. In particular, all newborns ≤ 28 gestational weeks in the above mentioned period have been considered. Patients cohorts have thus been arranged and the cohorts of infants born in 2005 and from 2007 to 2009 have been studied. In the next phase, starting from current statistics, patients’ natural history has been reconstructed, when possible, by means of death certificates (ISTAT) in order to assess survival, hospital discharge records for recoveries, intercurrent acute pathologies and chronic pathologies, information flow on the rehabilitation activity ex art. 26 L 833/1978 of the Veneto Region in order to assess the admission to rehabilitative services and the flow Rare Diseases Registry.
In particular, the “chronic” patients have been identified, defined as subjects with at least 2 hospitalizations within 12 months, both characterized by the same pathology code of hospital discharge records.
Eventually the results have been analysed: mortality, survival rate, patients affected by chronic pathologies, patients affected by rare diseases and patients who have undergone rehabilitation cycles. The patients not included in the categories described above will be sampled and assessed in follow-up after this study according to the following protocol: qualitative assessment of spontaneous motor function, qualitative assessment by means of classification systems (ABC, Gross Motor Function Measure, and, for the most severe cases, Besta scale and QUEST scale), cognitive assessment (Griffiths, WIPPSI, WISC-IV), neurosensorial assessment by means of the analysis of the Multimodal Evoked Potentials (PEV, BAEPs, SEP), assessment of neuroimaging (standard protocol and 3D brain NMRI with DTI and resting state for tractographic assessment).
RESULTS
During the analysed period from 2003 to 2009 in the Veneto Region 322.598 neonates have been recorded, approximately 46.000 neonates/year. 91,71% of these were born at term (>37 GW), 7,63% were born premature (<37 GW). If we consider preterm neonates, 2,13% were born before 32 GW and 0,55% are ≤ 28 GW. The recorded premature neonates ≤ 28 GW, who are 0,55% of the total amount, are approximately 1785, on average 255/year. Birth mortality total rate in neonates between 2003 and 2009 is 2,9 x 1000 in single deliveries and 8,7 x 1000 in multiple deliveries; the rate grows along with the decrease of gestational age, in particular rates of 8,3 at 36 GW for single deliveries vs 1,1 for multiple deliveries are recorded, 17,8 for single deliveries (35 GW) vs 6,0 for multiple deliveries and 117,6 for single deliveries vs 57,7 for multiple deliveries in neonates born before 28 GW.
Premature babies <28 GW increased from 201 in 2003 (0,48% of neonates in 2003) to 301 in 2009 (0,63% of neonates in 2009).
Multiple deliveries of neonates < 28 GW are 24% (20% twins, 3% multiple twins) in comparison to 1,2 % of babies born at term (2,7% twins and 0,1% multiple twins) and 3% in comparison to the total amount of deliveries.
The percentage of extremely low weight and gestational age neonates and their survival are thus growing rapidly in the Veneto Region. This is due to the growing innovation of care methods and of equipment in the Neonatal Intensive Care Units: even babies born at 20 GW are resuscitated and survive (1 baby born in 2007 recorded, 1 at 19 GW and 1 at 20 GW; in 2008 7 babies born at 21 GW, only two neonatal deaths). Our analysis shows that apparently some factors are implied in preterm birth: one factor is the mother’s age, in particular the percentage of neonates 40 years old (relative risk RR is of 2,3). Another factor is the mother’s ethnic group: among African women and Eastern European women the percentage of preterm neonates is twice as high as among Italian women.
If we analyse the women who have delivered preterm babies, 55% are primiparas (RR 1.2), 30% report a spontaneous abortion in their anamnesis before the delivery (RR 1.8), 4% report a stillbirth before the delivery (RR 3.1) and 12% report a voluntary interruption of pregnancy (RR 2.1). 7% are smokers (RR 1.1) and 2,6% undergo medically assisted procreation or MAP (RR 2.03).
With regard to MAP, 1.8% babies are born every year; 11% of the neonates ≤28 GW were born by means of MAP vs 1% of babies born at term by means of MAP.
If we now analyse the results of neonates born < 28 GW in 2005 and 2007-2009 cohorts, in 2005 the babies who died during the first year of life are 65 (29%); the survivors are 160 (71%).
11 survivors out of the total amount are chronic patients (6.8%); 9 have been rehabilitated (5.6%); 1 affected with a rare disease has been registered (0.6%). Although they were not mentioned in the considered sources, 105 show diagnosis of complications at birth and/or during the first year of life (66%). The percentage of premature babies with severe outcomes is thus 79%. 37 are not mentioned in any source and have had no complications (23%).
From 2007 to 2009 dead babies during the first year of life are 250 (31%); survivors are 545 (69%). 61 patients out of the total amount are chronic patients (11%), 1 of them is affected by a rare disease and registered in the Rare Disease Registry, 13 have been rehabilitated (2.3%) and 3 (0.5%) report rare diseases diagnosis on the hospital discharge record; 63 are rehabilitated (12%), 15 out of these are chronic; 11 are affected by rare diseases (2.7%), only two of which are registered in the Rare Disease Registry.
Although they were not mentioned in the considered sources, 360 report diagnosis of complications at birth and/or during the first year of life (66%). The percentage of premature babies with severe outcomes is approximately 91%. 72 are not mentioned in any source and have had no complications (13%).
CONCLUSIONS
The percentage of neonates with severe prematurity is rising remarkably in the Veneto Region due to the growth of the survival rate of babies born between 22 and 28 GW. By means of preliminary analyses, several factors related to the mother’s history, to the reproductive history and to the pregnancy course, as well as to the neonate, can apparently determine a preterm birth. In light of these preliminary data, considering the above mentioned survival and disability rates, it is particularly important to know the babies’ natural history and to verify the short and long-term clinical outcomes in terms of impact on the health care and rehabilitation planning
Clinical neurophysiology in preterm infants: a window on early phases of brain development.
Neonatal cortical auditory evoked potentials are affected by bronchopulmonary dysplasia occurring in early prematurity
Neonatal Cortical Auditory Evoked Potentials Are Affected by Clinical Conditions Occurring in Early Prematurity
Purpose: Cortical auditory evoked potentials may serve as an early indicator
of developmental problems in the auditory cortex. The aim of the study was
to determine the effect on neonatal cortical auditory processing of clinical
conditions occurring in early prematurity.
Methods: Sixty-seven preterm infants born at 29 weeks mean gestational age
(range, 23–34 weeks) were recorded at a mean postconception age of 35
weeks, before discharge from the third level neonatal intensive care unit. The
average of 330 responses to standard 1000 Hz pure tones delivered in an
oddball paradigm was recorded at frontal location. Data of 45 of 67 recruited
premature infants were available for analysis. Mean amplitudes calculated
from the data points of 30 milliseconds centered on P1 and N2 peaks in the
waveforms of each subject were measured. The effect of perinatal clinical
factors on cortical auditory evoked responses was evaluated.
Results: The amplitude of P1 component was significantly lower in infants with
bronco-pulmonary dysplasia (P 1⁄4 0.004) and retinopathy of prematurity (P 1⁄4
0.03). The multivariate analysis, done to evaluate the relative weight of
gestational age and bronco-pulmonary dysplasia and/or retinopathy of prematurity
on cortical auditory evoked potentials components, showed an effect of
clinical factors on P1 (P 1⁄4 0.005) and of gestational age on N2 (P 1⁄4 0.02).
Conclusions: Cortical auditory processing seems to be influenced by clinical
conditions complicating extremely preterm birth
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