A Retrospective Cohort Study on Mortality and Neurodevelopmental Outcomes of Preterm Very Low Birth Weight Infants Born to Mothers with Hypertensive Disorders of Pregnancy

Abstract Objective We examined the effects of maternal hypertensive disorders of pregnancy (HDP) on the mortality and neurodevelopmental outcomes in preterm very low birth weight (VLBW) infants (BW ≤1,500 g) based on their intrauterine growth status and gestational age (GA). Study Design We included singleton VLBW infants born at <32 weeks' gestation registered in the Neonatal Research Network Japan database. The composite outcomes including death, cerebral palsy (CP), and developmental delay (DD) at 3 years of age were retrospectively compared among three groups: appropriate for GA (AGA) infants of mothers with and without HDP (H-AGA and N-AGA) and small for GA (SGA) infants of mothers with HDP (H-SGA). The adjusted odds ratios (AOR) and 95% confidence intervals (CI) stratified by the groups of every two gestational weeks were calculated after adjusting for the center, year of birth, sex, maternal age, maternal diabetes, antenatal steroid use, clinical chorioamnionitis, premature rupture of membranes, non-life-threatening congenital anomalies, and GA. Results Of 19,323 eligible infants, outcomes were evaluated in 10,192 infants: 683 were H-AGA, 1,719 were H-SGA, and 7,790 were N-AGA. Between H-AGA and N-AGA, no significant difference was observed in the risk for death, CP, or DD in any GA groups. H-AGA had a lower risk for death, CP, or DD than H-SGA in the 24 to 25 weeks group (AOR: 0.434, 95% CI: 0.202–0.930). The odds for death, CP, or DD of H-SGA against N-AGA were found to be higher in the 24 to 25 weeks (AOR: 2.558, 95% CI: 1.558–3.272) and 26 to 27 weeks (AOR: 1.898, 95% CI: 1.427–2.526) groups, but lower in the 30 to 31 weeks group (AOR: 0.518, 95% CI: 0.335–0.800). Conclusion There was a lack of follow-up data; however, the outcomes of liveborn preterm VLBW infants of mothers with HDP depended on their intrauterine growth status and GA at birth. Key Points The effects of HDP on preterm low birth weight infants need to be further examined. The outcomes were not different between AGA infants with and without maternal HDP. The outcomes of SGA infants with maternal HDP were dependent on their GA.

[1]  Reint K Jellema,et al.  Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key , 2020, Cells.

[2]  A. Wilcox,et al.  Association of Preeclampsia in Term Births With Neurodevelopmental Disorders in Offspring. , 2020, JAMA psychiatry.

[3]  B. Mol,et al.  Impact of Hypertension and Preeclampsia Intervention Trial At Near Term‐I (HYPITAT‐I) on obstetric management and outcome in The Netherlands , 2020, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[4]  Neena Modi,et al.  Association of early postnatal transfer and birth outside a tertiary hospital with mortality and severe brain injury in extremely preterm infants: observational cohort study with propensity score matching , 2019, BMJ.

[5]  J. Limpens,et al.  Early‐onset fetal growth restriction: A systematic review on mortality and morbidity , 2019, Acta obstetricia et gynecologica Scandinavica.

[6]  P. Albert,et al.  Fetal Growth Patterns in Pregnancy-Associated Hypertensive Disorders: NICHD Fetal Growth Studies. , 2019, American journal of obstetrics and gynecology.

[7]  P. Shah,et al.  Outcomes of singleton small for gestational age preterm infants exposed to maternal hypertension: a retrospective cohort study , 2019, Pediatric Research.

[8]  L. Gagliardi,et al.  Maternal hypertension and survival in singletons and twins born at 23–29 weeks: not just one answer… , 2019, Pediatric Research.

[9]  Kiyoko Kato,et al.  Neurodevelopmental Outcomes in Infants With Birth Weight ≤500 g at 3 Years of Age , 2018, Pediatrics.

[10]  P. Kearney,et al.  Association of Hypertensive Disorders of Pregnancy With Risk of Neurodevelopmental Disorders in Offspring: A Systematic Review and Meta-analysis , 2018, JAMA psychiatry.

[11]  P. Lumbiganon,et al.  The global epidemiology of preterm birth. , 2018, Best practice & research. Clinical obstetrics & gynaecology.

[12]  H. McConachie,et al.  Cognitive outcome in childhood of birth weight discordant monochorionic twins: the long-term effects of fetal growth restriction , 2018, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[13]  G. Badger,et al.  Maternal Hypertension and Mortality in Small for Gestational Age 22- to 29-Week Infants , 2018, Reproductive Sciences.

[14]  M. Geraci,et al.  Morbidity and Mortality in Small for Gestational Age Infants at 22 to 29 Weeks’ Gestation , 2018, Pediatrics.

[15]  L. Doyle,et al.  Reporting Outcomes of Extremely Preterm Births , 2016, Pediatrics.

