341 - Have very preterm multiple birth infants from assisted conception increased the burden on neonatal intensive care units? A population-based study in Australia and New Zealand.

Publication Number: 341.5284

Aurelia Leung, University of New South Wales, sydney, New South Wales, Australia; Stephen Siu, University of New South Wales, Sydney, New South Wales, Australia; Temesgen Molla, UNSW, SYDNEY, New South Wales, Australia; Sharon S.W.. Chow, University of New South Wales, UNSW Sydney, New South Wales, Australia; Prudence Creighton, University of New South Wales, SYDNEY, New South Wales, Australia; Georgina M. Chambers, University of New South Wales, Kensington, New South Wales, Australia; Tim Schindler, Royal Hospital for Women, Sydney, New South Wales, Australia; Abdel-Latif Mohamed, Canberra Hospital, Canberra, Australian Capital Territory, Australia; Kei Lui, University of New South Wales, Sydney, New South Wales, Australia

Background: Increasing maternal age with declined fertility has led to a growing reliance on assisted conception (AC). In vitro fertilization is the mainstay of AC in Australia and New Zealand (ANZ), Single embryo transfer (SET) advocated in mid-2000s aim to reduce the risks and burden of very preterm birth associated with multiple births. Introduction of SET may have impacts on neonatal intensive care unit (NICU) admission volume and outcomes of very preterm infants (VPIs).

Objective: To examine ANZ NICU admission trends in multiple birth and singleton VPIs during the last 26 years, with reference to the recommendation of SET in the mid-2000s. Differences in perinatal characteristics and NICU outcomes between the AC multiple births and singletons and their SC counterparts were compared.

Design/Methods: Population-based retrospective cohort study of VPIs admitted to all ANZ NICUs during epochs of pre-SET recommendation (Epoch 1), adoption/implementation (Epoch 2) and stable/sustain period (Epoch 3) of 1995-2005, 2006-2011 and 2012-2021, respectively. Data including conception method were extracted from the Australian and New Zealand Neonatal Network registry.

Results: Of the 76,062 ANZ NICU-admitted VPIs, 9,413 AC VPIs had a higher maternal age (33.8±5.3 vs 29.3±6.1, p< 0.001) than the 66,649 SC counterparts. AC VPIs were more likely received completed antenatal steroid and delivered by Caesarean Section (CS). Number of VPIs conceived via AC admitted into ANZ NICUs is summarised in Fig 1, showing a decline of AC NICU infants from Epoch 2. Figure 2 showed the proportion of AC multiples in Epoch 1 were more than doubled that of AC singletons (left panel). From Epoch 2, there was a fall of AC multiples. The proportion of multiples continued to fall whilst AC singletons increased, resulting in an equal proportion of AC multiples and AC singletons. In contrast, the SC multiple births remained as a quarter of the SC singletons (right panel) throughout the 26 years. Controlled for confounders, multivariable analysis (Table 1) showed CS, complete antenatal steroid, and later epochs (Epoch2: AOR 0.76, 95%CI 0.70-0.82; Epoch3: 0.63, 95%CI 0.59-0.67) were independently associated lower mortality risks, while multiple births were associated with a mortality outcome regardless of AC or SC.

Conclusion(s): Reduction of AC VPI multiples with increase in AC singletons was associated with the trend to SET. The AC VPI outcomes continued to improve in parallel to SC counterparts. Efforts to reduce multiple birth would result in an overall reduced burden and a better overall NICU outcome.

Fig 1: Total Number of Very Preterm Infants Conceived via AC Admitted Into ANZ NICUs From 1995–2021
AC: assisted conception; SC: spontaneous conception; ANZ: Australia and New Zealand; NICU: neonatal intensive care unit. Epoch 1 (1995-2005) in navy is the pre-implementation period, Epoch 2 (2006-2011) in amber is during the implementation period, Epoch 3 (2012-2021) in green is the post-implementation period.

Fig 2: Proportion of AC (Left Panel) Versus SC (Right Panel) Singleton and Multiple ANZ NICU-Admitted VPIs in 1995–2021
AC: assisted conception; SC: spontaneous conception; ANZ: Australia and New Zealand; NICU: neonatal intensive care unit; VPIs: very preterm infants.

Table 1: Multivariable Logistic Regression for Mortality Across Three Epochs of AC Practice Change in Very Preterm Infants
Factors associated with increased mortality risk are highlighted in red. Factors associated with decreased mortality risk highlighted in green. AC: assisted conception; SC: spontaneous conception; SGA: small for gestational age; CS: caesarean section; S.E: standard error; AOR: adjusted odds ratio; CI: confidence interval; EPOCH1: 1995-2005, EPOCH2: 2006-2011, EPOCH3: 2012-2021.