Perinatal Morbidity and Mortality in Late-Term and Post-Term Pregnancy

Home , Birth injury, Chorioamnionitis, Postterm pregnancy, Stillbirth

Journal of Perinatology (2011) 31, 789–793 r 2011 Nature America, Inc. All rights reserved. 0743-8346/11 www.nature.com/jp ORIGINAL ARTICLE Perinatal morbidity and mortality in late-term and post-term pregnancy. NEOSANO perinatal network’s experience in Mexico

AM De los Santos-Garate1, M Villa-Guillen1, D Villanueva-Garc´ıa1, ML Vallejos-Ru´ız1 and MT Murgu´ıa-Peniche2 and the NEOSANO’s Network 1Department of Neonatology, Hospital Infantil de Mexico Federico Gomez, Me´xico City, Me´xico and 2National Center for Child and Adolescent Health (CeNSIA), Me´xico City, Me´xico

Keywords: perinatal outcomes; pregnancy X40 weeks; Mexican Objective: The objective of this study is to identify adverse perinatal population outcomes associated with pregnancies at or beyond 40 weeks.

Study Design: Retrospective cohort study conducted in Mexico, with information obtained from the NEOSANO’s Perinatal Network Database Post-term pregnancy is defined as gestation that extends beyond from April 2006 to April 2009. Multiple births, babies with inaccurate 42 weeks.1 The relative perinatal mortality is higher in post-term gestational age or babies with congenital malformations were excluded. delivery compared with delivery at term and has been associated Logistic regression models were used to analyze perinatal complications with an increased frequency of neonatal morbidity (meconium associated with pregnancies X40 weeks. aspiration, fetal distress, asphyxia in the neonatal period, Result: A total of 21 275 babies were analyzed; of these, 4545 (21.3%) were pneumonia, malformations, macrosomia and fetal birth injury) 6 6 of 40 to 407 weeks, 3024 (14.2%) 41 to 417 weeks and 388 (1.8%) 42 to 44 and maternal complications (cesarean section, postpartum 6 2 weeks of gestation. Adverse perinatal outcomes associated with 40 to 407 hemorrhage, labor dysfunction and obstetric trauma). Although it weeks deliveries were (odds ratio; 95% confidence interval): macrosomia is known that these risks are increased in post-term pregnancies, (1.9; 1.5 to 2.6), acute fetal distress (1.4; 1.2 to 1.7), emergency cesarean what has received less attention is whether and to what extent these delivery (1.4; 1.2 to 1.5) and chorioamnionitis (1.4; 1.2 to 1.6). Adverse risks increase before 42 weeks of gestation. Currently, the American 6 perinatal outcomes associated with 41 to 417 weeks were macrosomia (2.5; College of Obstetricians and Gynecologists (ACOG) recommends 1.8 to 3.3), chorioamnionitis (2; 1.7 to 2.3), emergency cesarean delivery initiation of antenatal surveillance between 41 and 42 weeks of (1.8; 1.6 to 2.1) and acute fetal distress (1.4; 1.1 to 1.7). Adverse perinatal gestation.3 However, some studies have demonstrated an increased outcomes associated with 42 to 44 weeks were macrosomia (7; 4.6 to 10.7), risk of perinatal complications with deliveries as early as 40 weeks. meconium aspiration syndrome (5.6; 2.8 to 11.2), neonatal death (4.8; 1.7 Caughey et al.4,5 reported that at a community hospital, maternal to 13.8), stillbirth (4.3; 1.4 to 13.5), 50 Apgar <4 (4.2; 1.1 to 15.7), and neonatal complications were observed at 40 to 42 weeks of chorioamnionitis (2.8; 2.2 to 3.9), admission to neonatal intensive care unit gestation, suggesting a need for additional study of this cohort. (2.7; 1.5 to 4.8), admission to neonatal intensive care unit or step-down unit In Mexico, there is scant information regarding the incidence (2.4; 1.5 to 3.9), acute fetal distress (1.8; 1.2 to 2.6) and emergency cesarean of and perinatal outcomes associated with pregnancies at or delivery (1.8; 1.3 to 2.4). beyond 40 weeks’ gestation. The aim of this study was to identify Conclusion: An increased risk for perinatal and maternal complications perinatal morbidity and mortality associated with late-term were detected as early as 40 weeks’ gestation. The risks of stillbirth and and post-term pregnancy, as compared with term pregnancies 6 neonatal death were significantly higher in the post-term group than the (39 to 397 weeks’ gestation). control group. Journal of Perinatology (2011) 31, 789–793; doi:10.1038/jp.2011.43; published online 16 June 2011 Methods Population Correspondence: Dr MT Murguıá-Peniche, Area Director-Infancy, National Center for Child All babies (live birth or dead X400 g) born from April 2006 and Adolescent Health (CeNSIA), Francisco de P. Miranda 177, 1 er piso, Col. Merced Go´mez, to April 2009 at the study hospitals in NEOSANO’s Perinatal 01600 Deleg. A. Obregoń, Me´xico, D.F., Me´xico. Network in Mexico (five hospitals at Mexico City, three hospitals E-mail: [email protected] Received 9 March 2010; revised 6 March 2011; accepted 15 March 2011; published online at Tlaxcala City and one hospital at Oaxaca City) were included. 