Journal of the New Zealand Medical Association, 14-December-2007, Vol 120 No 1267
Neonatal intensive care utilisation by infants born to mothers older than 40 years of age: a 10-year review
Malcolm Battin, Coila Bevan, David Knight
Over the last 25 years a combination of social and demographic factors have resulted in a notable drift upwards in the age at which women in developed countries give birth to their children. In New Zealand, for the first quarter of 2006, the median maternal age at birth was 30.4 years compared with 28.7 years in 1996 and 25.1 years in 1975.1 Consequently, a large number of women are having first babies in their mid-30s and a significant number are having their first babies at age 40 or older. Indeed, at National Women’s Hospital (Auckland, New Zealand) approximately 3% of deliveries are to women over 40 years old.2 Although most women over the age of 35 or even over 40 have healthy pregnancies and healthy babies, there are potential problems associated with pregnancy at an increased maternal age. These include declining fertility, and an increased rate of multiple pregnancies; spontaneous pregnancy loss; medical complications of pregnancy; intrauterine growth restriction; and prematurity and congenital anomalies, including chromosomal abnormality.
Moreover, at the time of the labour and delivery, increased maternal age is associated with higher risk of fetal distress, prolonged second stage of labour, and increased rates of Caesarean section.3–5 These factors (either alone or in combination) may result in both short- and long-term neonatal morbidity.
While there is a reasonable body of literature regarding the effect of advanced maternal age on obstetric outcome (including perinatal mortality), there is a relative paucity of data on neonatal outcome, which is often restricted to neonatal admission rate.5–7 In one large study of births in California in the early 1990s an increase in the proportion of infants coded as having any birth asphyxia was reported following birth to nulliparous women over 40 years but a lower rate of birth trauma was also reported perhaps due to increased delivery by caesarean section.8 Moreover, there are few published series of temporal trends in utilisation of neonatal resources by infants born to women of very advanced maternal age.
Therefore the aims of this study were two-fold. Firstly, to quantify the requirement for neonatal intensive care in infants born to women aged 40 years old or over during the period 1995–2004 inclusive. Secondly, to evaluate trends in: demographic characteristics; neonatal mortality; neonatal morbidity; and service utilisation, measured by duration of respiratory support and stay on the neonatal unit.
Data were reviewed for the 10-year period January 1995 to December 2004. All infants admitted to National Women’s Hospital Neonatal Intensive Care Unit (NICU) and eligible for registration with the Australian New Zealand Neonatal Network (ANZNN) were identified from the National Women’s NICU database. The ANZNN registration criteria included live born infants transferred from labour ward or admitted to the participating hospital at less than 28 days of age with any of the following: birth at less than 32 weeks gestation; birth weight less than 1500 grams; more than 4 consecutive hours of respiratory support, or major neonatal surgery.
Ethical approval has previously been obtained for the submission of de-identified data to the ANZNN from our hospital. For the time period reviewed, National Women’s Hospital (NWH) provided all neonatal intensive care to the central and Northern Auckland region which included approximately 12,000 births annually.
The number of infants born to mothers in the age group of interest was determined then appropriate clinical and demographic data were reviewed. The dataset included a de-identified record of maternal age; ethnicity, and past pregnancy history (including previous premature births), previous perinatal death, and assisted conception.
Pregnancy data included plurality, presenting antenatal problem, prolonged rupture of membranes, preterm labour, intrauterine growth restriction (suspected antenatal), antenatal diagnosis of fetal malformation, hypertension in pregnancy, antepartum haemorrhage, antenatal corticosteroids, and (for multiples) birth order.
Delivery data comprised of presentation and mode of delivery. Neonatal data—comprising gestational age, birth weight, Apgar scores, resuscitation details, and respiratory diagnosis—measures morbidity including highest lowest fractional inspired oxygen (FiO2) in the first 12 hours, exogenous surfactant use, air leak, days on positive pressure ventilation, days on continuous positive airways pressure (CPAP), proven or suspected necrotising enterocolitis (NEC), number of proven infections, intraventricular haemorrhage (IVH), or other cranial ultrasound abnormality and retinopathy of prematurity (ROP).
Important trends in both overall numbers of infants and individual morbidities were examined. Data are presented as mean and standard deviation if normally distributed, or as median and range if not normally distributed. The data are presented by year or if more appropriate by 2- or 5-year epoch.
To demonstrate trends in graphs or tables (for total number of infants, percentage of admissions, number of twins, deaths, days of NICU care, and percentage of respiratory support) the epochs are 2-year blocks. The two items of data that were used to indicate utilisation of neonatal resources were total days hospital care prior to discharge and total days on respiratory support during neonatal stay.
To explore differences in demographic and presenting obstetric clinical data, the infants were divided into two time periods (1995–1999 and 2000–2004) and the data compared. Incidences were compared by Chi-squared and continuous data by Mann Whitney U test or Student’s t-test as appropriate. Statistics were calculated using Statview (Cary, NC USA) software.
For the study period, 203 babies (who fulfilled ANZNN registration criteria following birth to women older than 40 years) were admitted to NICU at National Women’s Hospital. The presenting obstetric clinical data and delivery mode are summarised Table 1.
