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Pregnancy, delivery and perinatal outcome in female survivors of polio
Journal of the Neurological Sciences 258 (2007) 27 – 32 www.elsevier.com/locate/jns
Pregnancy, delivery and perinatal outcome in female survivors of polio Gyri Veiby a,c,⁎, Anne Kjersti Daltveit b,d , Nils Erik Gilhus a,c a
b
Department of Clinical Medicine, Section for Neurology, University of Bergen, Norway Department of Public Health and Primary Health Care, Section for Epidemiology and Medical Statistics, University of Bergen, Norway c Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway d Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway Received 3 July 2006; received in revised form 5 February 2007; accepted 12 February 2007 Available online 29 March 2007
Abstract Objective: To investigate possible effects on pregnancy, delivery and perinatal outcome in female survivors of polio. Methods: In a cohort design, data from the national population based Medical Birth Registry of Norway (MBRN) were used to compare all 2495 births recorded 1967–1998 by female survivors of polio with all 1.9 mill non-polio deliveries. The results were adjusted for time period, maternal age, and birth order by unconditional logistic regression, with effects presented as adjusted Odds Ratios (OR) with a corresponding 95% Confidence Interval (CI) and p values. Results: Female polio survivors had a higher occurrence of pre-eclampsia (3.4% vs. 2.8%, p = 0.003, OR = 1.4, CI = 1.1–1.7), gestational proteinuria (1.3% vs. 0.5%, p < 0.001, OR = 2.0, CI = 1.4–2.8), renal disease prior to pregnancy (1.4% vs. 0.9%, p = 0.001, OR = 1.8, CI = 1.2– 2.5), vaginal bleeding (3.8% vs. 2.0%, p < 0.001, OR = 1.7, CI = 1.4–2.1), and urinary tract infection during pregnancy (3.5% vs. 2.4%, p < 0.001, OR = 1.7, CI = 1.4–2.1). Deliveries complicated by obstruction of the birth process were more common in the polio group (6.1% vs. 2.0%, p < 0.001, OR = 4.8, CI = 4.0–5.6), and cesarean section was performed at a higher rate throughout the time period (13.2% vs. 8.3%, p < 0.001, OR = 2.7, CI = 2.4–3.1). Infants of polio mothers had a lower mean birth weight (3383 g vs. 3483 g, p < 0.001), and more often had a birth weight below 2500 g (6.9% vs. 5.2%, p = 0.001, OR = 1.3, CI = 1.1–1.5). There was no difference regarding pregnancy length. The risk of perinatal death was increased (2.1% vs. 1.1%, p = 0.05, OR = 1.3, CI = 1.0–1.7). Conclusion: Pregnancy in female survivors of polio is associated with an increased risk for complications during pregnancy and delivery, as well as an adverse perinatal outcome. Awareness towards risk factors should improve pre-natal care and possibly prevent complications. © 2007 Elsevier B.V. All rights reserved. Keywords: Polio; Pregnancy; Delivery; Cesarean section; Pre-eclampsia; Perinatal outcome
1. Introduction Patients with former polio experience difficulties later in life due to sequels after the acute illness. Complications during pregnancy and birth can be related to long-term effects of polio. The polio virus spreads through the orofecal route, and can infect the anterior horn motor neurons of the spinal cord producing an acute flaccid paralysis [1,2]. Muscle weakness ⁎ Corresponding author. Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway. Tel.: +47 55 97 50 00. E-mail address: [email protected] (G. Veiby). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.02.019
occur in 1–2% of infected persons during the acute illness [3], and is followed by a post-paralytic phase. Nearly 50% of those with acute muscle weakness develop post-paralytic permanent loss of motor function [2,4], affecting limbs, truncal and respiratory muscles. The lower limbs are most frequently affected. Global polio surveillance is incomplete, but has improved over the years. A total of 10 872 cases of confirmed paralytic polio has been reported since the year 2000 [5]. Vaccination programs have eradicated the large epidemics, but still there are outbreaks of paralytic polio in countries and areas where vaccination is insufficient [6,7]. Estimation of global polio incidence during the 1980's indicated 200,000–250,000
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annual cases of paralytic polio [8]. The majority acquired polio in early life. Thus, there is a considerable amount worldwide of women in childbearing age with polio related disability. In Norway, epidemics occurred during the 20th century until the vaccine was introduced in 1954. An estimate of 5000–10,000 persons are still living with poliorelated disability in Norway [4]. The aim of this study was to explore if female survivors of polio experience more complications during pregnancy and birth, and how such complications correlate to pregnancy risk factors. These obstetric risks should be known by public health officials in areas of the world where polio outbreaks have occurred during the last three decades. However, this information is difficult to obtain in poor countries with an inadequate infrastructure or ongoing political conflict. The national birth registry of Norway represents a unique tool to identify and examine a cohort of polio survivors during pregnancy. 2. Materials and methods 2.1. Patient selection Patients were identified through the Medical Birth Registry of Norway (MBRN), a national registry established in 1967, based on the compulsory notification of all births at 16 or more weeks of gestation. The registry contains medical data on the mother's health before and during pregnancy, on delivery, and on the newborn. A standardized notification form is filled in by the patient's attending physician and midwife, and sent within 9 days after discharge from the hospital. Diagnoses recorded before discharge from the birth institution are noted, and the text in the notification form is coded at MBRN partly according to the International Classification of Diseases, 8th Revision (ICD-8), and partly according to a coding system developed for the registry. MBRN is placed under the Norwegian Institute of Public Health. Complete ascertainment of all births is ensured through a record linkage to the National Population Registry, based on the unique identification number of all inhabitants of Norway. Our study included all deliveries registered between January 1, 1967 and December 31, 1998. An unchanged notification form was used during this period of time. As the last significant epidemic outbreaks of polio in Norway took place in 1950–1954, we chose not to include births after 1998. Inclusion criteria were defined as all deliveries by women diagnosed with previous polio according to ICD-8 criteria. The polio group consisted of 2495 births by 1758 women. In the majority, the polio-related disability was not further characterized. The reference group consisted of all 1.9 mill deliveries by women without a registered diagnosis of polio. Within the polio group, 60% of deliveries occurred in 1967–1974, 23% in 1975–1979, and 16% in 1980–1998. The corresponding distribution of non-polio births was 28%, 14%, and 58%.