16 June 2011 This network gathers social, gynecological, obstetric, baseline Perinatal complications in late-term and post-term pregnancies AM De los Santos-Garate et al 790 maternal medical conditions and neonatal data. Multiple births, this figure was significantly higher (40%) for those mothers who babies with congenital malformations or inaccurate gestational delivered at or beyond at 40 weeks’ gestation. The frequency of poor age were excluded. prenatal care, defined as less than four prenatal visits, was more prevalent among those pregnancies that lasted >40 weeks. The Gestational age assessment most common obstetric complications were chorioamnionitis Gestational age was calculated by dates (when known) or and prolonged rupture of membranes. Of note, 38 to 55% of the 6 7 alternatively by Ballard Score, Capurro Score or prenatal cases were delivered by emergency cesarean section. ultrasound. Table 2 summarizes the frequency of adverse perinatal outcomes by gestational age. In general, obstetric complications Design increased as gestational age advanced beyond 39 to 40 weeks. For each delivery, a trained field worker completed a questionnaire, Preeclampsia and chorioamnionitis was approximately twice as which included pertinent social, gynecological, obstetric, perinatal common in the 42 to 44-week gestational group as compared and baseline maternal medical data. All babies were followed up with the 39 weeks group. until discharge. As expected, the greater the gestational age beyond 39 weeks, We examined the following outcomes: maternal vaginal the higher the frequency of adverse neonatal outcomes, and these bleeding, chorioamnionitis, emergency cesarean delivery, elective were mainly associated with acute fetal distress, macrosomia cesarean delivery, 5 min Apgar score less than 4, acute fetal distress, and death. macrosomia, meconium aspiration syndrome, admission to The association between gestational age and adverse perinatal the neonatal intensive care or step-down unit, stillbirth and outcomes (adjusted analysis) is presented in Table 3. A significant neonatal death. increased risk of perinatal morbidity (chorioamnionitis, emergency cesarean delivery, acute fetal distress and macrosomia) was Statistical Analysis observed as early as 40 weeks compared with 39 weeks’ gestation. The population was divided into three groups: post-term (42 to 44 The same outcomes were also associated with pregnancies at weeks’ gestation), a late-term group of 40 to 406 weeks, and a 7 42 to 44 weeks, but the odds ratios were higher. Post-term second late-term group of 41 to 416 weeks’ gestation. Pregnancies 7 pregnancies also demonstrated additional complications such as at 39 to 396 weeks’ gestation were used for the control group. Risks 7 5 min Apgar score less than 4, meconium aspiration syndrome, (odds ratio; 95% confidence interval) for selected perinatal admission to the neonatal intensive care or step-down unit, outcomes were assessed by several logistic regression models stillbirth and neonatal death. controlled for cofounders: maternal age, <6 years of education, marital status, smoking during pregnancy, history of adverse perinatal outcomes (such as previous preterm birth, stillbirth Discussion and congenital malformations), maternal chronic diseases In this study, the frequency of pregnancies beyond 396 weeks (diabetes mellitus, thyroid disease), nulliparity, gestational 7 was approximately 37%. This represents an important proportion diabetes, preeclampsia, eclampsia, prenatal care and gender. of all deliveries and as such, it is important to analyze adverse SPSS 16.0 for Windows was used for analysis. perinatal outcomes in this population in order to obtain an increased understanding of the problem to be able to improve outcomes. Results Previous reports noted that the best outcomes occurred when the 6 8 There were 23 231 births in the study period; 1956 (8.4%) were length of pregnancy ranges from 37 to 417 weeks of gestation. It is excluded: 1295 (6%) multiple births, 419 (1.8%) for inaccurate widely accepted that infants born before or after this period, have gestational age and 242 (1%) for congenital malformations. The more perinatal complications. However, although controversial, gestational age was calculated by Capurro Score n ¼ 13 703 (64%), there are some studies that have found increased perinatal risk dates n ¼ 7448 (35%), prenatal ultrasound n ¼ 106 (0.5%) and as early as 40 weeks’ gestation.3,9 the New Ballard Score 18 (0.1%). A total of 21 275 infants were In this study population, the rate of adolescent women among 6 analyzed; of these, 4545 (21.3%) were 40 to 407 weeks’ gestation, pregnancies >39 weeks was higher than those of shorter duration 6 3024 (14.2%) 41 to 417 weeks’ gestation and 388 (1.8%) 42 to and the rates were also high in relation to that reported in our 44 weeks’ gestation. country, which is estimated to be 17% of all pregnancies. It would The maternal characteristics of the study population are shown be interesting to see if adolescence is related to prolonged in Table 1. There were a large number of adolescents among pregnancy, possibly as a result of immaturity of the endocrine pregnancies with prolonged gestations. Approximately, one third of system or some other reason. Also, it was interesting to note that the study population had body mass index >25 kg mÀ2. However, the frequency of overweight and or obesity was higher as the length

