Skip to main content
Top
Published in: BMC Pregnancy and Childbirth 1/2014

Open Access 01-12-2014 | Research article

Mortality and major morbidities in very preterm infants born from assisted conception or naturally conceived: results of the area-based ACTION study

Authors: Carlo Corchia, Monica Da Frè, Domenico Di Lallo, Luigi Gagliardi, Franco Macagno, Virgilio Carnielli, Silvana Miniaci, Marina Cuttini

Published in: BMC Pregnancy and Childbirth | Issue 1/2014

Login to get access

Abstract

Background

The use of assisted conception (AC) has been associated with higher risk of adverse perinatal outcome. Few data are available on the outcome of AC-neonates when pregnancy ends before 32 weeks of gestational age.
The aim of this study was to compare the short-term outcome of AC- and naturally conceived preterm infants <32 weeks gestation.

Methods

The area-based cohort study ACTION collected data on births 22-31 weeks gestation occurred in 2003-05 in 6 Italian regions. Infants born to 2529 mothers with known mode of conception were studied. The main outcomes were hospital mortality and survival free from major morbidities (IVH grade 3-4, cPVL, ROP stage ≥3, BPD), and were assessed separately for single and multiple infants. Other outcomes were also investigated. Multivariable logistic analyses were used to adjust for maternal and infants’ characteristics. To account for the correlation of observations within intensive care units, robust variance and standard error estimates of regression parameters were computed.

Results

AC was used in 6.4% of mothers. Infants were 2934; 314 (10.7%) were born after AC. Multiples were 86.0% among AC and 21.7% among non-AC babies. In multivariable analysis no statistically significant difference in hospital mortality and survival without major morbidities was found between AC and non-AC infants. The risk of BPD was lower in AC than in non-AC multiples (aOR 0.41, CI 0.20-0.87), and this finding did not change after controlling for mechanical ventilation (aOR 0.42, CI 0.20-0.85) or presence of a patent ductus arteriosus (aOR 0.39, CI 0.18-0.84).

