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    Should women with intrahepatic cholestasis of pregnancy be delivered early?

     

    However, one recent study did consider comorbidities in ICP-affected pregnancies.21 This was a review of a retrospective multisite cohort of 233 symptomatic women with total bile acids (TBA) levels that ranged from 0 μmol/L to > 100 μmol/L. While the authors found the prevalence of maternal comorbid stillbirth risk factors was not affected by the severity of the disease, it is notable that all 4 stillbirths in the cohort occurred in pregnancies most severely affected by ICP as designated by TBA levels > 100 μmol/L. Although the findings in this study are certainly suggestive of an association between elevated TBA and fetal demise, as in many previous reviews of large data sets, critical relevant obstetric information is missing. In particular, no data are provided concerning gestational age or existence of comorbid conditions complicating the pregnancies that ended in stillbirth. No information is provided about the use of active management of ICP-affected pregnancies during the 2009 to 2014 study period.

    Lack of benefit to active management

    Active management of ICP has its foundation in reports published between 1964 and 2014 that consisted of only 20 unexplained term stillbirths including 6 pregnancies affected by cardiovascular comorbidities.22-24 A review of the published literature finds no evidence to reject the null hypothesis that there is no difference in stillbirth rates for pregnancies affected and unaffected by ICP.8

    In contrast, there is robust evidence that when compared to full-term (FT) infants (39 to 42 weeks’ gestation), ET (37 to 39 weeks’ gestation) and LPT infants (incorrectly dated 34–35 and 36 weeks’ gestation) are at increased risk for short-term respiratory morbidity, admission to neonatal intensive care units, and for the first 8 to 9 years of life, lower lung function as measured by a spirometer.25,26 When compared to FT infants, ET infants are at increased risk for lower cognitive ability; importantly, this is a finding that persists into adulthood.27,28 Several reports indicate that LPT and ET infants are at increased risk for needing special education, achieving less education, and having poorer cognitive abilities than FT infants.29-31 After controlling for socioeconomic confounders, investigators found persistent differences in neurocognitive abilities among LPT and ET children as manifested by generally performing less well on cognitive and language tests than their FT-born counterparts.32 This altered neurocognitive function seems to continue into adulthood as measured by poorer episodic memory performance.33

    Next: What to say and do right when things go terribly wrong in obstetrics

    Whereas there is no evidence to support ICP as an independent risk factor for unexplained term stillbirth, robust data exist that when compared to FT infants born before 39 weeks’ gestation, LPT infants delivered at 34 to 36 weeks and ET infants delivered at 37 to 38 weeks are at increased risk for short- and long-term adverse outcomes.34

    References

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    2. Lee RH, Goodwin TM, Greenspoon J, Incerpi M. The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population. J Perinatol 2006;26:527-532

    3. Roszkowski I, Pisarek-Miedzinska D. Jaundice in pregnancy. II. Clinical course of pre-pregnancy and delivery and condition of neonate. Am J Obstet Gynecol .1968;101:500-503.

    4. MacDorman MF, Kirmeyer SE, Wilson EC. Fetal and perinatal morality, United States, 2013. National Vital Statistics Report Vol 64, no 8, Hyattsville, MD: National Center for Health Statistics, 2015

    5. DelkeI, Hyatt R, Feinkind L, Minkoff H. Avoidable causes of perinatal death at or after term pregnancy in an inner-city hospital: Medical versus social. Am J Obstet Gynecol. 1988;159:562-566

    6. Reddy UM, Laughon SK, Sun L, Troendle J, Willinger M, Zhang J. Prepregnancy risks factors for antepartum stillbirth in the United States. Obstet Gynecol. 2010:116:1119-1126

    7. Gray R, Quigley M, Hockley G, Kurinczuk J, Goldarce M, Brocklehurst P. Caesarean delivery and risk of stillbirth in subsequent pregnancy: a retrospective cohort study in an English population. BJOG; 2007:114:264-270

    8. Bahtiyar MO, Julien S, Robinson JN, et al. Prior cesarean delivery is not associated with an increased risk of stillbirth in a subsequent pregnancy: analysis of U.S. perinatal mortality data, 1995-1997. Am J Obstet Gynecol. 2006;195(5):1373

    9. Qui Zhong-da, Wang Qi-nan, Liu Yue-han, Maio He-Zhang. Intrahepatic Cholestasis of Pregnancy Clinical analysis and follow-up of 22 Cases . Chinese Medical Journal 1983 96(12):902-906

    10. Reid R, Ivey KJ, Rencoret, Storey B. Fetal Complications of obstetric cholestasis. Br Med K 1976;1:870-872

    11. Henderson, C.E., Shah, R.R., Gottimukkala, S., Ferreira, K.K., Hamaoui, A., Mercado, R. Primum non nocere: how active management became modus operandi for intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol. 2014:211:189–196

    12. Rioseco AJ. Ivankovec MD, Manzur A, Hamed F, Kato SR, Parer JT, Germain AM. Intrahepatic cholestasis of pregnancy: A retrospective case-control study of perinatal outcome. Am J Obstet Gynecol. 1994;170:890-895

    13. Spong CY, Mercer BM, D’Alton M, Kilpatrick S, Blackwell S, Saade G. Timing of indicated late-preterm and early-term birth. Obstet Gynecol 2011;118:323–333.