Journal of Perinatology Perinatal complications in late-term and post-term pregnancies AM De los Santos-Garate et al 791

Table 1 Maternal characteristics by gestational age groups

39 weeks n ¼ 5034 40 weeks n ¼ 4545 41 weeks n ¼ 3024 42–44 weeks n ¼ 388 Total births n ¼ 21 275 n (%) n (%) n (%) n (%) n (%)

Demographic Age <20 years 795 (15.7) 923 (20.3)* 753 (24.9)** 76 (19.5)*** 3356 (15.7) X35 years 696 (13.8) 455 (10)** 220 (7.2)** 35 (9)w 3152 (14.8) Education <6 years 263 (5.2) 277 (6) 227 (7.5)** 39 (10)** 1054 (4.9) Marital status Single 664 (13.1) 727 (15.9)w 637 (21)** 65 (16.7)*** 2829 (13.2) Smoking during pregnancy 50 (1) 46 (1) 63 (2.1)** 3 (0.7) 2372 (11.1) Body mass index >25 kg mÀ2a 868 (30.2) 916 (36.3)** 740 (40.6)** 56 (40.6)w 4453 (34.12)

Chronic maternal diseases Diabetes mellitus 26 (0.5) 19 (0.4) 8 (0.2) 1 (0.2) 105 (0.5) Thyroid disease 60 (1.1) 33 (0.7)*** 20 (0.6)*** 1 (0.2) 301 (1.4)

Gyneco-obstetric Nulliparity 2159 (42) 1917 (42) 1220 (40)*** 162 (41) 8714 (40) <4 prenatal visits 485 (9.6) 545 (11.9)* 404 (13.3)** 51 (13.1)*** 2099 (9.8) Prolonged rupture of 605 (12) 330 (7.2)** 134 (4.4)** 14 (3.6)** 2827 (13.2) membranes >18h an ¼ 2878, 2521, 1824, 138 and 13 072 for 39, 40, 41, 42–44 weeks and total births, respectively. *P<0.001, **P<0.00001, ***P<0.05, wP<0.0001. w2-analysis was run for comparison.