Conclusion

When the analysis is restricted to very preterm infants and stratified by multiplicity, no significant associations between AC and increased risk of short-term mortality and survival without major morbidities emerge. This result is consistent with previous studies, and may confirm the hypothesis that the adverse effects of AC are mediated by preterm birth. However, larger appropriately powered studies are needed before definitely excluding the possibility of adverse events linked to AC in infants born before 32 weeks gestation.
Appendix
Available only for authorised users
Literature
2.
go back to reference Zeitlin J, Mohangoo AD, Delnord M, Cuttini M: EURO-PERISTAT Scientific Committee. The second European Perinatal Health Report: documenting changes over 6 years in the health of mothers and babies in Europe. J Epidemiol Community Health. 2013, 67: 983-985. 10.1136/jech-2013-203291.CrossRefPubMed Zeitlin J, Mohangoo AD, Delnord M, Cuttini M: EURO-PERISTAT Scientific Committee. The second European Perinatal Health Report: documenting changes over 6 years in the health of mothers and babies in Europe. J Epidemiol Community Health. 2013, 67: 983-985. 10.1136/jech-2013-203291.CrossRefPubMed
4.
go back to reference Halliday J: Outcomes of IVF conceptions: are they different?. Best Pract Res Clin Obstet Gynaecol. 2007, 21: 67-81. 10.1016/j.bpobgyn.2006.08.004.CrossRefPubMed Halliday J: Outcomes of IVF conceptions: are they different?. Best Pract Res Clin Obstet Gynaecol. 2007, 21: 67-81. 10.1016/j.bpobgyn.2006.08.004.CrossRefPubMed
5.
go back to reference Schieve LA, Cohen B, Nannini A, Ferre C, Reynolds MA, Zhang Z, Jeng G, Macaluso M, Wright WC: A population-based study of maternal and perinatal outcomes associated with assisted reproductive technology in Massachusetts. Matern Child Health J. 2007, 11: 517-525. 10.1007/s10995-007-0202-7.CrossRefPubMed Schieve LA, Cohen B, Nannini A, Ferre C, Reynolds MA, Zhang Z, Jeng G, Macaluso M, Wright WC: A population-based study of maternal and perinatal outcomes associated with assisted reproductive technology in Massachusetts. Matern Child Health J. 2007, 11: 517-525. 10.1007/s10995-007-0202-7.CrossRefPubMed
6.
go back to reference Davies MJ, Moore V, Willson K, Van Essen P, Priest K, Scott H, Haan EA, Chan A: Reproductive technologies and the risk of birth defects. N Engl J Med. 2012, 366: 1803-1813. 10.1056/NEJMoa1008095.CrossRefPubMed Davies MJ, Moore V, Willson K, Van Essen P, Priest K, Scott H, Haan EA, Chan A: Reproductive technologies and the risk of birth defects. N Engl J Med. 2012, 366: 1803-1813. 10.1056/NEJMoa1008095.CrossRefPubMed
7.
go back to reference Wen J, Jiang J, Ding C, Dai J, Liu Y, Xia Y, Liu J, Hu Z: Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis. Fertil Steril. 2012, 97: 1331-1337. 10.1016/j.fertnstert.2012.02.053.CrossRefPubMed Wen J, Jiang J, Ding C, Dai J, Liu Y, Xia Y, Liu J, Hu Z: Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis. Fertil Steril. 2012, 97: 1331-1337. 10.1016/j.fertnstert.2012.02.053.CrossRefPubMed
8.
go back to reference McDonald SD, Han Z, Mulla S, Murphy KE, Beyene J, Ohlsson A: Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol. 2009, 146: 138-148. 10.1016/j.ejogrb.2009.05.035.CrossRefPubMed McDonald SD, Han Z, Mulla S, Murphy KE, Beyene J, Ohlsson A: Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol. 2009, 146: 138-148. 10.1016/j.ejogrb.2009.05.035.CrossRefPubMed
9.
go back to reference McDonald SD, Han Z, Mulla S, Ohlsson A, Beyene J, Murphy KE: Preterm birth and low birth weight among in vitro fertilization twins: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol. 2010, 148: 105-113. 10.1016/j.ejogrb.2009.09.019.CrossRefPubMed McDonald SD, Han Z, Mulla S, Ohlsson A, Beyene J, Murphy KE: Preterm birth and low birth weight among in vitro fertilization twins: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol. 2010, 148: 105-113. 10.1016/j.ejogrb.2009.09.019.CrossRefPubMed
10.
go back to reference Stewart JE, Allred EN, Collins M, Abbott J, Leviton A, Paneth N, Reuss ML, Susser M, Hegyi T, Hiatt M, Sanocka U, Shahrivar F, Van Marter L, Banogan P, Genest D, Heller D, Shen-Schwarz S, Dammann O, Kuban KCK, Pagano M: Risk of cranial ultrasound abnormalities in very-low-birth-weight infants conceived with assisted reproductive techniques. J Perinatol. 2002, 22: 37-45. 10.1038/sj.jp.7210666.CrossRefPubMed Stewart JE, Allred EN, Collins M, Abbott J, Leviton A, Paneth N, Reuss ML, Susser M, Hegyi T, Hiatt M, Sanocka U, Shahrivar F, Van Marter L, Banogan P, Genest D, Heller D, Shen-Schwarz S, Dammann O, Kuban KCK, Pagano M: Risk of cranial ultrasound abnormalities in very-low-birth-weight infants conceived with assisted reproductive techniques. J Perinatol. 2002, 22: 37-45. 10.1038/sj.jp.7210666.CrossRefPubMed