2.2. Variables The selected variables have been defined by MBRN after consensus among obstetricians, neonatologists and epidemiologists. Demographic variables included age of mother in completed years, the infant's birth order, and type of obstetric institution. Risk factors associated with adverse pregnancy outcome were selected [9,10]: Hypertension, diabetes mellitus, chronic cardiac disease, rheumatic disease, and chronic kidney disease. Outcome measures for pregnancy, obstetrical complications, and the newborn were also selected a priori. Pregnancy complications included: Diabetes mellitus, urinary tract infection, pre-eclampsia, gestational proteinuria (proteinuria detected for the first time during pregnancy), pregnancyinduced hypertension (with/without edema), vaginal hemorrhage, and placental abruption. Pre-eclampsia was defined as proteinuria combined with pregnancy-induced hypertension or threatening eclampsia. Pregnancy-induced hypertension without proteinuria is not included in MBRN's current definition of pre-eclampsia. Obstetrical complications included: Induction of labor (augmentation of delivery not included), presentation anomalies, obstruction of birth process (mechanical obstruction of the fetus passing the birth canal), functional disturbance of birth process (atonia uteri, threatening uterine rupture, dystocia cervix uteri, prolonged labor, slow progression of 2nd stage, secondary delayed contractions, or rapid labor), uterine rupture, birth canal injuries, postpartum vaginal hemorrhage (> 500 ml), and intervention during birth (any intervention, cesarean section, forceps, or vacuum). The classification of cesarean sections into elective or emergency procedure was introduced in 1989. Perinatal outcome included: Gestational age in completed weeks, birth weight in grams, complicating neonatal conditions (birth weight < 2500 g, gestational age < 37 weeks, Apgar score < 7 at 1 min and 5 min, and asphyxia during delivery), transfer of the newborn to a pediatric ward, birth defects, and mortality (stillbirth, perinatal mortality). Birth defects were defined as severe or not severe according to a definition by MBRN based on ICD-8. Stillbirths consisted of all fetal deaths ≥ 16 weeks of gestation, occurring before or during birth. Perinatal mortality included all deaths occurring during the first 6 days in live born children ≥ 16 weeks of gestation, and all stillbirths ≥ 28 weeks of gestation (if unknown age of gestation: birth weight > 1000 g/birth length > 35 cm). 2.3. Statistics The analyses were based on crude, stratified and adjusted measures, and were performed by SPSS for Windows. Twosided p values < 0.05 were considered as statistical significant. Arithmetic mean was calculated for maternal age, birth order, gestational length, and birth weight, and analyzed by independent samples T tests to compare the polio and the
G. Veiby et al. / Journal of the Neurological Sciences 258 (2007) 27–32
reference group. Crosstabulated measures with expected cell count less than 5 were evaluated by exact tests based on paper by Vollset and Hirji [11]. All other variables were adjusted by unconditional logistic regression (potential confounding factors represented as categorical variables), and results are presented as adjusted Odds Ratios with corresponding 95% Confidence Intervals and p values. Period of time (1967–1974, 1975–1979, 1980–1998), maternal age (< 25, 25–29, 30–34, 35+ years) and birth order (first, second, third or more) were considered potential confounders or effect modifiers. We also included year of birth as a linear term in the model, but this had minimal impact on the outcomes, and is not included in the presented results. Effect modification was evaluated by Breslow–Days test. The periods of time were selected based on known polio-epidemics in Norway. Operative interventions during labor have changed during our recording period [12–14], and are presented separately for each time period. 3. Results
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Table 1 Pregnancy and obstetrical complications in the polio (n = 2495) and reference (n = 1,866 885) group Complication Hypertension, pregnancy-induced Pre-eclampsia Urinary tract infection during pregnancy Gestational proteinuria Vaginal bleeding during pregnancy Induction of delivery Presentation anomalies Obstruction of birth process Functional disturbance of birth process Rupture of the uterus b Birth canal injuries c Postpartum vaginal hemorrhage >500 ml
Polio n (%)
Reference p (%) value a 0.3
OR a (CI)
40 (1.6)
1.3
1.2 (0.9–1.6)
85 (3.4) 88 (3.5)
2.8 2.4
0.003 1.4 (1.1–1.7) <0.001 1.7 (1.4–2.1)
33 (1.3) 95 (3.8)
0.5 2.0
<0.001 2.0 (1.4–2.8) <0.001 1.7 (1.4–2.1)
441 (17.7) 13.4 121 (4.8) 4.7 152 (6.1) 2.0
<0.001 1.4 (1.2–1.5) 0.2 1.1 (0.9–1.4) <0.001 4.8 (4.0–5.6)
160 (6.4)
6.6
0.01
1.2 (1.0–1.5)
2 (0.1) 39 (1.8) 122 (4.9)
0.014 2.6 4.9
0.06 0.9 0.3
5.7 (0.9–19) 1.0 (0.7–1.3) 1.1 (0.9–1.3)
a
3.1. Demographic characteristics The mean maternal age in the polio group was 28.0 vs. 26.8 years in the reference group (p < 0.001). As the mean age and birth order differed significantly between the groups; all comparisons have been adjusted for this difference. A higher percentage of women in the polio group gave birth at a university hospital (29.6% vs. 24.9%, p < 0.001).
All p values and Odds Ratios (OR) with 95% Confidence Interval (CI) are adjusted for time period, maternal age and birth order. b Expected cell count <5: p value and corresponding OR with 95% CI is calculated by 2-sided exact test. c Deliveries by cesarean section not included.
The groups were similar regarding pregnancy–diabetes, preterm rupture of amniotic membranes and placental abruption.
3.2. Pregnancy complications
3.3. Obstetrical complications
Pre-eclampsia, gestational proteinuria, and urinary tract infection during pregnancy was more common in the polio group (Table 1). Pregnancy-induced hypertension did not differ significantly between the groups. However, when pregnancy-induced hypertension with edema, gestational proteinuria and pre-eclampsia were all combined, the total occurrence was clearly increased in the polio group (5.3% vs. 3.6%, p < 0.001, OR = 1.5, CI = 1.3–1.8). As chronic kidney disease increases the risk for preeclampsia [15], a comparison was made between women with and without such disease. As expected, the renal patients demonstrated a higher rate of pre-eclampsia in both the polio (p = 0.04, OR = 3.7) and the reference group (p < 0.001, OR = 1.5). When women with renal disease were excluded from the material, pre-eclampsia was still more common in the polio group (3.3% vs. 2.8%, p = 0.006, OR = 1.4, CI = 1.1–1.7). Vaginal bleeding occurred at a higher rate in the polio group (Table 1), this difference being confined to the first (p < 0.001, OR = 1.8, CI = 1.4–2.4) and second trimester (p < 0.001, OR = 2.1, CI = 1.4–3.2). An exclusion of such pregnancies from the material did not change the major perinatal outcomes in the polio group (low birth weight, low gestational age, perinatal death).