[16]  R. Mori,et al.  Hypertensive disorders of pregnancy and outcomes of preterm infants of 24 to 28 weeks’ gestation , 2016, Journal of Perinatology.

[17]  K. Kawakami,et al.  Impact of pre‐eclampsia in extremely premature infants: Population‐based study , 2016, Pediatrics international : official journal of the Japan Pediatric Society.

[18]  O. Iwata,et al.  Developmental assessment of VLBW infants at 18months of age: A comparison study between KSPD and Bayley III , 2016, Brain and Development.

[19]  A. Papageorghiou,et al.  Consensus definition of fetal growth restriction: a Delphi procedure , 2016, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[20]  N. Winer,et al.  Cause of Preterm Birth as a Prognostic Factor for Mortality , 2016, Obstetrics and gynecology.

[21]  M. Bickle Graz,et al.  Being Small for Gestational Age: Does it Matter for the Neurodevelopment of Premature Infants? A Cohort Study , 2015, PloS one.

[22]  Cassandra N. Spracklen,et al.  Effects of smoking and preeclampsia on birth weight for gestational age , 2015, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[23]  J. Eriksson,et al.  Maternal hypertensive pregnancy disorders and cognitive functioning of the offspring: a systematic review. , 2014, Journal of the American Society of Hypertension : JASH.

[24]  E. Abalos,et al.  Pre‐eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health , 2014, BJOG : an international journal of obstetrics and gynaecology.

[25]  B. Vohr Neurodevelopmental outcomes of extremely preterm infants. , 2014, Clinics in perinatology.

[26]  N. Yonemoto,et al.  Outcomes of Infants Born at 22 and 23 Weeks’ Gestation , 2013, Pediatrics.

[27]  Kazushi Watanabe,et al.  Outline of Definition and Classification of “Pregnancy induced Hypertension (PIH)” , 2013 .

[28]  N. Yonemoto,et al.  Outcomes of very‐low‐birthweight infants at 3 years of age born in 2003–2004 in Japan , 2011, Pediatrics international : official journal of the Japan Pediatric Society.

[29]  R. Uehara,et al.  Distribution of Birth Weight for Gestational Age in Japanese Infants Delivered by Cesarean Section , 2011, Journal of epidemiology.

[30]  A. Lapillonne,et al.  Neurologic Outcomes at School Age in Very Preterm Infants Born With Severe or Mild Growth Restriction , 2011, Pediatrics.

[31]  W. Künzel,et al.  Impact of fetal growth restriction on mortality and morbidity in a very preterm birth cohort. , 2010, The Journal of pediatrics.

[32]  J. Folkman,et al.  Maternal preeclampsia predicts the development of bronchopulmonary dysplasia. , 2010, The Journal of pediatrics.

[33]  M. Hadders‐Algra,et al.  How much loss to follow-up is acceptable in long-term randomised trials and prospective studies? , 2008, Archives of Disease in Childhood.

[34]  Graeme N. Smith,et al.  Pregnancy‐induced hypertension and infant mortality: roles of birthweight centiles and gestational age , 2006, BJOG : an international journal of obstetrics and gynaecology.

[35]  M. Fujimura,et al.  Morbidity and Mortality of Infants With Very Low Birth Weight in Japan: Center Variation , 2006, Pediatrics.

[36]  D. Henderson-smart,et al.  Hypertensive disorders in pregnancy: a population‐based study , 2005, The Medical journal of Australia.

[37]  C. Greenwood,et al.  Why is there a modifying effect of gestational age on risk factors for cerebral palsy? , 2005, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[38]  K. Joseph,et al.  The effect of hypertensive disorders in pregnancy on small for gestational age and stillbirth: a population based study , 2004, BMC pregnancy and childbirth.

[39]  T. O'Shea,et al.  Antecedents of cerebral palsy in very low-birth weight infants. , 2000, Clinics in perinatology.

[40]  M. Pollack,et al.  A comparison of neonatal mortality risk prediction models in very low birth weight infants. , 2000, Pediatrics.

[41]  R. Palisano,et al.  Development and reliability of a system to classify gross motor function in children with cerebral palsy , 1997, Developmental medicine and child neurology.

[42]  L. Papile,et al.  Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. , 1978, The Journal of pediatrics.

[43]  M. J. Bell,et al.  Neonatal Necrotizing Enterocolitis: Therapeutic Decisions Based upon Clinical Staging , 1978, Annals of surgery.

[44]  M. Bax TERMINOLOGY AND CLASSIFICATION OF CEREBRAL PALSY , 1964, Developmental medicine and child neurology.

[45]  S. Kusuda,et al.  Impact of being small-for-gestational age on survival and long-term outcome of extremely premature infants born at 23–27 weeks' gestation , 2007, Journal of perinatal medicine.

[46]  Y. Ogawa Birth size standards by gestational age for Japanese neonates , 1998 .