11.
go back to reference Hashimoto LN, Lindsell CJ, Brewer DE, Eichel MM, Donovan EF: Contributions of infertility treatment to very-low-birth-weight multiple birth infants receiving neonatal intensive care. Am J Obstet Gynecol. 2004, 190: 401-406. 10.1016/j.ajog.2003.07.026.CrossRefPubMed Hashimoto LN, Lindsell CJ, Brewer DE, Eichel MM, Donovan EF: Contributions of infertility treatment to very-low-birth-weight multiple birth infants receiving neonatal intensive care. Am J Obstet Gynecol. 2004, 190: 401-406. 10.1016/j.ajog.2003.07.026.CrossRefPubMed
12.
go back to reference Schimmel MS, Hammerman C, Lusky A, Reichman B: Very low-birth-weight-infants conceived by in vitro fertilization are not at higher risk for mortality and morbidity: a population-based study. Fertil Steril. 2006, 85: 907-912. 10.1016/j.fertnstert.2005.09.050.CrossRefPubMed Schimmel MS, Hammerman C, Lusky A, Reichman B: Very low-birth-weight-infants conceived by in vitro fertilization are not at higher risk for mortality and morbidity: a population-based study. Fertil Steril. 2006, 85: 907-912. 10.1016/j.fertnstert.2005.09.050.CrossRefPubMed
13.
go back to reference Messerschimdt A, Olischar M, Bimbacher R, Weber M, Pollack A, Leitich H: Perinatal outcome of preterm infants <1500 g after IVF pregnancies compared with natural conception. Arch Dis Child Fetal Neonatal Ed. 2010, 95: F225-F229. 10.1136/adc.2009.165761.CrossRef Messerschimdt A, Olischar M, Bimbacher R, Weber M, Pollack A, Leitich H: Perinatal outcome of preterm infants <1500 g after IVF pregnancies compared with natural conception. Arch Dis Child Fetal Neonatal Ed. 2010, 95: F225-F229. 10.1136/adc.2009.165761.CrossRef
14.
go back to reference Shah V, AlWassia H, Shah K, Yoon W, Shah P: Neonatal outcomes among multiple births in ≤32 weeks gestational age: does mode of conception have an impact? a cohort study. BMC Pediatrics. 2011, 11: 54-10.1186/1471-2431-11-54.CrossRefPubMedPubMedCentral Shah V, AlWassia H, Shah K, Yoon W, Shah P: Neonatal outcomes among multiple births in ≤32 weeks gestational age: does mode of conception have an impact? a cohort study. BMC Pediatrics. 2011, 11: 54-10.1186/1471-2431-11-54.CrossRefPubMedPubMedCentral
15.
go back to reference Picaud JC, Chalies S, Combes C, Mercier G, Dechaud H, Cambonie G: Neonatal mortality and morbidity in preterm infants born from assisted reproductive technologies. Acta Paediatr. 2012, 101: 846-851. 10.1111/j.1651-2227.2012.02713.x.CrossRefPubMed Picaud JC, Chalies S, Combes C, Mercier G, Dechaud H, Cambonie G: Neonatal mortality and morbidity in preterm infants born from assisted reproductive technologies. Acta Paediatr. 2012, 101: 846-851. 10.1111/j.1651-2227.2012.02713.x.CrossRefPubMed
16.
go back to reference Tallandini MA, Morsan V, Macagno F: Preterm birth and assisted reproductive techniques/ART: maternal emotional wellbeing and quality of mother-infant interaction during the first three months of life. Early Hum Dev. 2012, 88: 397-402. 10.1016/j.earlhumdev.2011.10.003.CrossRefPubMed Tallandini MA, Morsan V, Macagno F: Preterm birth and assisted reproductive techniques/ART: maternal emotional wellbeing and quality of mother-infant interaction during the first three months of life. Early Hum Dev. 2012, 88: 397-402. 10.1016/j.earlhumdev.2011.10.003.CrossRefPubMed
18.
go back to reference Papiernik E, Zeitlin J, Delmas D, Blondel B, Künzel W, Cuttini M, Weber T, Petrou S, Gortner L, Kollée L, Draper ES, MOSAIC Group: Differences in outcome between twins and singletons born very preterm: results from a population-based European cohort. Hum Reprod. 2010, 25: 1035-1043. 10.1093/humrep/dep430.CrossRefPubMed Papiernik E, Zeitlin J, Delmas D, Blondel B, Künzel W, Cuttini M, Weber T, Petrou S, Gortner L, Kollée L, Draper ES, MOSAIC Group: Differences in outcome between twins and singletons born very preterm: results from a population-based European cohort. Hum Reprod. 2010, 25: 1035-1043. 10.1093/humrep/dep430.CrossRefPubMed
19.
