A poor long-term neurological prognosis is associated with abnormal cord insertion in severe growth-restricted fetuses
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Masamitsu Nakamura
,
Nagayoshi Umehara
Abstract
Objective:
To clarify and compare if the neurological outcomes of fetal growth restriction (FGR) cases with abnormal cord insertion (CI) are associated with a higher risk of a poor neurological outcome in subjects aged 3 years or less versus those with normal CI.
Methods:
A multicenter retrospective cohort study was conducted among patients with a birth weight lower than the 3rd percentile, based on the standard reference values for Japanese subjects after 22 weeks’ gestation, who were treated at a consortium of nine perinatal centers in Japan between June 2005 and March 2011. Patients whose birth weights were less than the 3rd percentile and whose neurological outcomes from birth to 3 years of age could be checked from their medical records were analyzed. The relationship between abnormal CI and neurological outcomes was analyzed. Univariate and multivariate models of multivariate logistic regression were employed to estimate the raw and odds ratio (OR) with 95% confidence intervals comparing marginal (MCI) and velamentous cord insertion (VCI) to normal CI.
Results:
Among 365 neonates, 63 cases of MCI and 14 cases of VCI were observed. After excluding 24 cases with neonatal or infant death from the total FGR population, the assessment of the outcomes of the infants aged 3 years or younger showed the following rates of neurological complications: 7.3% (n=25) for cerebral palsy, 8.8% (n=30) for developmental disorders, 16.7% (n=57) for small-for-gestational-age short stature (SGA), 0.6% (n=2) for impaired hearing, 0.9% (n=3) for epilepsy, 1.2% (n=4). The ORs (95% confidence intervals) based on multivariate analysis were as follows: cerebral palsy=10.1 (2.4–41.5) in the VCI group and 4.3 (1.6–11.9) in the MCI group, developmental disorders=6.7 (1.7–26) in the VCI group and 3.9 (1.1–14.2) in the single umbilical artery (SUA) group, 5.1 (1.4–18.7) for birth weight <1000 g and 2.8 (1.2–6.7) for placental weight <200 g.
Conclusions:
The present results indicate that growth-restricted fetuses diagnosed with a birth weight below the 3rd percentile exhibiting abnormal umbilical CI are at a high risk for poor neurological outcomes, including cerebral palsy and/or developmental disorders.
Acknowledgments:
We appreciate the contributions to this study made by Nagayoshi Umehara and Haruhiko Sago at Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Keisuke Ishii and Jun Sasahara at Osaka Medical Center and Research Institute for Maternal and Child Health, Kenji Kiyoshi at Hyogo Children’s Hospital, Katsusuke Ozawa at Miyagi Children’s Hospital, Kei Tanaka at Kyorin University Hospital, Tomohiro Tanemoto at Jikei University Hospital, Junichi Hasegawa at St. Marianna University Hospital School of Medicine, Kiyotake Ichizuka at Showa University School of Medicine, Hiroshi Ishikawa at Kanagawa Children’s Medical Center and Takeshi Murakoshi at Seirei Hamamatsu General Hospital.
Author’s statement
Conflict of interest: Authors state no conflict of interest. No funding sources supported this study. This study was approved by the Ethics Committee of all the institutions.
Material and methods: Informed consent: Informed consent has been obtained from all individuals included in this study.
Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.
References
[1] Misra DP, Salafia CM, Miller RK, Charles AK. Non-linear and gender-specific relationships among placental growth measures and the fetoplacental weight ratio. Placenta. 2009;30:1052–7.10.1016/j.placenta.2009.09.008Search in Google Scholar
[2] Ebbing C, Kiserud T, Johnsen SL, Albrechtsen S, Rasmussen S. Prevalence, risk factors and outcomes of velamentous and marginal cord insertions: a population-based study of 634,741 pregnancies. PLoS One. 2013;8:e70380.10.1371/journal.pone.0070380Search in Google Scholar
[3] Hasegawa J, Matsuoka R, Ichizuka K, Sekizawa A, Farina A, Okai T. Velamentous cord insertion into the lower third of the uterus is associated with intrapartum fetal heart rate abnormalities. Ultrasound Obstet Gynecol. 2006;27:425–9.10.1002/uog.2645Search in Google Scholar
[4] Hasegawa J, Matsuoka R, Ichizuka K, Sekizawa A, Okai T. Velamentous cord insertion: significance of prenatal detection to predict perinatal complications. Taiwan J Obstet Gynecol. 2006;45:21–5.10.1016/S1028-4559(09)60185-6Search in Google Scholar