Polio patients more often experienced deliveries complicated by obstruction of the birth process (Table 1), and this occurred in a much higher proportion of cesarean sections compared to the reference group (44% vs. 23%, p < 0.001, OR = 2.6, CI = 2.1–3.2). Two polio mothers experienced uterine rupture during delivery, both with stillborn outcome. The overall rate of presentation anomalies was similar in the two groups, but at maternal age > 34 years there was a difference, mainly due to breech presentations in the polio group (7.6%, n = 26 vs. 3.7%, p < 0.001, OR = 2.1, CI = 1.4– 3.2). The significant difference between the groups for functional disturbance of the birth process (Table 1) was confined to the first time period (5.9%, n = 88 vs. 3.6%, p = 0.003, OR = 1.4, CI = 1.1–1.7). 3.4. Obstetrical interventions A higher frequency of interventions during birth occurred in the polio compared to the reference group (Table 2). There was a marked difference for cesarean sections (13.2% vs. 8.3%, p < 0.001, OR = 2.7, CI = 2.4–3.1), and this difference increased throughout the period (Fig. 1). Data from 1989 and onwards showed a higher number of elective in proportion to
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Table 2 Interventions during birth in the polio and reference group
Table 3 Birth outcome and neonatal complications in the polio and reference group
Reference %
p value a
OR a (CI)
Any intervention 1967–1974 327 (21.8) 1975–1979 153 (26.2) 1980–1998 165 (40.5)
10.7 16.7 24.5
<0.001 <0.001 <0.001
2.1 (1.8–2.4) 1.6 (1.4–2.0) 1.9 (1.5–2.3)
Cesarean section 1967–1974 128 (8.5) 1975–1979 86 (14.7) 1980–1998 115 (28.3) 21 (26.6) Elective b Emergency b 13 (16.5)
2.4 6.1 11.8 4.7 7.9
<0.001 <0.001 <0.001 <0.001 0.06
3.3 (2.7–3.9) 2.3 (1.8–2.9) 2.4 (1.9–3.0) 5.2 (3.1–8.6) 1.8 (1.0–3.2)
Forceps 1967–1974 1975–1979 1980–1998
1.9 2.7 3.2
0.02 0.9 0.9
1.4 (1.1–1.9) 1.0 (0.6–1.6) 1.0 (0.6–1.7)
Procedure
Polio n (%)
50 (3.3) 16 (2.7) 13 (3.2)
Outcome
Polio n (%) Reference % p value a OR a (CI)
Birth weight <2500 g Gestational age <37 weeks Apgar score <7 at 1 min b Apgar score <7 at 5 min b Asphyxia c Transfer to pediatric ward Perinatal death Stillbirth, total Stillbirth, ≥28 weeks/1000 g Stillbirth, <28 weeks/1000 g
172 (6.9) 173 (7.2)
5.2 6.5
0.001 0.08
1.3 (1.1–1.5) 1.1 (1.0–1.3)
26 (4.5)
4.5
0.8
1.0 (0.6–1.4)
10 (1.7)
1.3
0.4
1.3 (0.7–2.4)
193 (12.5) 62 (2.5)
11.1 1.6
0.07 <0.001
1.2 (1.0–1.3) 1.7 (1.3–2.2)
52 (2.1) 40 (1.6) 26 (1.1)
1.1 1.1 0.7
0.05 0.3 0.5
1.3 (1.0–1.7) 1.2 (0.9–1.6) 1.1 (0.8–1.7)
14 (58.3)
58.3
1.0
1.0 (0.4–2.2)
a
Vacuum 1967–1974 1975–1979 1980–1998
54 (3.6) 22 (3.8) 18 (4.4)
1.9 3.6 4.5
0.003 0.9 0.8
1.5 (1.2–2.0) 1.0 (0.7–1.6) 0.9 (0.6–1.5)
a All p values and Odds Ratios (OR) with 95% Confidence Interval (CI) are adjusted for birth order and maternal age. b Data from 1989 and onwards, polio group n = 79, reference group n = 605 679.
All p values and Odds Ratios (OR) with 95% Confidence Interval (CI) are adjusted for time period, maternal age and birth order. b From 1978 and onwards. c From 1972 and onwards.
3.5. Birth outcome and neonatal complications
emergency sections in the polio group (Table 2). However, both emergency and elective rates were much higher in the polio than in the reference group. A higher proportion of cesarean sections in the polio group vs. the reference group was seen in pregnancies with pre-eclampsia (p = 0.004, OR = 2.0, CI = 1.2–3.2), low birth weight infants (p = 0.001, OR = 1.9, CI = 1.3–2.8), low gestational age infants (p = 0.005, OR = 1.8, CI = 1.2–2.7), and stillbirths (p = 0.02, OR = 3.0, CI = 1.2–7.6). The frequency of delivery by vacuum or forceps was higher for the polio group in the time period 1967–1974 (Table 2), when the overall cesarean section frequency was much lower.
Mean birth weight was 3383 g in the polio group vs. 3483 g in the reference group (p < 0.001). This difference persisted throughout the recording period. The polio group also had a higher frequency of low birth weight infants (Table 3). Mean gestational age was the same; 39.6 weeks and 39.7 weeks, respectively. Amongst infants with low birth weight, the proportion born at term (≥ 37 weeks) was also similar between the groups. The perinatal mortality was higher in the polio group (Table 3). In both groups the perinatal mortality declined during the recording period (Fig. 2). A higher perinatal mortality was found in pregnancies with pre-eclampsia vs. other pregnancies, in both the polio (8.2% vs. 1.9%, p = 0.001, OR = 4.6, CI = 1.9–10.9) and reference group (2.8% vs. 1.1%, p < 0.001, OR = 2.6, CI = 2.5–2.8). The frequency of birth defects was similar; 3.1% in the polio vs. 2.8% in the reference group.
Fig. 1. Cesarean sections 1967–1998.
Fig. 2. Perinatal mortality 1967–1998.
G. Veiby et al. / Journal of the Neurological Sciences 258 (2007) 27–32 Table 4 Maternal pre-pregnancy risk factors Risk factor
Polio n (%) Reference (%) p value a OR a (CI)
Arterial 2 (0.1) hypertension Diabetes 3 (0.1) Chronic cardiac 3 (0.1) disease Rheumatic disease 9 (0.4) Chronic kidney 34 (1.4) disease Kidney/ureter stone 13 (0.5)
0.2
0.4
0.5 (0.1–2.1)
0.3 0.1
0.2 0.7
0.5 (0.2–1.6) 1.3 (0.4–4.0)
0.3 0.9
0.1 0.001
1.7 (0.9–3.2) 1.8 (1.2–2.5)
0.2
<0.001
2.1 (1.6–4.7)
a
All p values and Odds Ratios (OR) with 95% Confidence Interval (CI) are adjusted for time period, maternal age and birth order.