Table 1. Antenatal complications and mode of delivery for mothers aged 40 years and over (registered with Australian New Zealand Neonatal Network) delivering babies in 1995–2004
On examining the data for trends in antenatal complications there was an increase in the proportion of pregnancies coded as complicated by suspected intrauterine growth restriction for 1995–1999 versus 2000–2004 (8% versus 14%, p=0.02) and in the proportion reported to have spontaneous preterm labour (16% versus 39%, p=0.03) but no other significant differences or trends in antenatal characteristics were detected.
There was no statistically significant difference in mode of delivery between the two time periods 1995–1999 and 2000–2004. Overall, there was a high rate of antenatal steroid use in pregnancies that delivered prior to 34 completed weeks of gestation, with 100 of the 116 (62%) receiving a full course and 72 of 116 (86%) receiving some steroid prior to birth.
The median (range) gestational age and birth weight for the infants were 33 (24–42) weeks and 2092 (570–5320) grams respectively. Although there was wide variation in the range of values for the individual years there was no clear trend by individual year or 5-year block in either gestational age or birth weight. Overall, the majority of infants were born in satisfactory condition with a median (range) Apgar score of 7 (1–9) at 1 minute and 9 (1–10) at 5 minutes respectively.
Indeed, only 80 infants (39%) and 24 infants (12%) had an Apgar score below 7 at 1 and 5 minutes respectively. Resuscitation at birth included intubation in 15.3% of infants. After admission to the neonatal unit, 33/203 (16%) received surfactant for respiratory distress syndrome.
In addition, one infant with meconium aspiration syndrome received high frequency oscillation ventilation, five infants with pulmonary hypertension received nitric oxide, and one infant with cardiac malformation underwent extracorporeal membrane oxygenation (ECMO). There were no significant trends in the proportion of infants requiring these interventions over time.
Mortality and acquired morbidities with long-term serious consequences were uncommon. Eleven of the 203 (5.4%) infants died. There was no overall trend in death when examined by individual year and no significant difference in rate between the first and second time periods.
Neonatal morbidity included four infants with air leak requiring drainage and eight infants diagnosed as having chronic lung disease ( five of these were discharged home receiving supplemental oxygen). Also four infants had acquired neurological conditions that adversely affected outcome. Specifically, there were two term infants with severe neonatal encephalopathy that died and two preterm infants (25 and 28 weeks gestation) with major (i.e. grade III/IV) intraventricular haemorrhage (IVH).
The infant with grade IV IVH died and the other who had grade III survived. Other serious neonatal morbidity were uncommon; the median number of proven infections was 0 (range 0–2), there was only one proven and one suspected case of necrotising enterocolitis, and no cases of retinopathy of prematurity (ROP) requiring treatment. Given the rarity of these morbidities, trends were not assessed.
In addition to the acquired morbidity, several infants had chromosomal abnormality, dysmorphic syndromes, or congenital anomalies that would potentially affect outcome. Seven infants had major chromosomal abnormality, this included Trisomy 21 in six infants and Trisomy 18 in one infant. Three infants were diagnosed with an abnormal syndrome in the neonatal period; one each of Prader Willi syndrome, Noonan syndrome, and Klinefelter syndrome. In addition, nine infants had major congenital anomalies including five with cardiac lesions and two each with skeletal or central nervous system anomalies.
The five cardiac malformations included transposition of the great arteries (TGA) in three cases, hypoplastic right heart ventricle in one, and ventriculo-septal defect (VSD) in one. The two skeletal malformations were missing digits from the hand in one case and syndactyly in the other. The two malformations of the central nervous system were idiopathic microcephaly and an occipital encephalocoele.
Important trends—including: total number of infants, percentage of admissions, number of twins, deaths, days of NICU care, and percentage of respiratory support—are summarised in Table 2.
The overall mean duration of neonatal admission was 32 days. An increase was observed in the number of admissions, total days NICU care, and percentage of total respiratory support from 1995–6 to a peak in 2001–2. Thereafter there was a small decrease in numbers but there were changes in referral practice at that time, with the opening of other level two neonatal units in the city.
Assisted conception, as recorded in the database (i.e. reported by the women or lead maternity caregiver), was significantly more common in the mothers over 40 years compared with those below 40 years of age (15% versus 6.7%, p<0.001). Moreover, for infants born to mothers over 40 and admitted to NICU, there was an increase in the proportion reported to be conceived following assisted conception from approximately 9% and 13% for the two time periods 1995–1999 and 2000–2004.
Changes in the contribution from the major ethnic groups over time are presented in Figure 1. A rise was seen in number of New Zealand European infants compared to stable numbers in the other ethnic groups.
Table 2. Summary of neonatal admissions and care in infants born to women over 40 years old for the 10-year period 1995–2004
BW=birth weight; GA=gestational age; *2004 had referral process changes with opening of other level 2 neonatal units.
Figure 1. Trends in the number of infants born to mothers over 40 years of age, by ethnic group
NZ Euro=New Zealand European; PI=Pacific Islander (e.g. Samoan, Tongan, Niuean, Cook Islander).
