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ORIGINAL RESEARCH |
From the Latin American Center for Perinatology and Human Development, Division of Health Promotion and Protection, Pan American Health Organization, World Health Organization, Montevideo, Uruguay, and Department of Women’s and Children’s Health Section of International Maternal and Child Health, University of Uppsala, Stockholm, Sweden.
Address reprint requests to: Agustin Conde-Agudelo, MD Hospital de Clinicas, piso 16 Casilla de Correo 627 11000 Montevideo Uruguay E-mail: condeagu{at}clap.ops-oms.org
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Abstract |
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Methods: We studied the association between multiple gestation and frequency of adverse maternal outcomes in 885,338 pregnancies recorded in the Perinatal Information System database of the Latin American Center for Perinatology and Human Development, Montevideo, Uruguay, between 1985 and 1997. Relative risks (RRs) were adjusted for 14 potential confounding factors through multiple logistic regression models.
Results: There were 15,484 multiple gestations. Among parous women, multiple gestation was associated with a twofold increase in risk of death compared with singleton gestations [adjusted RR 2.1; 95% confidence interval (CI) 1.1, 3.9]. Compared with singleton gestations, women with multiple gestations had adjusted RRs of 3.0 (95% CI, 2.9, 3.3) for eclampsia, 2.2 (95% CI, 1.9, 2.5) for preeclampsia, and 2.0 (95% CI, 1.9, 2.0) for postpartum hemorrhage. Likewise, there was significant association between multiple gestation and increased incidence of preterm labor, anemia, urinary tract infection, puerperal endometritis, and cesarean delivery. The incidences of premature rupture of membranes, third-trimester bleeding, and gestational diabetes mellitus were not statistically different for singleton and multiple gestations.
Conclusion: Multiple gestation increases the risk of significant maternal morbidity and mortality.
Recent reports from developed countries indicate that the incidence of multiple birth has increased during the past 20 years.1,2 In the United States, between 1980 and 1996, the twin gestation rate increased by 47% and the triplet and higher-order gestation rate quadrupled.2 This dramatic rise in multiple gestations, and especially in higher-order multiple gestations, has been attributed to the increasing availability of ovulation-inducing agents, use of assisted-reproductive technologies, and a shift toward bearing children at older maternal ages when multiples are more likely to occur naturally.1
Traditionally, multiple gestations have been associated with increased incidence of adverse pregnancy outcomes.3 Although perinatal and neonatal morbidity and mortality associated with multiple gestations have been well documented, little is known about the effects of such gestations on maternal mortality and morbidity. The literature on relationships between multiple gestation and adverse maternal outcomes consists mainly of small studies,4–6 which present either few data on maternal outcomes or mention such outcomes as only a minor part of an overall study. Most of those studies also did not adjust their estimates for potentially confounding factors such as maternal age, parity, and body mass index (BMI), which have been associated with multiple gestations and adverse maternal outcomes.7
We did this investigation to test the hypothesis that the risk of adverse maternal outcomes is higher among women with multiple gestations compared with women with singleton gestations. We also compared adverse maternal outcomes between multiple and singleton gestations by parity.
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Materials and Methods |
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From 1985 through 1997, the Perinatal Information System database recorded 1,008,954 gestations of women who were born in Uruguay (25.3%), Argentina (24.1%), Peru (9.4%), Colombia (8.6%), Honduras (8.2%), Paraguay (6.9%), El Salvador (4.2%), Chile (2.8%), Bolivia (2.3%), Costa Rica (2.2%), Panama (1.4%), Dominican Republic (1.3%), Nicaragua (1.2%), Brazil (0.8%), Ecuador (0.6%), Mexico (0.4%), Bahamas (0.2%), and Venezuela (0.1%). Descriptions of the database have been published elsewhere.8,9 From the first antenatal visit until discharge of mother and neonate, the attendant physicians or nurses collect data in the perinatal clinical record in check-box format, which includes demographic information, reproductive history, maternal characteristics, prenatal care, labor management, maternal complications during pregnancy, delivery, the puerperium, and neonatal outcomes. Then, data are entered in an on-site computer and quality control is done. Later they are sent to the Latin American Center for Perinatology and Human Development, where further data entry, quality control check, and validation are done.
We included all pregnancies that ended in live births and stillbirths of at least 20 weeks’ gestation. The term "multiple gestation" refers to gestations with two or more fetuses. Adverse maternal outcomes were classified according to the English version of the International Classification of Diseases, tenth revision (ICD-10).10 Preeclampsia and eclampsia were coded as ICD-10 codes O14 and O15, respectively. Third-trimester bleeding included placenta previa with hemorrhage (ICD-10 code O44.1) and abruptio placentae (ICD-10 code O45). Cesarean delivery included single delivery by cesarean (ICD-10 code O82), multiple delivery, all by cesarean (ICD-10 code O84.2), and multiple delivery by combination of cesarean and other methods (ICD-10 code O84.8). Urinary tract infection, anemia, preterm labor, premature rupture of membranes, gestational diabetes mellitus, postpartum hemorrhage, and puerperal endometritis were coded as ICD-10 codes O23, O99.0, O60, O42, O24.4, O72, and O85, respectively. Maternal death was defined as the death of a woman while pregnant or within 42 days after delivery, from any cause related to or aggravated by gestation or its treatment, but not from accidental or incidental causes.