3.6. Potential risk factors prior to pregnancy The occurrence of pre-pregnancy chronic kidney disease was increased in the polio group (Table 4). In addition to more pre-eclampsia, women with chronic kidney disease experienced a higher risk for preterm (< 37 weeks) infants in both the polio (15.2% vs. 7.1%, p = 0.03, OR = 3.1, CI = 1.1– 8.2) and the reference group (8.3% vs. 6.4%, p < 0.001, OR = 1.3, CI = 1.2–1.4). Excluding mothers with renal disease did not change the difference between the polio and reference group regarding major outcomes (preeclampsia, low birth weight, low gestational age, stillbirth, perinatal death). 4. Discussion The infants in the polio group more often had low birth weight, and perinatal death occurred more frequently. Low birth weight is a main risk factor for infant morbidity and mortality, usually related to reduced placental function in maternal systemic disease [9,16]. Pulmonary chronic hypoxemia in survivors of polio is a well recognized complication. Our results also indicate that renal disease and pre-eclampsia are risk factors associated with adverse pregnancy outcome after polio. The higher proportion of cesarean section in the polio group was probably due to mechanical obstruction during labor. Bony deformities in the pelvis and spine [17,18], and paralyzed muscles responsible for expulsive efforts during 2nd stage of labor [19], can lead to operative delivery in polio patients. The cases of uterine rupture in the polio group emphasize the necessity of active intervention when anatomical abnormalities are suspected. In addition, our results indicate that pregnancy-induced complications, affecting maternal and fetal health, contributed to the need for operative delivery in the polio group. The increased rate also of emergency sections shows that the need for operative intervention was underestimated in these patients. An important characteristic of the polio group was the higher frequency of renal and urinary tract disease. Kidney stone and chronic kidney disease were more common prior to pregnancy, and urinary tract infection more often
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complicated pregnancy. This is in line with previous studies on polio [20–22], and also for paraplegia in general [17,23]. Gestational proteinuria indicates renal damage, occurring before or during pregnancy [24]. Renal and urinary tract disease are risk factors for adverse perinatal outcome [9], and also for developing pre-eclampsia [15]. Similar to preeclampsia, renal dysfunction may present with high blood pressure, proteinuria, and edema. A clinical distinction between pre-eclampsia and renal disease is difficult, especially if the latter is precipitated during pregnancy [25]. Pre-eclampsia was significantly more frequent in the polio group, irrespective of maternal age and parity. This was still true when patients with renal disease were excluded. Pre-eclampsia has not previously been associated with polio or paraplegia [19,26]. However, polio seems to be an independent risk factor for pre-eclampsia, although we cannot completely exclude that symptoms related to renal/ urinary tract disease in the polio group were interpreted as pre-eclampsia. Interestingly, an association between preeclampsia and later renal disease has recently been reported [27]. The conception of pre-eclampsia has shifted from hypertension as the primary causal mechanism to the appreciation of pre-eclampsia as a syndrome involving several organ systems [28]. The higher rate of both renal disease and pre-eclampsia in the polio group could represent the same underlying pathophysiology in these patients. An alternative causal model for pre-eclampsia is immune maladaptation [15]. Immunological mechanisms have been suggested as significant for the post polio syndrome with progressive pareses [29–31]. However, an association to the outcome for our polio group would be speculative. Vaginal bleeding during pregnancy was increased in the polio group. Such bleeding is associated with adverse perinatal outcome [32–34]. The polio-related causes could not be identified in this registry-based study. Deliveries were also more often induced in the polio group, possibly due to more pregnancy complications and the presumption of a complicated delivery [35,36]. This registry-based study has the strength of including all births in Norway over a period of 30 years [37]. Although diagnostic validity and incomplete ascertainment is a concern in large-scale epidemiological studies, earlier reports on the MBRN demonstrate high sensitivity and correctness regarding the diagnosis of maternal disease [38]. Even though mild cases of polio may have been disregarded, it is most likely that clinically relevant polio was notified in the registry, as are other medically important maternal conditions [38]. During the last polio epidemics in Norway (1950–1954), 4158 acute paralytic cases were registered [39], presumably half females. The identification of 1758 polio survivors giving birth during our recording period indicates a reasonably high sensitivity. Although outcome variables were selected a priori, we cannot reject a possible effect of multiple testing on the results, nor have we accounted for outcome dependency of repeated births in the same female. Life style factors (e.g.
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smoking) and residual confounding may also have influenced the results. However, most differences showed such a high significance that these factors cannot explain our reported risks and complications. In conclusion, female survivors of polio have an elevated risk for pregnancy complications, operative delivery and adverse perinatal outcome. Operative delivery is often needed in these women, and attentiveness towards renal disease, urinary tract infection, pre-eclampsia and fetal growth restriction is of special importance. Polio survivors in childbearing age should be informed accordingly. This is a challenge in countries where polio infections have occurred frequently during the last three decades. Acknowledgements This study has been supported by the University of Bergen, Norway, and the Medical Birth Registry of Norway. References [1] Paccaud MF. World trends in poliomyelitis morbidity and mortality, 1951–1975. World Health Stat Q 1979;32(3):198–224. [2] Debré R, Thieffry S. Symptomatology and diagnosis of poliomyelitis. Monogr Ser World Health Organ 1955;26:109–36. [3] Melnick JL. Current status of poliovirus infections. Clin Microbiol Rev 1996;9(3):293–300. [4] Lobben B. The history of poliomyelitis in Norway — disease, society and patients. Tidsskr Nor Laegeforen 2001;121(30):3574–7. [5] World Health Organization. Polio Case Count. 13-10-2006. Ref Type: Generic. [6] Hull HF, Aylward RB. Progress towards global polio eradication. Vaccine 2001;19(31):4378–84. [7] Pallansch MA, Sandhu HS. The eradication of polio—progress and challenges. N Engl J Med 2006;355(24):2508–11. [8] Robertson SE, Chan C, Kim-Farley R, Ward N. Worldwide status of poliomyelitis in 1986, 1987 and 1988, and plans for its global eradication by the year 2000. World Health Stat Q 1990;43(2):80–90. [9] Valero DB, Soriano T, Albaladejo R, Juarranz M, Calle ME, Martinez D, et al. Risk factors for low birth weight: a review. Eur J Obstet Gynecol Reprod Biol 2004;116(1):3–15. [10] Nielsen NM, Rostgaard K, Askgaard D, Skinhoj P, Aaby P. Life-long morbidity among Danes with poliomyelitis. Arch Phys Med Rehabil 2004;85(3):385–91. [11] Vollset SE, Hirji KF. A microcomputer program for exact and asymptotic analysis of several 2 × 2 tables. Epidemiology 1991;2 (3):217–20. [12] Kolas T, Hofoss D, Daltveit AK, Nilsen ST, Henriksen T, Hager R, et al. Indications for cesarean deliveries in Norway. Am J Obstet Gynecol 2003;188(4):864–70. [13] Mayor S. Caesarean section rate in England reaches 22%. BMJ 2002;324(7346):1118. [14] Borthen I, Lossius P, Skjaerven R, Bergsjo P. Changes in frequency and indications for cesarean section in Norway 1967–1984. Acta Obstet Gynecol Scand 1989;68(7):589–93. [15] Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365 (9461):785–99. [16] Bernstein PS, Divon MY. Etiologies of fetal growth restriction. Clin Obstet Gynecol 1997;40(4):723–9.