New Zealand, like many other developed countries, has experienced a substantial increase in births to women over the age of 40 years. For instance, over the last 10 years, National Women’s Hospital has experienced an increase in deliveries to women in this age group from 1.5% to approximately 3% of total deliveries.2
It is well recognised that with increasing maternal age several factors (including increased rates of multiple births, medical complications of pregnancy, and perinatal complications) result in more infants with neonatal problems. This study examined trends over a 10-year period in a single centre and demonstrated an increase in both the absolute number of admissions and proportion of total admissions born to women aged over 40 years.
Although there have been concomitant changes in the rates of delivery to older women and some changes the total number of admissions for neonatal intensive care, it is notable that infants born to women over the age of 40 account for 3% of deliveries but 5% of neonatal admissions. Further, these demographic changes are associated with a significant increase in the workload measured by total days neonatal care and total time on respiratory support for this group of infants.
Despite the increase in birth numbers to women in the over-40s age group, the presenting obstetric factors and infant characteristics were fairly consistent. Specifically, the rates of prolonged rupture of membranes, antepartum haemorrhage, hypertension in pregnancy, or fetal distress were unchanged but there was a significant increase in multiple pregnancy, spontaneous preterm labour, and suspected intrauterine growth restriction (IUGR)—although the majority of the infants were neither extremely low gestational age nor extremely low birth weight, with a median gestational age and birth weight of 33 weeks and 2092 grams respectively.
The significant increase in multiple pregnancy may contribute to the increase in premature birth. Also the increased IUGR rate may be explained by better ultrasound detection and the use of individualized growth charts.9,10
Even though the neonatal mortality and rate of serious neonatal morbidities were both low, the admission for neonatal care is not without consequence. Certainly the infants did receive a substantial amount of respiratory support and the mean duration of neonatal admission was 32 days. Interestingly, overall 16% got surfactant (to aid lung function) with no significant change in rates between two time periods. Finally with respect to the individual infant there is recent evidence that even if only moderately premature there can be significant short term morbidity11 and in the longer term this may be associated with some cognitive impairment compared with matched controls.12
The increase in numbers of infants receiving neonatal intensive care following birth to women above the age of 40 years occurs predominately in NZ Europeans. Full discussion of the complex social factors responsible for the increasing maternal age is beyond the scope of this paper. However, it is noted that Māori mothers tend to be younger with a median age at birth of 26.0 years compared with 30.4 years in the overall population 2006.1 It is also clear that increased maternal age is associated with difficulty conceiving and increased rates of assisted conception.
Overall, 15% of the infants born to the older mothers were reported to be the product of assisted conception. Furthermore, it is possible that this was an underestimate of fertility treatment data as information may not be forthcoming or not recorded at the time of pregnancy booking. However, a steady increase in numbers was observed through the 10-year period. Twin births following fertility treatment are at an increased risk of preterm birth, but are mostly mildly preterm.13
In the study group, an increase in twins as both absolute numbers and proportion of total admissions was seen with a peak in 2002. The pattern for the reported use of fertility treatment and the rate of twin birth were similar with an initial increases then, after 2002, a decline in rate seen for both.
Although spontaneous twins are more common with advanced maternal age, the recent decline in the twin rate almost certainly reflects changes in fertility practice. Since 2004, or perhaps slightly earlier, there has been a push for single embryo transfer.14
A potential limitation of the study is that it is from a single centre. Certainly the apparent decrease in overall numbers after 2003 may be a consequence of changes in neonatal admissions, as two other level two neonatal units opened in the city.
Our hospital also possibly selects a greater proportion of older women and the increased neonatal admission rate may not reflect the general experience in New Zealand. However, this is unlikely that our unit is the only one affected by these demographic changes given the national population data illustrating an increase in the number of women who are now giving birth to children after the age of 40. Nevertheless, further work is planned using ANZNN data on all New Zealand admissions which will allow the study of trends for the whole country rather than a single centre.
A second potential limitation of the study is that there have been significant changes in neonatal respiratory care during the 10-year period 1995–2004. Firstly, the increasing availability and use of surfactant from the mid 1990s then increased CPAP use and a decline in both ventilation and surfactant use in the late 1990s. In order to account for these changes, the data on trends in respiratory support (Table 2) are calculated from total time on respiratory support, i.e. calculated from combined ventilation and CPAP duration.
In conclusion, infants born to mothers over the age of 40 years currently represent about 5% of admissions to the service fulfilling ANZNN criteria. Their mortality and morbidity is fairly low, but admission numbers and service utilisation (measured by total days care and respiratory support) has markedly increased compared to 1995. Although the number of infants remains quite low this increase in neonatal workload and change in maternal demographics needs to be recognised and may have implications for service planning.
Competing interests: None.
Author information: Malcolm Battin, Senior Lecturer (Neonatology)1,2; Coila Bevan Research Nurse2; David Knight, Clinical Director of Newborn Services2;
Correspondence: MR Battin, Newborn Services, National Women’s Health, 9th Floor Support Building, Auckland City Hospital, Private Bag 92 189, Auckland, New Zealand. Fax: +64 (0)9 6309753; email: firstname.lastname@example.org
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