Table 2 Frequency of adverse perinatal outcomes by gestational age groups

39 weeks n ¼ 5034 40 weeks n ¼ 4545 41 weeks n ¼ 3024 42–44 weeks n ¼ 388 Total births n ¼ 21 275 n (%) n (%) n (%) n (%) n (%)

Maternal outcomes Eclampsia 4 (0.1) 4 (0.1) 2 (0.1) 1 (0.2) 37 (0.1) Preeclampsia 212 (4.2) 176 (3.2) 133 (4.4) 28 (7.2)* 1069 (5) Gestational diabetes 51 (1) 25 (0.5)* 24 (0.8) 0 205 (1) Chorioamnionitis 363 (7.2) 444 (9.7)** 423 (13.9)** 73 (18.8)** 1920 (9) Painful transvaginal bleeding 143 (2.8) 91 (2)* 93 (3) 7 (1.8) 633 (2.9) Emergency cesarean section 984 (19.5) 961 (21.1) 794 (26.2)** 108 (27.8)** 4821 (22.6) Elective cesarean section 1594 (31.6) 1087 (23.9)** 614 (20.3)** 87 (22.4)*** 7134 (33.5)

Neonatal outcomes Acute fetal distress 221 (4.3) 288 (6.3)** 191 (6.3)w 30 (7.7)* 1061 (5) 50 Apgar<4 9 (0.1) 7 (0.1) 8 (0.2) 3 (0.7) 193 (0.9) Macrosomia 73 (1.4) 126 (2.7)** 103 (3.4)** 35 (9)** 377 (1.7) MAS 26 (0.5) 26 (0.5) 26 (0.8) 12 (3)** 118 (0.5) NICU admission 76 (1.5) 51 (1.1) 34 (1.1) 14 (3.6)w 726 (3.4) NICU/step-down unit admission 103 (2) 75 (1.6) 65 (2.1) 20 (5.1)** 1106 (5.1) Stillbirth 12 (0.2) 12 (0.2) 9 (0.3) 4 (1)ww 251 (1.1)

Neonatal death 6 (0.1) 6 (0.1) 5 (0.1) 5 (1.2)** 191 (0.9)

Abbreviations: MAS, meconium aspiration syndrome; NICU, neonatal intensive care unit. *P<0.01, **P<0.00001, ***P<0.0001, wP<0.001, wwP<0.05 versus 39 weeks’ gestation pregnancies. w2-analysis was run for comparison.

Journal of Perinatology Perinatal complications in late-term and post-term pregnancies AM De los Santos-Garate et al 792

Table 3 Risks of adverse perinatal outcomes associated with pregnancies at 40, 41, 42–44 weeks of gestation. Adjusted analysis

40 weeks n ¼ 4545 OR (95% CI) 41 weeks n ¼ 3024 OR (95% CI) 42–44 weeks n ¼ 388 OR (95% CI)