[17] Robertson DN, Guttmann L. The paraplegic patient in pregnancy and labour. Proc R Soc Med 1963;56:381–7. [18] Greenspoon JS, Paul RH. Paraplegia and quadriplegia: special considerations during pregnancy and labor and delivery. Am J Obstet Gynecol 1986;155(4):738–41. [19] Baker ER, Cardenas DD. Pregnancy in spinal cord injured women. Arch Phys Med Rehabil 1996;77(5):501–7. [20] Editorial: renal calculi and poliomyelitis. Br Med J 1974;1(897):46–7. [21] Creevy CD, Tichy FY. Etiology and treatment of urinary lithiasis in severe poliomyelitis. AMA Arch Neurol Psychiatry 1952;68 (4):539–48. [22] Ellwood PM, Ratelle AE, Rodgers RS. Urological complications of poliomyelitis. J Urol 1956;76(4):447–52. [23] Chen Y, DeVivo MJ, Stover SL, Lloyd LK. Recurrent kidney stone: a 25-year follow-up study in persons with spinal cord injury. Urology 2002;60(2):228–32. [24] Eknoyan G, Hostetter T, Bakris GL, Hebert L, Levey AS, Parving HH, et al. Proteinuria and other markers of chronic kidney disease: a position statement of the National Kidney Foundation (NKF) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Am J Kidney Dis 2003;42(4):617–22. [25] Murakami S, Saitoh M, Kubo T, Koyama T, Kobayashi M. Renal disease in women with severe preeclampsia or gestational proteinuria. Obstet Gynecol 2000;96(6):945–9. [26] Young BK. Pregnancy in women with paraplegia. Adv Neurol 1994; 64:209–14. [27] Vikse BE, Irgens LM, Bostad L, Iversen BM. Adverse perinatal outcome and later kidney biopsy in the mother. J Am Soc Nephrol 2006;17(3):837–45. [28] Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension 2005;46(6):1243–9. [29] Dalakas MC. Pro-inflammatory cytokines and motor neuron dysfunction: is there a connection in post-polio syndrome? J Neurol Sci 2002;205(1):5–8. [30] Farbu E, Rekand T, Vik-Mo E, Lygren H, Gilhus NE, Aarli JA. Postpolio syndrome patients treated with intravenous immunoglobulin: a double-blinded randomized controlled pilot study. Eur J Neurol 2007;14(1):60–5. [31] Gonzalez H, Khademi M, Andersson M, Wallstrom E, Borg K, Olsson T. Prior poliomyelitis-evidence of cytokine production in the central nervous system. J Neurol Sci 2002;205(1):9–13. [32] Batzofin JH, Fielding WL, Friedman EA. Effect of vaginal bleeding in early pregnancy on outcome. Obstet Gynecol 1984;63(4):515–8. [33] Sipila P, Hartikainen-Sorri AL, Oja H, Von Wendt L. Perinatal outcome of pregnancies complicated by vaginal bleeding. Br J Obstet Gynaecol 1992;99(12):959–63. [34] Yang J, Savitz DA, Dole N, Hartmann KE, Herring AH, Olshan AF, et al. Predictors of vaginal bleeding during the first two trimesters of pregnancy. Paediatr Perinat Epidemiol 2005;19(4):276–83. [35] Macdorman MF, Mathews TJ, Martin JA, Malloy MH. Trends and characteristics of induced labour in the United States, 1989–98. Paediatr Perinat Epidemiol 2002;16(3):263–73. [36] Nassar AH, Adra AM, Chakhtoura N, Gomez-Marin O, Beydoun S. Severe preeclampsia remote from term: labor induction or elective cesarean delivery? Am J Obstet Gynecol 1998;179(5):1210–3. [37] Irgens LM. Medical birth registry—an essential resource in perinatal medical research. Tidsskr Nor Laegeforen 2002;122(26):2546–9. [38] Skomsvoll J, Ostensen M, Baste V, Irgens L. Validity of a rheumatic disease diagnosis in the Medical Birth Registry of Norway. Acta Obstet Gynecol Scand 2002;81(9):831–4. [39] Rekand T, Korv J, Farbu E, Roose M, Gilhus NE, Langeland N, et al. Long term outcome after poliomyelitis in different health and social conditions. J Epidemiol Community Health 2003;57(5):368–72.