    14. Gouyon JB, Vintejoux A, Sagot P, Burguet A, Quantin C, Ferdynus C, Burgundy Perinatal Network. Neonatal outcome associated with singleton birth at 34-41 weeks of gestation. International journal of epidemiology. 2010;39:769-776

    15. Dudley DH, Goldenberg R, Conway D, et al. A new system for determining the causes of stillbirth. Obstet Gynecol. 2010;116:254-260

    16. Flenady V, Koopmans L, Middleton P, et al. Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis. Lancet. 2011;377:1331-1340

    17. Gardosi J, Madurasinghe V, Williams M, Mailk A, Francis A. Maternal and fetal risk factors for stillbirth. BMJ 2013;346:f108

    18. Fretts RG. Etiology and prevention of stillbirth. Am J Obstet Gynecol 2005; 193, 1923-1935

    19. Geens V, Chappell LC, Sneed PT, Steer PJ, Knight M, Williamson C. Association of Severe Intrahepatic Cholestasis of Pregnancy with Adverse Pregnancy Outcomes: A Prospective Population-Based Case-Control Study. Hepatology 2014;49:1482-1491

    20. Puljic A, Kim E, Page J, et al. The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age. Am J Obstet Gynecol .2015;212:667.e1-5

    21. Kawakita T, Parikh LI, Ramsey PS, et al. Predictors of adverse neonatal outcomes in intrahepatic cholestasis of pregnancy. Am J Obstet Gyneol 2015;214:570.e1-8

    22. Alsulyman OM, Ouzounian JG, Ames-Castrol M, Goodwin TM. Intrahepatic Cholestasis of pregnancy: perinatal outcome associated with expectant management. Am J Obstetric Gynecol. 1996:175;957-960

    23. Berg B, Helm G, Petersohn L, Tryding. Cholestasis of Pregnancy. Acta Obstet Gynecol Scand 1986 65:107-113

    24. Laatikainen T, Ikonen E. Fetal Prognosis in Obstetric Hepatoisis. Ann Chir Gynaecol Fenn 1975;64(3):155-164

    25. Kitcha SJ, Watkins WJ, Lowe J, Henderson AJ, Katecha S. Effect of early-term birth on respiratory symptomssyptoms and lung function in childhood and adolescence. Pediatri Pulmonol 2016; doi: 10.1002/ppul;/23448

    26. Harju M, Keski-Nisula L, Georgiadis L, Räisänen S, Gissler M, Heinonen S. 20143 The burden of childhood asthma and late preterm and early term births. J Pediatr 2014;164(2):295-299.

    27. Poulsen, G, Wolke D, Kurinczuk JJ, et al. Gestational age and cognitive ability in early childhood: a population-based cohort study. Paediatirc and Perinatal Epidemiology 2013;27,371-379

    28. Sengupta S, Carrion V, Shelton J, et al. JAMA Pediatr 2013:167(1):1053-1059

    29. Moster D, Lie RT. Moster D, Markestad T. Long-term medical and social consequences of preterm birth NEJM 2008;359:262-273

    30. Mathiasen R, Hansen BM, Nybo Anderson AM, Forman JL, Greisen G. Gestational Age and Basic School Achievements: a National Follow up Study in Denmark. Pediatirics 2010;126(6)e1553-e1561

    31. Quigley MA, Polusen G, Boyle E, et al. Early term and late preterm birth are associated with poor school performance at 5 years: a cohort study. Arch Dis Child Fetal Neonatal Ed. 2012;97:F167-F173

    32. Chan E, Leong P, Malouf R, Quigley. Long-term cognitive and school outcomes for late-preterm and early-term births: a systematic review. Child: care, health and development. 2015: 42;297-312.

    33. Heinon K, Eriksson JG, Lahti J, et al. Late Preterm Birth and Neurocognitive Performance in Late Adulthood: A Birth Cohort Study. Pediatrics. 2015;135:(4)e2014-3556

    34. Hibbard JU, Wilkins I, Sun L, et al. Consortium on Safe Labor. Respiratory morbidity in late preterm births. JAMA. 2010;304:419-415.

    35. Kapellou O, Counsell SJ, Kennea N, et al. Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth. PLoS Medicine. 2006;3(8):1382-1390.

    36. Morzurkewich E, Chilimigras J, Koepke E, Keeton K, King VJ. Indications for induction of labor: a best-evidence review. BJOG. 2009; 626-636.

    Cassandra E Henderson, MD, CDE
    Dr Henderson is Director of Maternal Fetal Medicine at Lincoln Medical and Mental Health Center and Professor of Clinical Obstetrics and ...

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