Significant trend (P < .05) across the groups was determined using the 
2 test with k - 1 degrees of freedom.11 Estimates of crude relative risk (RR) with 95% confidence intervals (CIs) were computed as measures of the association between multiple gestation and adverse maternal outcomes. Adjusted odds ratios (ORs) were derived through logistic regression models as estimates of adjusted RRs. Multiple logistic regression analysis was used to evaluate the association between multiple gestation and adverse maternal outcomes. The estimates were adjusted for maternal age, parity, marital status, education, smoking, height, prepregnancy weight, prepregnancy BMI, history of hypertension, trimester in which prenatal care was started, number of prenatal care visits, geographic area (Andean region, Central America, and Southern cone), hospital type (tertiary, regional, and community hospitals), and year of delivery (1985–1989, 1990–1994, 1995–1997). Moreover, interactions among adverse maternal outcomes were tested by incorporation of some of them as possible confounders into the logistic regression models. The effects of multiple gestation on adverse maternal outcomes also are presented separately for nulliparous and parous women.
Information on prepregnancy BMI was missing for 36% of the women, so several models were constructed to assess the effects of adjustment for that variable for each adverse maternal outcome. The first model was based on the entire data set, without adjustment for BMI. The second was based on the women for whom data on BMI were available, but without adjustment for it. The third was based on the women with data on BMI and with adjustment for it. That approach allowed us to determine whether the inclusion of BMI in the model altered the effects of multiple gestation on adverse maternal outcomes. In the several multivariate analyses, we found no evidence of confounding of the effects of multiple gestation by BMI. The patterns yielded were similar, although the widths of the CIs slightly increased. All analyses used the SPSS 8.0 program package (SPSS Inc., Chicago, IL)
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Results |
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). Multiparity was associated with a 20% increase in the risk of multiple gestation compared with nulliparous women. There was a significant trend toward increasing risk of multiple gestation with higher prepregnancy BMI (2 test for trend = 35.6 with three degrees of freedom; P < .001). Women with familial histories of twin gestations were almost three times as likely to have multiple gestations compared with women who did not have such histories. The risk of multiple gestation was unrelated to history of abortion. The mean gestational age at delivery was significantly lower for multiples than singletons (36.0 ± 3.8 versus 38.2 ± 4.6 weeks, respectively; P < .001).
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. The incidences of preeclampsia, eclampsia, preterm labor, anemia, urinary tract infection, postpartum hemorrhage, puerperal endometritis, premature rupture of membranes, third-trimester bleeding, cesarean delivery, and gestational diabetes mellitus were significantly greater in multiple than singleton gestations. The maternal fatality rate (per 10,000 women) was 7.8 for multiple gestations compared with 4.3 for singleton gestations. However, this difference was only marginally significant (P = .053).
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). The risk of preterm labor was almost four times greater among multiple than singleton gestations. There also was a significant association between multiple gestation and increased incidence of anemia, urinary tract infection, postpartum hemorrhage, and puerperal infection. Cesarean rate for multiple gestations was increased 2.5 times above singleton rate and women carrying multiples were also subject to a higher risk of developing preeclampsia and eclampsia than women carrying singletons. Forty-one percent of cases of preeclampsia in multiple gestations occurred before 37 weeks’ gestation compared with 17% in singleton gestations (P < .001).
We further examined the association between multiple gestation and adverse maternal outcomes after stratifying for parity (Table 3). Parous women carrying multiples had a twofold increase in risk of death compared with multiparas carrying singletons. The risks for preeclampsia, eclampsia, preterm labor, anemia, postpartum hemorrhage, puerperal endometritis, PROM, and cesarean delivery were higher in nulliparous women with multiple gestations than multiparous women with multiple gestations. Gestational diabetes mellitus, third-trimester bleeding, and urinary tract infections were higher among multiparous women with multiple gestations. We observed an additive effect of multiple gestation and nulliparity for risk of eclampsia. The risk of eclampsia was almost eight times higher for nulliparas with multiple gestations than parous women with singleton gestations (adjusted RR 7.9; 95% CI 5.8, 10.8). A similar pattern was observed for preterm labor.