Pregnancy, delivery and perinatal outcome in female survivors of polio Gyri Veiby a,c,⁎, Anne Kjersti Daltveit b,d , Nils Erik Gilhus a,c a
b
Department of Clinical Medicine, Section for Neurology, University of Bergen, Norway Department of Public Health and Primary Health Care, Section for Epidemiology and Medical Statistics, University of Bergen, Norway c Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway d Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway Received 3 July 2006; received in revised form 5 February 2007; accepted 12 February 2007 Available online 29 March 2007
Abstract Objective: To investigate possible effects on pregnancy, delivery and perinatal outcome in female survivors of polio. Methods: In a cohort design, data from the national population based Medical Birth Registry of Norway (MBRN) were used to compare all 2495 births recorded 1967–1998 by female survivors of polio with all 1.9 mill non-polio deliveries. The results were adjusted for time period, maternal age, and birth order by unconditional logistic regression, with effects presented as adjusted Odds Ratios (OR) with a corresponding 95% Confidence Interval (CI) and p values. Results: Female polio survivors had a higher occurrence of pre-eclampsia (3.4% vs. 2.8%, p = 0.003, OR = 1.4, CI = 1.1–1.7), gestational proteinuria (1.3% vs. 0.5%, p < 0.001, OR = 2.0, CI = 1.4–2.8), renal disease prior to pregnancy (1.4% vs. 0.9%, p = 0.001, OR = 1.8, CI = 1.2– 2.5), vaginal bleeding (3.8% vs. 2.0%, p < 0.001, OR = 1.7, CI = 1.4–2.1), and urinary tract infection during pregnancy (3.5% vs. 2.4%, p < 0.001, OR = 1.7, CI = 1.4–2.1). Deliveries complicated by obstruction of the birth process were more common in the polio group (6.1% vs. 2.0%, p < 0.001, OR = 4.8, CI = 4.0–5.6), and cesarean section was performed at a higher rate throughout the time period (13.2% vs. 8.3%, p < 0.001, OR = 2.7, CI = 2.4–3.1). Infants of polio mothers had a lower mean birth weight (3383 g vs. 3483 g, p < 0.001), and more often had a birth weight below 2500 g (6.9% vs. 5.2%, p = 0.001, OR = 1.3, CI = 1.1–1.5). There was no difference regarding pregnancy length. The risk of perinatal death was increased (2.1% vs. 1.1%, p = 0.05, OR = 1.3, CI = 1.0–1.7). Conclusion: Pregnancy in female survivors of polio is associated with an increased risk for complications during pregnancy and delivery, as well as an adverse perinatal outcome. Awareness towards risk factors should improve pre-natal care and possibly prevent complications. © 2007 Elsevier B.V. All rights reserved. Keywords: Polio; Pregnancy; Delivery; Cesarean section; Pre-eclampsia; Perinatal outcome
1. Introduction Patients with former polio experience difficulties later in life due to sequels after the acute illness. Complications during pregnancy and birth can be related to long-term effects of polio. The polio virus spreads through the orofecal route, and can infect the anterior horn motor neurons of the spinal cord producing an acute flaccid paralysis [1,2]. Muscle weakness ⁎ Corresponding author. Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway. Tel.: +47 55 97 50 00. E-mail address: [email protected] (G. Veiby). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.02.019
occur in 1–2% of infected persons during the acute illness [3], and is followed by a post-paralytic phase. Nearly 50% of those with acute muscle weakness develop post-paralytic permanent loss of motor function [2,4], affecting limbs, truncal and respiratory muscles. The lower limbs are most frequently affected. Global polio surveillance is incomplete, but has improved over the years. A total of 10 872 cases of confirmed paralytic polio has been reported since the year 2000 [5]. Vaccination programs have eradicated the large epidemics, but still there are outbreaks of paralytic polio in countries and areas where vaccination is insufficient [6,7]. Estimation of global polio incidence during the 1980's indicated 200,000–250,000
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annual cases of paralytic polio [8]. The majority acquired polio in early life. Thus, there is a considerable amount worldwide of women in childbearing age with polio related disability. In Norway, epidemics occurred during the 20th century until the vaccine was introduced in 1954. An estimate of 5000–10,000 persons are still living with poliorelated disability in Norway [4]. The aim of this study was to explore if female survivors of polio experience more complications during pregnancy and birth, and how such complications correlate to pregnancy risk factors. These obstetric risks should be known by public health officials in areas of the world where polio outbreaks have occurred during the last three decades. However, this information is difficult to obtain in poor countries with an inadequate infrastructure or ongoing political conflict. The national birth registry of Norway represents a unique tool to identify and examine a cohort of polio survivors during pregnancy. 2. Materials and methods 2.1. Patient selection Patients were identified through the Medical Birth Registry of Norway (MBRN), a national registry established in 1967, based on the compulsory notification of all births at 16 or more weeks of gestation. The registry contains medical data on the mother's health before and during pregnancy, on delivery, and on the newborn. A standardized notification form is filled in by the patient's attending physician and midwife, and sent within 9 days after discharge from the hospital. Diagnoses recorded before discharge from the birth institution are noted, and the text in the notification form is coded at MBRN partly according to the International Classification of Diseases, 8th Revision (ICD-8), and partly according to a coding system developed for the registry. MBRN is placed under the Norwegian Institute of Public Health. Complete ascertainment of all births is ensured through a record linkage to the National Population Registry, based on the unique identification number of all inhabitants of Norway. Our study included all deliveries registered between January 1, 1967 and December 31, 1998. An unchanged notification form was used during this period of time. As the last significant epidemic outbreaks of polio in Norway took place in 1950–1954, we chose not to include births after 1998. Inclusion criteria were defined as all deliveries by women diagnosed with previous polio according to ICD-8 criteria. The polio group consisted of 2495 births by 1758 women. In the majority, the polio-related disability was not further characterized. The reference group consisted of all 1.9 mill deliveries by women without a registered diagnosis of polio. Within the polio group, 60% of deliveries occurred in 1967–1974, 23% in 1975–1979, and 16% in 1980–1998. The corresponding distribution of non-polio births was 28%, 14%, and 58%.