[5] Hasegawa J, Matsuoka R, Ichizuka K, Sekizawa A, Farina A, Okai T. Velamentous cord insertion and atypical variable decelerations with no accelerations. Int J Gynaecol Obstet. 2005;90:26–30.10.1016/j.ijgo.2005.03.028Search in Google Scholar
[6] Hasegawa J, Matsuoka R, Ichizuka K, Kotani M, Nakamura M, Mikoshiba T, et al. Atypical variable deceleration in the first stage of labor is a characteristic fetal heart-rate pattern for velamentous cord insertion and hypercoiled cord. J Obstet Gynaecol Res. 2009;35:35–9.10.1111/j.1447-0756.2008.00863.xSearch in Google Scholar
[7] Redline RW. Clinical and pathological umbilical cord abnormalities in fetal thrombotic vasculopathy. Hum Pathol. 2004;35:1494–8.10.1016/j.humpath.2004.08.003Search in Google Scholar
[8] Kraus FT, AcheenVI. Fetal thrombotic vasculopathy in the placenta: cerebral thrombi and infarcts, coagulopathies, and cerebral palsy. Hum Pathol. 1999;30:759–69.10.1016/S0046-8177(99)90136-3Search in Google Scholar
[9] Eddleman KA, Lockwood CJ, Berkowitz GS, Lapinski RH, Berkowitz RL. Clinical significance and sonographic diagnosis of velamentous umbilical cord insertion. Am J Perinatol. 1992;9:123–6.10.1055/s-2007-994684Search in Google Scholar PubMed
[10] Yoshida A, Umehara N, Sasahara J, Ozawa K, Ichizuka K, Tanaka K, et al. Prenatal risk stratification of severe small-for-gestational-age infants: a Japanese multicenter study. J Matern Fetal Neonatal Med. 2016;29:1353–7.10.3109/14767058.2015.1049147Search in Google Scholar PubMed
[11] Itabashi K, Miura F, Uehara R, Nakamura Y. New Japanese neonatal anthropometric charts for gestational age at birth. Pediatr Int. 2014;56:702–8.10.1111/ped.12331Search in Google Scholar
[12] Visentin S, Macchi V, Grumolato F, Porzionato A, De Caro R, Cosmi E. Expectant management in type II selective intrauterine growth restriction and abnormal cord insertion in monochorionic twins. J Perinat Med. 2013;41:309–16.10.1515/jpm-2012-0133Search in Google Scholar
[13] Higgins JR, de Swiet M. Blood-pressure measurement and classification in pregnancy. Lancet. 2001;357:131–5.10.1016/S0140-6736(00)03552-2Search in Google Scholar
[14] Bastide A, Manning F, Harman C, Lange I, Morrison I. Ultrasound evaluation of amniotic fluid: outcome of pregnancies with severe oligohydramnios. Am J Obstet Gynecol. 1986;154:895–900.10.1016/0002-9378(86)90479-5Search in Google Scholar
[15] Bax MC. Terminology and classification of cerebral palsy. Dev Med Child Neurol. 1964;6:295–7.10.1111/j.1469-8749.1964.tb10791.xSearch in Google Scholar
[16] Society for the Kyoto Scale of Psychological Development Test. Kyodaishiki developmental schedule New edition 2001. [T.K.S.o.P.D.T. 2001]. Nakanishiya Shuppan: Kyoto, 2008. (in Japanese)Search in Google Scholar
[17] Leistra-Leistra MJ, Timmer A, van Spronsen FJ, Geven WB, van der Meer J, Erwich JJ. Fetal thrombotic vasculopathy in the placenta: a thrombophilic connection between pregnancy complications and neonatal thrombosis? Placenta. 2004; 25(Suppl A):S102–5.10.1016/j.placenta.2004.01.010Search in Google Scholar
[18] Dahms BB, Boyd T, Redline RW. Severe perinatal liver disease associated with fetal thrombotic vasculopathy. Pediatr Dev Pathol. 2002;5:80–5.10.1007/s10024-001-0111-5Search in Google Scholar
[19] Benirschke K. Obstetrically important lesions of the umbilical cord. J Reprod Med. 1994;39:262–72.Search in Google Scholar
[20] Tantbirojn P, Saleemuddin A, Sirois K, Crum CP, Boyd TK, Tworoger S, et al. Gross abnormalities of the umbilical cord: related placental histology and clinical significance. Placenta. 2009;30:1083–8.10.1016/j.placenta.2009.09.005Search in Google Scholar
[21] Nelson KB, Ellenberg JH. Apgar scores as predictors of chronic neurologic disability. Pediatrics. 1981;68:36–44.10.1542/peds.68.1.36Search in Google Scholar
[22] Odd DE, Lewis G, Whitelaw A, Gunnell D. Resuscitation at birth and cognition at 8 years of age: a cohort study. Lancet. 2009;373:1615–22.10.1016/S0140-6736(09)60244-0Search in Google Scholar
[23] McCormick MC, Brooks-Gunn J, Buka SL, Goldman J, Yu J, Salganik M, et al. Early intervention in low birth weight premature infants: results at 18 years of age for the Infant Health and Development Program. Pediatrics. 2006;117: 771–80.10.1542/peds.2005-1316Search in Google Scholar PubMed
[24] Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. Br Med J. 2010;340:c363.10.1136/bmj.c363Search in Google Scholar PubMed PubMed Central
[25] Spittle AJ, Orton J, Doyle LW, Boyd R. Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants. Cochrane Database Syst Rev. 2007:CD005495.10.1002/14651858.CD005495.pub2Search in Google Scholar PubMed