go back to reference McElrath TF, Hecht JL, Dammann O, Boggess K, Onderdonk A, Markenson G, Harper M, Delpapa E, Allred EN, Leviton A: Pregnancy disorders that lead to delivery before the 28th week of gestation: an epidemiologic approach to classification. Am J Epidemiol. 2008, 168: 980-989. 10.1093/aje/kwn202.CrossRefPubMedPubMedCentral McElrath TF, Hecht JL, Dammann O, Boggess K, Onderdonk A, Markenson G, Harper M, Delpapa E, Allred EN, Leviton A: Pregnancy disorders that lead to delivery before the 28th week of gestation: an epidemiologic approach to classification. Am J Epidemiol. 2008, 168: 980-989. 10.1093/aje/kwn202.CrossRefPubMedPubMedCentral
20.
go back to reference Zhang J, Merialdi M, Platt LD, Kramer MS: Defining normal and abnormal fetal growth: promises and challenges. Am J Obstet Gynecol. 2010, 202: 522-528. 10.1016/j.ajog.2009.10.889.CrossRefPubMedPubMedCentral Zhang J, Merialdi M, Platt LD, Kramer MS: Defining normal and abnormal fetal growth: promises and challenges. Am J Obstet Gynecol. 2010, 202: 522-528. 10.1016/j.ajog.2009.10.889.CrossRefPubMedPubMedCentral
21.
go back to reference Ancel P-Y, Marret S, Larroque B, Arnaud C, Zupan-Simunek V, Voyer M, Rozé J-C, Matis J, Burguet A, Ledésert B, André M, Pierrat V, Kaminski M, Epipage Study Group: Are maternal hypertension and small-for-gestational age risk factors for severe intraventricular hemorrhage and cystic periventricular leukonalacia? results of the EPIPAGE cohort study. Am J Obstet Gynecol. 2005, 193: 178-184. 10.1016/j.ajog.2004.11.057.CrossRefPubMed Ancel P-Y, Marret S, Larroque B, Arnaud C, Zupan-Simunek V, Voyer M, Rozé J-C, Matis J, Burguet A, Ledésert B, André M, Pierrat V, Kaminski M, Epipage Study Group: Are maternal hypertension and small-for-gestational age risk factors for severe intraventricular hemorrhage and cystic periventricular leukonalacia? results of the EPIPAGE cohort study. Am J Obstet Gynecol. 2005, 193: 178-184. 10.1016/j.ajog.2004.11.057.CrossRefPubMed
22.
go back to reference Papile LA, Burstein J, Burstein R, Koffler H: Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978, 92: 529-534. 10.1016/S0022-3476(78)80282-0.CrossRefPubMed Papile LA, Burstein J, Burstein R, Koffler H: Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978, 92: 529-534. 10.1016/S0022-3476(78)80282-0.CrossRefPubMed
23.
go back to reference de Vries LS: Neurological assessment of the preterm infant. Acta Paediatr. 1996, 85: 765-771. 10.1111/j.1651-2227.1996.tb14149.x.CrossRefPubMed de Vries LS: Neurological assessment of the preterm infant. Acta Paediatr. 1996, 85: 765-771. 10.1111/j.1651-2227.1996.tb14149.x.CrossRefPubMed
24.
go back to reference Walsh MC, Kliegman RM: Review necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am. 1986, 33: 179-201.PubMed Walsh MC, Kliegman RM: Review necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am. 1986, 33: 179-201.PubMed
25.
go back to reference Williams RL: A note on robust variance estimation for cluster-correlated data. Biometrics. 2000, 56: 645-646. 10.1111/j.0006-341X.2000.00645.x.CrossRefPubMed Williams RL: A note on robust variance estimation for cluster-correlated data. Biometrics. 2000, 56: 645-646. 10.1111/j.0006-341X.2000.00645.x.CrossRefPubMed
26.
go back to reference Hsieh FY, Block DA, Larsen MD: A simple method of sample size calculation for linear and logistic regression. Stat Med. 1998, 17: 1623-1634. 10.1002/(SICI)1097-0258(19980730)17:14<1623::AID-SIM871>3.0.CO;2-S.CrossRefPubMed Hsieh FY, Block DA, Larsen MD: A simple method of sample size calculation for linear and logistic regression. Stat Med. 1998, 17: 1623-1634. 10.1002/(SICI)1097-0258(19980730)17:14<1623::AID-SIM871>3.0.CO;2-S.CrossRefPubMed
27.
go back to reference Kalra SK, Molinaro TA: The association of in vitro fertilization and perinatal morbidity. Semin Reprod Med. 2008, 26: 423-425. 10.1055/s-0028-1087108.CrossRefPubMed Kalra SK, Molinaro TA: The association of in vitro fertilization and perinatal morbidity. Semin Reprod Med. 2008, 26: 423-425. 10.1055/s-0028-1087108.CrossRefPubMed
28.
go back to reference Williams C, Sutcliffe A: Infant outcomes of assisted reproduction. Early Hum Dev. 2009, 85: 673-677. 10.1016/j.earlhumdev.2009.08.055.CrossRefPubMed Williams C, Sutcliffe A: Infant outcomes of assisted reproduction. Early Hum Dev. 2009, 85: 673-677. 10.1016/j.earlhumdev.2009.08.055.CrossRefPubMed
29.