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Discussion |
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Few studies have explored the association between multiple gestation and maternal mortality. Three studies from African countries found an increased risk of maternal death associated with multiple gestation.4–6 The RRs for such association in those studies ranged between 2.1 and 6.9. A recent population-based study13 from 13 European countries on maternal mortality found an OR of 2.9 (95% CI, 1.4, 6.1) for multiple compared with singleton gestations. However, none of those studies examined association between maternal mortality and multiple gestation according to parity. In the Nigerian study,4 14 of 16 multiple gestation–associated maternal deaths occurred among parous women, but estimates of RRs by parity were not calculated. We observed that only parous women carrying multiples were at greater risk of death than women carrying singletons. The lack of association between maternal death and nulliparous multiple gestation in the present study might be a question of power because of the small number of maternal deaths in that group.
Our study corroborates the findings from reports that women who carried multiples are at increased risk of preterm labor,14 preeclampsia-eclampsia,15 postpartum hemorrhage,16 puerperal infection,17 anemia,4,5 urinary tract infection,18 and cesarean delivery.19 Several reasons have been offered to explain those associations. The most probable etiology of premature labor in multiple gestation is uterine overdistention, although insufficiency of uterine blood flow has also been implicated.20 The higher incidence of preeclampsia has been related to a larger placenta in multiple gestations, which exposes the mother to more paternal antigen.21 The expanded maternal blood volume plus the increased demand of the fetus for folic acid and iron contribute to the increased frequency of anemia.22 A larger placental bed and cesarean delivery,17 uterine atony caused by sudden decompression of the overdistended uterus,23 and more prominent physiologic hydroureter and hydronephrosis in multiple gestation24 seem to be associated with puerperal endometritis, postpartum hemorrhage, and urinary tract infection, respectively.
Some studies found increased incidence of gestational diabetes mellitus among women with multiple gestations,25 whereas others found no increase.26 Levels of insulin antagonists such as human placental lactogen, estrogen, and progesterone are higher in multiple than singleton gestations, so some authors have hypothesized that the incidence of gestational diabetes mellitus would be increased in multiple gestations.25 In spite of those concerns, we found no association between multiple gestation and gestational diabetes mellitus. However, that finding must be interpreted with caution because we did not know if gestational diabetes mellitus was systematically looked for in singleton and multiple gestations to the same extent. We also did not confirm associations between multiple gestations and PROM and third-trimester bleeding, as suggested by other authors.27,28
Several limitations and potential biases of this study must be considered. Our findings might be limited by underreporting of complications of pregnancy, labor, and puerperium in perinatal records. The accuracy of specific diagnoses registered in our database also has not been extensively checked and only local medical record verifications were done.29 Therefore, our data are limited to a certain extent. However, overall rates of adverse maternal outcomes in this data set were similar to those reported in other studies, which would add support to the accuracy of diagnoses. Our results also came from developing countries, hence caution should be used when generalizing our results to other populations. That limitation is unlikely to have an effect because most of the associations identified in the present study were described in reports from developed countries. Because 99.5% of multiple deliveries in our population were in hospitals, maternal risks probably are less than in most developing country situations when multiples are not diagnosed in more than about half,30 and even then cannot always be transferred to institutions. Our study was not population-based, but it was based in several different hospitals across Latin America and the Caribbean. It is unlikely that factor confounded the effects of multiple gestation on maternal morbidity because the results were similar among countries considered. The few maternal deaths did not allow us to analyze by country. Uruguay and Argentina contributed almost half of the births in our database, so our results might not be generalizable to the entire Latin American population. Even though we adjusted for several factors, there is still potential for confounding and bias by other unknown factors.
There was a rise in multiple gestations, in proportion to singleton gestations and in absolute numbers, so the associated higher frequency of maternal morbidity and mortality is of great importance. We agree with Blickstein31 that multiple gestations should be included among risk factors for maternal mortality, and specific multidisciplinary antepartum programs for women with multiple gestations should be available in all settings. Women carrying multiple gestations must be advised of the potential harm. Besides the effect on maternal health, the high rate of adverse maternal outcomes seen with multiple gestations also might have significant economic implications, and it should be taken into account when estimating health care costs associated with such gestations. Our findings, with well-known increased risk of neonatal morbidity and mortality among multiple gestations, should focus attention on indiscriminate use of ovulation-inducing agents and assisted-reproductive technologies that raise the rate of multiple gestations.
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Footnotes |
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Received August 18, 1999. Received in revised form November 19, 1999. Accepted December 2, 1999.
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2. Guyer B, MacDorman MF, Martin JA, Peters KD, Strobino DM. Annual summary of vital statistics—1997. Pediatrics 1998;102: 1333–49.
3. Multifetal gestation. In: Cunningham FC, MacDonald PC, Gant NF, Leveno KJ, Gilstrap LC, eds. Williams obstetrics, 19th ed. Norwalk, CT: Appleton & Lange, 1993:891–918.