Chorioamnionitis 1.4 (1.2–1.6)* 2 (1.7–2.3)* 2.8 (2.2–3.9)* Painful maternal bleeding 0.7 (0.6–0.9) 1 (0.8–1.3) 0.7 (0.3–1.4) Elective cesarean section 0.7 (0.7–0.8) 0.6 (0.6–0.7) 0.7 (0.6–0.9) Emergency cesarean section 1.4 (1.2–1.5)* 1.8 (1.6–2.1)* 1.8 (1.3–2.4)* Acute fetal distress 1.4 (1.2–1.7)* 1.4 (1.1–1.7)* 1.8 (1.2–2.6)* 50 Apgar <4 1 (0.4–2.5) 1.3 (0.5–3.5) 4.2 (1.1–15.7)* Macrosomia 1.9 (1.5–2.6)* 2.5 (1.8–3.3)* 7 (4.6–10.7)* MAS 1 (0.6–1.8) 1.6 (0.9–2.7) 5.6 (2.8–11.2)* NICU admission 0.7 (0.49–1.1) 0.8 (0.5–1.2) 2.7 (1.5–4.8)* NICU/step-down unit admission 0.8 (0.56–1) 1 (0.7–1.3) 2.4 (1.5–3.9)* Stillbirth 1.1 (0.5–2.4) 1.1 (0.5–2.7) 4.3 (1.4–13.5) Neonatal death 0.6 (0.2–1.6) 0.7 (0.3–2) 4.8 (1.7–13.8)*

Abbreviations: CI, confidence intervals; MAS, meconium aspiration syndrome; NICU, neonatal intensive care unit; OR, odds ratios. *P<0.05 as compared with 39 weeks’ gestation pregnancies. of gestation advanced beyond 39 weeks. This finding has previously complications for the baby, but also for the maternal obstetric been reported; thus, in a population-based cohort study, Ross complications at the time of birth. et al.10 reported that the risk of post-term pregnancy in obese There were additional adverse perinatal outcomes associated women was almost doubled, compared with normal weight women. exclusively with pregnancies at 42–44 weeks’ gestation: fetal and Nutrition counseling should be offered to women in reproductive neonatal death, meconium aspiration syndrome and need of age to promote better reproductive outcomes. special care at birth. Appropriate and individualized intervention to Among this cohort of pregnant women belonging to a prevent prolonged (>42 weeks) pregnancies might result in a heterogeneous population seeking care at nine different hospitals fourfold improvement in perinatal survival, as well as a decrease in in Mexico, the rate of several perinatal complications was observed respiratory morbidity such as meconium aspiration syndrome in to increase as early as 40 weeks of gestation, when compared with this population. 39 weeks gestation pregnancies. In this study, the association found between a prolongation of The frequency of preeclampsia and chorioamnionitis was higher pregnancy and acute fetal distress and fetal and neonatal deaths as pregnancy advanced beyond 39 weeks. Thus, the odds of suggests that these findings are mostly related to asphyxia at the chorioamnionitis were 1.4, 2 and 2.8 higher for pregnancies 40, 41 time of birth. This might be related to placental dysfunction or and 42 to 44 weeks, respectively, as compared with 39 weeks’ some other complication that merits additional investigation. pregnancies. Caughey et al.,11 in a study that included more The limitations of this study are the retrospective nature of the than 100, 000 pregnant women, reported that the rate of data and missing potential cofounders (for example weight and chorioamnionitis also increased beyond 39 weeks’ gestation height were self-reported and could not be recollected in (odds ratio when comparing to 39 weeks gestation, 1.3 and 1.7, approximately half of the cases); the denominator used was all for 40 and 42 to 44 weeks’ gestation, respectively). pregnancies delivered at study hospitals with no differentiation Of concern is the fact that approximately half of pregnancies between those delivered for the outcomes of preeclampsia and beyond 39 weeks were delivered by emergency cesarean section (1.4 stillbirth or those pregnancies at risk and finally, about 35% of the to 1.8 times higher than that observed at 39 weeks). These risks gestational ages were determined by dates, the inexact nature of persisted when controlled for potential cofounders. Caughey et al.11 dating used in this paper probably biased the results away from reported that the incidence of emergency cesarean section also the null, meaning that with solid ultrasound dating, the findings increased beyond 39 weeks of gestation, odds ratio 1.8, 2 and 2.1 would be even more striking. for 40, 41 and 42 to 44 weeks, respectively, as compared with 39 weeks pregnancies. These findings warrant attention and indicate that these pregnancies need to be closely monitored. Conclusion Babies born as early as 40 weeks’ gestation had twice the risk of From these findings, fetal-maternal surveillance is highly macrosomia as those delivered at 39 weeks, and the risk increased recommended as early as 40 weeks’ gestation and an individualized seven times at 42 to 44 weeks’ gestation pregnancies. This is an approach needs to be performed to promote induction of labor important problem, not only for the short- and long-term when appropriate. However, the use of labor induction to