go back to reference Pinborg A, Wennerholm UB, Romundstad LB, Loft A, Aittomaki K, Soderstrom-Anttila V, Nygren KG, Hazekamp J, Bergh C: Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? systematic review and meta-analysis. Hum Reprod Update. 2013, 19: 87-104. 10.1093/humupd/dms044.CrossRefPubMed Pinborg A, Wennerholm UB, Romundstad LB, Loft A, Aittomaki K, Soderstrom-Anttila V, Nygren KG, Hazekamp J, Bergh C: Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? systematic review and meta-analysis. Hum Reprod Update. 2013, 19: 87-104. 10.1093/humupd/dms044.CrossRefPubMed
30.
go back to reference Romundstad LB, Romundstad PR, Sunde A, von Düring V, Skjærven R, Gunnell D, Vatten LJ: Effects of technology or maternal factors on perinatal outcome after assisted fertilisation: a population-based cohort study. Lancet. 2008, 372: 737-743. 10.1016/S0140-6736(08)61041-7.CrossRefPubMed Romundstad LB, Romundstad PR, Sunde A, von Düring V, Skjærven R, Gunnell D, Vatten LJ: Effects of technology or maternal factors on perinatal outcome after assisted fertilisation: a population-based cohort study. Lancet. 2008, 372: 737-743. 10.1016/S0140-6736(08)61041-7.CrossRefPubMed
31.
go back to reference Boulet SL, Schieve LA, Nannini A, Ferre C, Devine O, Cohen B, Zhang Z, Wright V, Macaluso M: Perinatal outcomes of twin births conceived using assisted reproduction technology: a population-based study. Hum Reprod. 2008, 23: 1941-1948. 10.1093/humrep/den169.CrossRefPubMed Boulet SL, Schieve LA, Nannini A, Ferre C, Devine O, Cohen B, Zhang Z, Wright V, Macaluso M: Perinatal outcomes of twin births conceived using assisted reproduction technology: a population-based study. Hum Reprod. 2008, 23: 1941-1948. 10.1093/humrep/den169.CrossRefPubMed
32.
go back to reference Corchia C, Mastroiacovo P: Health promotion in children, mothers and families: here’s why we should “think about it before conception”. Ital J Pediatr. 2013, 39: 68-10.1186/1824-7288-39-68. epub ahead of printCrossRefPubMedPubMedCentral Corchia C, Mastroiacovo P: Health promotion in children, mothers and families: here’s why we should “think about it before conception”. Ital J Pediatr. 2013, 39: 68-10.1186/1824-7288-39-68. epub ahead of printCrossRefPubMedPubMedCentral
33.
go back to reference Gagliardi L, Rusconi F, Da Frè M, Mello G, Carnielli V, Di Lallo D, Macagno F, Miniaci S, Corchia C, Cuttini M: Pregnancy disorders leading to very preterm birth influence neonatal outcomes: results of the population-based ACTION cohort study. Pediatr Res. 2013, 73: 794-801. 10.1038/pr.2013.52.CrossRefPubMed Gagliardi L, Rusconi F, Da Frè M, Mello G, Carnielli V, Di Lallo D, Macagno F, Miniaci S, Corchia C, Cuttini M: Pregnancy disorders leading to very preterm birth influence neonatal outcomes: results of the population-based ACTION cohort study. Pediatr Res. 2013, 73: 794-801. 10.1038/pr.2013.52.CrossRefPubMed
34.
go back to reference Corchia C, Ferrante P, Da Frè M, Di Lallo D, Gagliardi L, Carnielli V, Miniaci S, Piga S, Macagno F, Cuttini M: Cause-specific mortality of very preterm infants and antenatal events. J Pediatr. 2013, 162: 1125-1132. 10.1016/j.jpeds.2012.11.093.CrossRefPubMed Corchia C, Ferrante P, Da Frè M, Di Lallo D, Gagliardi L, Carnielli V, Miniaci S, Piga S, Macagno F, Cuttini M: Cause-specific mortality of very preterm infants and antenatal events. J Pediatr. 2013, 162: 1125-1132. 10.1016/j.jpeds.2012.11.093.CrossRefPubMed
35.
go back to reference Helmerhorst FM, Perquin DA, Donker D, Keirse MJ: Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ. 2004, 328: 261-10.1136/bmj.37957.560278.EE.CrossRefPubMedPubMedCentral Helmerhorst FM, Perquin DA, Donker D, Keirse MJ: Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ. 2004, 328: 261-10.1136/bmj.37957.560278.EE.CrossRefPubMedPubMedCentral
36.
go back to reference Pandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A: Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update. 2012, 18: 485-503. 10.1093/humupd/dms018.CrossRefPubMed Pandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A: Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update. 2012, 18: 485-503. 10.1093/humupd/dms018.CrossRefPubMed
Metadata
Title
Mortality and major morbidities in very preterm infants born from assisted conception or naturally conceived: results of the area-based ACTION study
Authors
Carlo Corchia
Monica Da Frè
Domenico Di Lallo
Luigi Gagliardi
Franco Macagno
Virgilio Carnielli
Silvana Miniaci
Marina Cuttini
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2014
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/1471-2393-14-307

Other articles of this Issue 1/2014

BMC Pregnancy and Childbirth 1/2014 Go to the issue