4. Harrison KA. Child-bearing, health, and social priorities: A survey of 22,774 consecutive hospital births in Zaria, Northern Nigeria. Multiple gestation. Br J Obstet Gynaecol 1985;92:49–60.
5. Picaud A, Nlome-Nze R, Ogowet-Igumu N, Faye A, Mba Allo L. Perinatal and maternal risks in multiple pregnancies. Rev Fr Gynecol Obstet 1989;84:381–91.[Medline]
6. McDermott JM, Steketee R, Wirima J. Mortality associated with multiple gestation in Malawi. Int J Epidemiol 1995;24:413–9.
7. MacGillivray I, Campbell DM. The physical characteristics and adaptation of women with twin gestation. In: Nance WE, ed. Twin research: Clinical studies. New York: Alan R Liss, 1978:81–6.
8. Diaz-Rosello JL. Health services research, outcomes, and perinatal information systems. Curr Opin Pediatr 1998;10:117–22.[Medline]
9. Simini F. Perinatal information system (SIP): A clinical database in Latin America and the Caribbean. Lancet 1999;354:75.[Medline]
10. English version of International Classification of Diseases, 10th rev. Geneva, Switzerland: World Health Organization, 1992.
11. Altman DG. Practical statistics for medical research. London: Chapman & Hall, 1990:261–2.
12. Okonofua FE. The case against new reproductive technologies in developing countries. Br J Obstet Gynaecol 1996;103:957–62.[Medline]
13. Senat MV, Ancel PY, Bouvier-Colle MH, Bréart G. How does multiple gestation affect maternal mortality and morbidity? Clin Obstet Gynecol 1998;41:79–83.
14. Kiely JL. What is the population-based risk of preterm birth among twins and other multiples? Clin Obstet Gynecol 1998;41:3–11.[Medline]
15. Coonrod DV, Hickok DE, Zhu K, Easterling TR, Daling JR. Risk factors for preeclampsia in twin gestations: A population-based cohort study. Obstet Gynecol 1995;85:645–50.[Abstract]
16. Combs CA, Murphy EL, Laros RK Jr. Factors associated with postpartum hemorrhage with vaginal birth. Obstet Gynecol 1991; 77:69–76.
17. Alexander JM, Gilstrap LC III, Cox SM, Ramin SM. The relationship of infection to method of delivery in twin gestation. Am J Obstet Gynecol 1997;177:1063–6.[Medline]
18. Kauppila A, Jouppila P, Koivisto M, Moilanen I, Ylikorkala O.Twin gestation. A clinical study of 335 cases. Acta Obstet Gynecol Scand Suppl 1975;44:5–12.
19. Benachi A, Pons JC. Is the route of delivery a meaningful issue in twins? Clin Obstet Gynecol 1998;41:31–5.
20. Powers WF. Twin gestation. Complications and treatment. Obstet Gynecol 1973;42:795–808.
21. Scott JS. Gestation toxaemia associated with hydrops fetalis, hydatidiform mole and hydramnios. J Obstet Gynaecol Br Emp 1958; 65:689–701.[Medline]
22. Hall MH, Campbell DM, Davidson RJ. Anemia in twin gestation. Acta Genet Med Gemellol 1979;28:279–82.[Medline]
23. Spellacy WN. Twin gestation. In: Scott JR, ed. Danforth’s Obstetrics & Gynecology, 7th ed. Philadelphia: Lippincott-Raven Publishers, 1994:335–6.
24. Yeast JD. Maternal physiologic adaptation to twin gestation. Clin Obstet Gynecol 1990;33:10–7.[Medline]
25. Roach VJ, Lau TK, Wilson D, Rogers MS. The incidence of gestational diabetes in multiple pregnancy. Aust N Z J Obstet Gynaecol 1998;38:56–7.[Medline]
26. Naidoo L, Jailal I, Moodley J, Desai R. Intravenous glucose tolerance test in women with twin gestation. Obstet Gynecol 1985;66:500–2.
27. Mercer BM, Goldenberg RL, Iams JD, Meis PJ, Caritis SN, Thurnau GR, et al. The preterm prediction study: Analysis of risk factors for preterm premature rupture of the membranes. J Soc Gynecol Invest 1996;3:350A.
28. Makhseed M, Al-Sharhan M, Egbase P, Al-Essa M, Grudzinskas JG. Maternal and perinatal outcomes of multiple gestation following IVF-ET. Int J Gynecol Obstet 1998;61:155–63.[Medline]
29. Cobo E. Aplicación de un modelo de historia clínica perinatal. Rev Col Obstet Ginecol 1985;36:79–94.
30. MacGillivray I, Nylander PPS, Corney G. Human multiple reproduction. Philadelphia: WB Saunders, 1975:107–15.
31. Blickstein I. Maternal mortality in twin gestations. J Reprod Med 1997;42:680–4.[Medline]
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