Prediction of Neonatal Metabolic Acidosis in Women with a Singleton Term Pregnancy in Cephalic Presentation

Abstract

We sought to predict neonatal metabolic acidosis at birth using antepartum obstetric characteristics (model 1) and additional characteristics available during labor (model 2). In 5667 laboring women from a multicenter randomized trial that had a high-risk singleton pregnancy in cephalic presentation beyond 36 weeks of gestation, we predicted neonatal metabolic acidosis. Based on literature and clinical reasoning, we selected both antepartum characteristics and characteristics that became available during labor. After univariable analyses, the predictors of the multivariable models were identified by backward stepwise selection in a logistic regression analysis. Model performance was assessed by discrimination and calibration. To correct for potential overfitting, we (internally) validated the models with bootstrapping techniques. Of 5667 neonates born alive, 107 (1.9%) had metabolic acidosis. Antepartum predictors of metabolic acidosis were gestational age, nulliparity, previous cesarean delivery, and maternal diabetes. Additional intrapartum predictors were spontaneous onset of labor and meconium-stained amniotic fluid. Calibration and discrimination were acceptable for both models (c-statistic 0.64 and 0.66, respectively). In women with a high-risk singleton term pregnancy in cephalic presentation, we identified antepartum and intrapartum factors that predict neonatal metabolic acidosis at birth.

Keywords

antepartum risk factors - intrapartum risk factors - neonatal metabolic acidosis - prediction model

• References

• 1 van de Riet JE, Vandenbussche FP, Le Cessie S, Keirse MJ. Newborn assessment and long-term adverse outcome: a systematic review. Am J Obstet Gynecol 1999; 180: 1024-1029
• 2 Goodwin TM, Belai I, Hernandez P, Durand M, Paul RH. Asphyxial complications in the term newborn with severe umbilical acidemia. Am J Obstet Gynecol 1992; 167: 1506-1512
• 3 Williams KP, Singh A. The correlation of seizures in newborn infants with significant acidosis at birth with umbilical artery cord gas values. Obstet Gynecol 2002; 100: 557-560
• 4 van den Berg PP, Nelen WL, Jongsma HW , et al. Neonatal complications in newborns with an umbilical artery pH <7.00. Am J Obstet Gynecol 1996; 175: 1152-1157
• 5 Lavrijsen SW, Uiterwaal CS, Stigter RH, de Vries LS, Visser GH, Groenendaal F. Severe umbilical cord acidemia and neurological outcome in preterm and full-term neonates. Biol Neonate 2005; 88: 27-34
• 6 Moons KG, Royston P, Vergouwe Y, Grobbee DE, Altman DG. Prognosis and prognostic research: what, why, and how?. BMJ 2009; 338: b375
• 7 Westerhuis ME, Visser GH, Moons KG , et al. Cardiotocography plus ST analysis of fetal electrocardiogram compared with cardiotocography only for intrapartum monitoring: a randomized controlled trial. Obstet Gynecol 2010; 115: 1173-1180
• 8 Westerhuis ME, Visser GH, Moons KG, Zuithoff N, Mol BW, Kwee A. Cardiotocography plus ST analysis of fetal electrocardiogram compared with cardiotocography only for intrapartum monitoring: a randomized controlled trial. Obstet Gynecol 2011; 117 (2 Pt 1) 406-407
• 9 Stichting Perinatale Registratie Nederland (PRN). Reference curves. 2009. Available at: http://www.perinatreg.nl/referentiecurven . Accessed September 13
• 10 Visser GH, Eilers PH, Elferink-Stinkens PM, Merkus HM, Wit JM. New Dutch reference curves for birthweight by gestational age. Early Hum Dev 2009; 85: 737-744
• 11 Fusi L, Steer PJ, Maresh MJ, Beard RW. Maternal pyrexia associated with the use of epidural analgesia in labour. Lancet 1989; 1: 1250-1252
• 12 Viscomi CM, Manullang T. Maternal fever, neonatal sepsis evaluation, and epidural labor analgesia. Reg Anesth Pain Med 2000; 25: 549-553
• 13 Sun GW, Shook TL, Kay GL. Inappropriate use of bivariable analysis to screen risk factors for use in multivariable analysis. J Clin Epidemiol 1996; 49: 907-916
• 14 Harrell Jr FE, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996; 15: 361-387
• 15 Royston P, Moons KG, Altman DG, Vergouwe Y. Prognosis and prognostic research: developing a prognostic model. BMJ 2009; 338: b604
• 16 Altman DG, Vergouwe Y, Royston P, Moons KG. Prognosis and prognostic research: validating a prognostic model. BMJ 2009; 338: b605
• 17 van der Heijden GJ, Donders AR, Stijnen T, Moons KG. Imputation of missing values is superior to complete case analysis and the missing-indicator method in multivariable diagnostic research: a clinical example. J Clin Epidemiol 2006; 59: 1102-1109
• 18 Donders AR, van der Heijden GJ, Stijnen T, Moons KG. Review: a gentle introduction to imputation of missing values. J Clin Epidemiol 2006; 59: 1087-1091
• 19 Greenland S, Finkle WD. A critical look at methods for handling missing covariates in epidemiologic regression analyses. Am J Epidemiol 1995; 142: 1255-1264
• 20 Vergouwe Y, Royston P, Moons KG, Altman DG. Development and validation of a prediction model with missing predictor data: a practical approach. J Clin Epidemiol 2010; 63: 205-214
• 21 Rubin DB. Multiple Imputation for Non Response in Surveys. New York: Wiley; 1987
• 22 Atkinson A. A note on the generalized information criterion for choice of a model. Biometrika 2010; 67: 413-418
• 23 Miller ME, Hui SL, Tierney WM. Validation techniques for logistic regression models. Stat Med 1991; 10: 1213-1226
• 24 Steyerberg EW, Borsboom GJ, van Houwelingen HC, Eijkemans MJ, Habbema JD. Validation and updating of predictive logistic regression models: a study on sample size and shrinkage. Stat Med 2004; 23: 2567-2586
• 25 Steyerberg EW, Bleeker SE, Moll HA, Grobbee DE, Moons KG. Internal and external validation of predictive models: a simulation study of bias and precision in small samples. J Clin Epidemiol 2003; 56: 441-447
• 26 Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord pH and perinatal and long term outcomes: systematic review and meta-analysis. BMJ 2010; 340: c1471
• 27 Evers AC, Brouwers HA, Hukkelhoven CW , et al. Perinatal mortality and severe morbidity in low and high risk term pregnancies in the Netherlands: prospective cohort study. BMJ 2010; 341: c5639
• 28 Amelink-Verburg MP, Rijnders ME, Buitendijk SE. A trend analysis in referrals during pregnancy and labour in Dutch midwifery care 1988–2004. BJOG 2009; 116: 923-932
• 29 MacLennan A. A template for defining a causal relation between acute intrapartum events and cerebral palsy: international consensus statement. BMJ 1999; 319: 1054-1059
• 30 Low JA, Lindsay BG, Derrick EJ. Threshold of metabolic acidosis associated with newborn complications. Am J Obstet Gynecol 1997; 177: 1391-1394
• 31 Moons KG, Altman DG, Vergouwe Y, Royston P. Prognosis and prognostic research: application and impact of prognostic models in clinical practice. BMJ 2009; 338: b606