2.2. Variables The selected variables have been defined by MBRN after consensus among obstetricians, neonatologists and epidemiologists. Demographic variables included age of mother in completed years, the infant's birth order, and type of obstetric institution. Risk factors associated with adverse pregnancy outcome were selected [9,10]: Hypertension, diabetes mellitus, chronic cardiac disease, rheumatic disease, and chronic kidney disease. Outcome measures for pregnancy, obstetrical complications, and the newborn were also selected a priori. Pregnancy complications included: Diabetes mellitus, urinary tract infection, pre-eclampsia, gestational proteinuria (proteinuria detected for the first time during pregnancy), pregnancyinduced hypertension (with/without edema), vaginal hemorrhage, and placental abruption. Pre-eclampsia was defined as proteinuria combined with pregnancy-induced hypertension or threatening eclampsia. Pregnancy-induced hypertension without proteinuria is not included in MBRN's current definition of pre-eclampsia. Obstetrical complications included: Induction of labor (augmentation of delivery not included), presentation anomalies, obstruction of birth process (mechanical obstruction of the fetus passing the birth canal), functional disturbance of birth process (atonia uteri, threatening uterine rupture, dystocia cervix uteri, prolonged labor, slow progression of 2nd stage, secondary delayed contractions, or rapid labor), uterine rupture, birth canal injuries, postpartum vaginal hemorrhage (> 500 ml), and intervention during birth (any intervention, cesarean section, forceps, or vacuum). The classification of cesarean sections into elective or emergency procedure was introduced in 1989. Perinatal outcome included: Gestational age in completed weeks, birth weight in grams, complicating neonatal conditions (birth weight < 2500 g, gestational age < 37 weeks, Apgar score < 7 at 1 min and 5 min, and asphyxia during delivery), transfer of the newborn to a pediatric ward, birth defects, and mortality (stillbirth, perinatal mortality). Birth defects were defined as severe or not severe according to a definition by MBRN based on ICD-8. Stillbirths consisted of all fetal deaths ≥ 16 weeks of gestation, occurring before or during birth. Perinatal mortality included all deaths occurring during the first 6 days in live born children ≥ 16 weeks of gestation, and all stillbirths ≥ 28 weeks of gestation (if unknown age of gestation: birth weight > 1000 g/birth length > 35 cm). 2.3. Statistics The analyses were based on crude, stratified and adjusted measures, and were performed by SPSS for Windows. Twosided p values < 0.05 were considered as statistical significant. Arithmetic mean was calculated for maternal age, birth order, gestational length, and birth weight, and analyzed by independent samples T tests to compare the polio and the
G. Veiby et al. / Journal of the Neurological Sciences 258 (2007) 27–32
reference group. Crosstabulated measures with expected cell count less than 5 were evaluated by exact tests based on paper by Vollset and Hirji [11]. All other variables were adjusted by unconditional logistic regression (potential confounding factors represented as categorical variables), and results are presented as adjusted Odds Ratios with corresponding 95% Confidence Intervals and p values. Period of time (1967–1974, 1975–1979, 1980–1998), maternal age (< 25, 25–29, 30–34, 35+ years) and birth order (first, second, third or more) were considered potential confounders or effect modifiers. We also included year of birth as a linear term in the model, but this had minimal impact on the outcomes, and is not included in the presented results. Effect modification was evaluated by Breslow–Days test. The periods of time were selected based on known polio-epidemics in Norway. Operative interventions during labor have changed during our recording period [12–14], and are presented separately for each time period. 3. Results
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Table 1 Pregnancy and obstetrical complications in the polio (n = 2495) and reference (n = 1,866 885) group Complication Hypertension, pregnancy-induced Pre-eclampsia Urinary tract infection during pregnancy Gestational proteinuria Vaginal bleeding during pregnancy Induction of delivery Presentation anomalies Obstruction of birth process Functional disturbance of birth process Rupture of the uterus b Birth canal injuries c Postpartum vaginal hemorrhage >500 ml
Polio n (%)
Reference p (%) value a 0.3
OR a (CI)
40 (1.6)
1.3
1.2 (0.9–1.6)
85 (3.4) 88 (3.5)
2.8 2.4
0.003 1.4 (1.1–1.7) <0.001 1.7 (1.4–2.1)
33 (1.3) 95 (3.8)
0.5 2.0
<0.001 2.0 (1.4–2.8) <0.001 1.7 (1.4–2.1)
441 (17.7) 13.4 121 (4.8) 4.7 152 (6.1) 2.0
<0.001 1.4 (1.2–1.5) 0.2 1.1 (0.9–1.4) <0.001 4.8 (4.0–5.6)
160 (6.4)
6.6
0.01
1.2 (1.0–1.5)
2 (0.1) 39 (1.8) 122 (4.9)
0.014 2.6 4.9
0.06 0.9 0.3
5.7 (0.9–19) 1.0 (0.7–1.3) 1.1 (0.9–1.3)
a
3.1. Demographic characteristics The mean maternal age in the polio group was 28.0 vs. 26.8 years in the reference group (p < 0.001). As the mean age and birth order differed significantly between the groups; all comparisons have been adjusted for this difference. A higher percentage of women in the polio group gave birth at a university hospital (29.6% vs. 24.9%, p < 0.001).
All p values and Odds Ratios (OR) with 95% Confidence Interval (CI) are adjusted for time period, maternal age and birth order. b Expected cell count <5: p value and corresponding OR with 95% CI is calculated by 2-sided exact test. c Deliveries by cesarean section not included.
The groups were similar regarding pregnancy–diabetes, preterm rupture of amniotic membranes and placental abruption.
3.2. Pregnancy complications
3.3. Obstetrical complications
Pre-eclampsia, gestational proteinuria, and urinary tract infection during pregnancy was more common in the polio group (Table 1). Pregnancy-induced hypertension did not differ significantly between the groups. However, when pregnancy-induced hypertension with edema, gestational proteinuria and pre-eclampsia were all combined, the total occurrence was clearly increased in the polio group (5.3% vs. 3.6%, p < 0.001, OR = 1.5, CI = 1.3–1.8). As chronic kidney disease increases the risk for preeclampsia [15], a comparison was made between women with and without such disease. As expected, the renal patients demonstrated a higher rate of pre-eclampsia in both the polio (p = 0.04, OR = 3.7) and the reference group (p < 0.001, OR = 1.5). When women with renal disease were excluded from the material, pre-eclampsia was still more common in the polio group (3.3% vs. 2.8%, p = 0.006, OR = 1.4, CI = 1.1–1.7). Vaginal bleeding occurred at a higher rate in the polio group (Table 1), this difference being confined to the first (p < 0.001, OR = 1.8, CI = 1.4–2.4) and second trimester (p < 0.001, OR = 2.1, CI = 1.4–3.2). An exclusion of such pregnancies from the material did not change the major perinatal outcomes in the polio group (low birth weight, low gestational age, perinatal death).