Journal of Perinatology Perinatal complications in late-term and post-term pregnancies AM De los Santos-Garate et al 793 encourage delivery on or around 39 weeks should be tested within 3 Cheng YW, Nicholson JM, Nakagawa S, Bruckner TA, Washington E, Caugehy AB. the context of a randomized clinical trial. Perinatal outcomes in low-risk term pregnancies: do they differ by week of gestation? Am J Obstet Gynecol 2008; 199: 370.e1–370.e7. 4 Caughey AB, Musci TJ. Complications of term pregnancies beyond 37 weeks of Conflict of interest gestation. Obstet Gynecol 2004; 103: 57–62. 5 Caughey AB, Washington E, Laros R. Neonatal complications of term pregnancy: rates The authors declare no conflict of interest. by gestational age increase in a continuous, not threshold, fashion. Am J Obstet Gynecol 2005; 192: 185–190. 6 Ballard JL, Khoury JC, Wedig K, Wang L, Filers-Walsman BL, Lipp R. New Ballard Score, Acknowledgments expanded to include extremely premature infants. JPediatr1991; 119: 417–423. The authors are grateful to Alfonso Reyes for his assistance in data analyses, John 7 Capurro H, Konichezky S, Fonseca D, Caldeyro-Barcia R. A simplified method for Kasik for his critical review of the manuscript and Ana Carla Arguëlles Albarrań diagnosis of gestational age in the newborn infant. J Pediatr 1978; 93: 120–122. 8 Cunningham F, MacDonald P, Gant N, Leveno K, Gilstrap III L. Embarazo prete´rmino for secretarial assistance. y poste´rmino y retraso del crecimiento fetal. In, Williams Obstetricia. 4th edition. Barcelona: Masson SA; 1996: 839–867. References 9 Caughey AB, Stotland NE, Washington AE, Escobar GJ. Maternal and obstetric complications of pregnancy are associated with increasing gestational age at term. Am 1 Caughey AB, Stotland NE, Washington AE, Escobar GJ. Who is at risk for J Obstet Gynecol 2007; 196: 155.e1–155.e6. prolonged and postterm pregnancy? Am J Obstet Gynecol 2009; 200: 10 Ross N, Sahlin L, Ekman-Ordeberg G, Kieller H, Stephansson O. Maternal risk factors 683.e1–683.e5. for postterm pregnancy and cesarean delivery following labor induction. Acta Obstet 2 Olesen A, Westergaard J, Olsen J. Perinatal and maternal complications related to Gynecol Scand 2010; 89: 1003–1010. postterm delivery: a national register-based study, 1978-1993. Am J Obstet Gynecol 11 Caughey AB, Bishop JT. Maternal complications of pregnancy increased beyond 40 2003; 189: 222–227. weeks of gestation in low risk women. J Perinatol 2006; 26: 540–545.

Appendix Participants of NEOSANO’s Perinatal Network: Dr Jose Iglesias and Dr Isabel Berna´rdez; Hospital Espan˜ol, Dr Lino Cardiel and Dr Edgar Reynoso; Hospital General de Mexico City. Dr Jose Hernandez; Hospital Medica Sur, Mexico City. Me´xico, Mexico City. Dr Ana Limo´n Rojas; Hospital Pemex Sur, Dr Jesus Salcedo Hospital Valdivieso, Oaxaca City, Oaxaca. Mexico City. Dr Alberto Orozco and Dr Sergio Graham; Hospital Dr Livia Flores, Dr Roberto Tepatzi; Hospital General, Hospital Angeles Pedregal, Mexico City. Santa Ana, Hospital Apizaco, Tlaxcala City, Tlaxcala.

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