[26] Paneth N, Stark RI. Cerebral palsy and mental retardation in relation to indicators of perinatal asphyxia. An epidemiologic overview. Am J Obstet Gynecol. 1983;147:960–6.10.1097/00132582-198406000-00002Search in Google Scholar
[27] Sepúlveda WH. Antenatal sonographic detection of single umbilical artery. J Perinat Med. 1991;19:391–5.10.1515/jpme.1991.19.5.391Search in Google Scholar PubMed
©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Fetal anomalies – From prenatal diagnosis to therapy
- Corner of Academy
- The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications
- Research articles – Obstetrics
- Assessment of strain and dyssynchrony in normal fetuses using speckle tracking echocardiography – comparison of three different ultrasound probes
- Inborn errors of metabolism in a cohort of pregnancies with non-immune hydrops fetalis: a single center experience
- Cytogenetic analysis in fetuses with late onset abnormal sonographic findings
- Fetal MRI, lower acceptance by women in research vs. clinical setting
- Neurological complications after therapy for fetal-fetal transfusion syndrome: a systematic review of the outcomes at 24 months
- Evaluation of management and surgical outcomes in pregnancies complicated by acute cholecystitis
- Pentaerythrityltetranitrate (PETN) improves utero- and feto-placental Doppler parameters in pregnancies with impaired utero-placental perfusion in mid-gestation – a secondary analysis of the PETN-pilot trial
- Early onset preeclampsia is associated with an elevated mean platelet volume (MPV) and a greater rise in MPV from time of booking compared with pregnant controls: results of the CAPE study
- Effect of maternal age, height, BMI and ethnicity on birth weight: an Italian multicenter study
- Risk factors and classification of stillbirth in a Middle Eastern population: a retrospective study
- Selective IUGR in dichorionic twins: what can Doppler assessment and growth discordancy say about neonatal outcomes?
- Early fetal megacystis: Is it possible to predict the prognosis in the first trimester?
- Research articles – Fetus
- A poor long-term neurological prognosis is associated with abnormal cord insertion in severe growth-restricted fetuses
- Birth-weight centiles and the risk of serious adverse neonatal outcomes at term
- Short communication
- Maternal and neonatal vitamin D deficiency and transient tachypnea of the newborn in full term neonates
- Acknowledgment
Articles in the same Issue
- Frontmatter
- Editorial
- Fetal anomalies – From prenatal diagnosis to therapy
- Corner of Academy
- The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications
- Research articles – Obstetrics
- Assessment of strain and dyssynchrony in normal fetuses using speckle tracking echocardiography – comparison of three different ultrasound probes
- Inborn errors of metabolism in a cohort of pregnancies with non-immune hydrops fetalis: a single center experience
- Cytogenetic analysis in fetuses with late onset abnormal sonographic findings
- Fetal MRI, lower acceptance by women in research vs. clinical setting
- Neurological complications after therapy for fetal-fetal transfusion syndrome: a systematic review of the outcomes at 24 months
- Evaluation of management and surgical outcomes in pregnancies complicated by acute cholecystitis
- Pentaerythrityltetranitrate (PETN) improves utero- and feto-placental Doppler parameters in pregnancies with impaired utero-placental perfusion in mid-gestation – a secondary analysis of the PETN-pilot trial
- Early onset preeclampsia is associated with an elevated mean platelet volume (MPV) and a greater rise in MPV from time of booking compared with pregnant controls: results of the CAPE study
- Effect of maternal age, height, BMI and ethnicity on birth weight: an Italian multicenter study
- Risk factors and classification of stillbirth in a Middle Eastern population: a retrospective study
- Selective IUGR in dichorionic twins: what can Doppler assessment and growth discordancy say about neonatal outcomes?
- Early fetal megacystis: Is it possible to predict the prognosis in the first trimester?
- Research articles – Fetus
- A poor long-term neurological prognosis is associated with abnormal cord insertion in severe growth-restricted fetuses
- Birth-weight centiles and the risk of serious adverse neonatal outcomes at term
- Short communication
- Maternal and neonatal vitamin D deficiency and transient tachypnea of the newborn in full term neonates
- Acknowledgment