Polio patients more often experienced deliveries complicated by obstruction of the birth process (Table 1), and this occurred in a much higher proportion of cesarean sections compared to the reference group (44% vs. 23%, p < 0.001, OR = 2.6, CI = 2.1–3.2). Two polio mothers experienced uterine rupture during delivery, both with stillborn outcome. The overall rate of presentation anomalies was similar in the two groups, but at maternal age > 34 years there was a difference, mainly due to breech presentations in the polio group (7.6%, n = 26 vs. 3.7%, p < 0.001, OR = 2.1, CI = 1.4– 3.2). The significant difference between the groups for functional disturbance of the birth process (Table 1) was confined to the first time period (5.9%, n = 88 vs. 3.6%, p = 0.003, OR = 1.4, CI = 1.1–1.7). 3.4. Obstetrical interventions A higher frequency of interventions during birth occurred in the polio compared to the reference group (Table 2). There was a marked difference for cesarean sections (13.2% vs. 8.3%, p < 0.001, OR = 2.7, CI = 2.4–3.1), and this difference increased throughout the period (Fig. 1). Data from 1989 and onwards showed a higher number of elective in proportion to
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Table 2 Interventions during birth in the polio and reference group
Table 3 Birth outcome and neonatal complications in the polio and reference group
Reference %
p value a
OR a (CI)
Any intervention 1967–1974 327 (21.8) 1975–1979 153 (26.2) 1980–1998 165 (40.5)
10.7 16.7 24.5
<0.001 <0.001 <0.001
2.1 (1.8–2.4) 1.6 (1.4–2.0) 1.9 (1.5–2.3)
Cesarean section 1967–1974 128 (8.5) 1975–1979 86 (14.7) 1980–1998 115 (28.3) 21 (26.6) Elective b Emergency b 13 (16.5)
2.4 6.1 11.8 4.7 7.9
<0.001 <0.001 <0.001 <0.001 0.06
3.3 (2.7–3.9) 2.3 (1.8–2.9) 2.4 (1.9–3.0) 5.2 (3.1–8.6) 1.8 (1.0–3.2)
Forceps 1967–1974 1975–1979 1980–1998
1.9 2.7 3.2
0.02 0.9 0.9
1.4 (1.1–1.9) 1.0 (0.6–1.6) 1.0 (0.6–1.7)
Procedure
Polio n (%)
50 (3.3) 16 (2.7) 13 (3.2)
Outcome
Polio n (%) Reference % p value a OR a (CI)
Birth weight <2500 g Gestational age <37 weeks Apgar score <7 at 1 min b Apgar score <7 at 5 min b Asphyxia c Transfer to pediatric ward Perinatal death Stillbirth, total Stillbirth, ≥28 weeks/1000 g Stillbirth, <28 weeks/1000 g
172 (6.9) 173 (7.2)
5.2 6.5
0.001 0.08
1.3 (1.1–1.5) 1.1 (1.0–1.3)
26 (4.5)
4.5
0.8
1.0 (0.6–1.4)
10 (1.7)
1.3
0.4
1.3 (0.7–2.4)
193 (12.5) 62 (2.5)
11.1 1.6
0.07 <0.001
1.2 (1.0–1.3) 1.7 (1.3–2.2)
52 (2.1) 40 (1.6) 26 (1.1)
1.1 1.1 0.7
0.05 0.3 0.5
1.3 (1.0–1.7) 1.2 (0.9–1.6) 1.1 (0.8–1.7)
14 (58.3)
58.3
1.0
1.0 (0.4–2.2)
a
Vacuum 1967–1974 1975–1979 1980–1998
54 (3.6) 22 (3.8) 18 (4.4)
1.9 3.6 4.5
0.003 0.9 0.8
1.5 (1.2–2.0) 1.0 (0.7–1.6) 0.9 (0.6–1.5)
a All p values and Odds Ratios (OR) with 95% Confidence Interval (CI) are adjusted for birth order and maternal age. b Data from 1989 and onwards, polio group n = 79, reference group n = 605 679.
All p values and Odds Ratios (OR) with 95% Confidence Interval (CI) are adjusted for time period, maternal age and birth order. b From 1978 and onwards. c From 1972 and onwards.
3.5. Birth outcome and neonatal complications
emergency sections in the polio group (Table 2). However, both emergency and elective rates were much higher in the polio than in the reference group. A higher proportion of cesarean sections in the polio group vs. the reference group was seen in pregnancies with pre-eclampsia (p = 0.004, OR = 2.0, CI = 1.2–3.2), low birth weight infants (p = 0.001, OR = 1.9, CI = 1.3–2.8), low gestational age infants (p = 0.005, OR = 1.8, CI = 1.2–2.7), and stillbirths (p = 0.02, OR = 3.0, CI = 1.2–7.6). The frequency of delivery by vacuum or forceps was higher for the polio group in the time period 1967–1974 (Table 2), when the overall cesarean section frequency was much lower.
Mean birth weight was 3383 g in the polio group vs. 3483 g in the reference group (p < 0.001). This difference persisted throughout the recording period. The polio group also had a higher frequency of low birth weight infants (Table 3). Mean gestational age was the same; 39.6 weeks and 39.7 weeks, respectively. Amongst infants with low birth weight, the proportion born at term (≥ 37 weeks) was also similar between the groups. The perinatal mortality was higher in the polio group (Table 3). In both groups the perinatal mortality declined during the recording period (Fig. 2). A higher perinatal mortality was found in pregnancies with pre-eclampsia vs. other pregnancies, in both the polio (8.2% vs. 1.9%, p = 0.001, OR = 4.6, CI = 1.9–10.9) and reference group (2.8% vs. 1.1%, p < 0.001, OR = 2.6, CI = 2.5–2.8). The frequency of birth defects was similar; 3.1% in the polio vs. 2.8% in the reference group.
Fig. 1. Cesarean sections 1967–1998.
Fig. 2. Perinatal mortality 1967–1998.
G. Veiby et al. / Journal of the Neurological Sciences 258 (2007) 27–32 Table 4 Maternal pre-pregnancy risk factors Risk factor
Polio n (%) Reference (%) p value a OR a (CI)
Arterial 2 (0.1) hypertension Diabetes 3 (0.1) Chronic cardiac 3 (0.1) disease Rheumatic disease 9 (0.4) Chronic kidney 34 (1.4) disease Kidney/ureter stone 13 (0.5)
0.2
0.4
0.5 (0.1–2.1)
0.3 0.1
0.2 0.7
0.5 (0.2–1.6) 1.3 (0.4–4.0)
0.3 0.9
0.1 0.001
1.7 (0.9–3.2) 1.8 (1.2–2.5)
0.2
<0.001
2.1 (1.6–4.7)
a
All p values and Odds Ratios (OR) with 95% Confidence Interval (CI) are adjusted for time period, maternal age and birth order.
3.6. Potential risk factors prior to pregnancy The occurrence of pre-pregnancy chronic kidney disease was increased in the polio group (Table 4). In addition to more pre-eclampsia, women with chronic kidney disease experienced a higher risk for preterm (< 37 weeks) infants in both the polio (15.2% vs. 7.1%, p = 0.03, OR = 3.1, CI = 1.1– 8.2) and the reference group (8.3% vs. 6.4%, p < 0.001, OR = 1.3, CI = 1.2–1.4). Excluding mothers with renal disease did not change the difference between the polio and reference group regarding major outcomes (preeclampsia, low birth weight, low gestational age, stillbirth, perinatal death). 4. Discussion The infants in the polio group more often had low birth weight, and perinatal death occurred more frequently. Low birth weight is a main risk factor for infant morbidity and mortality, usually related to reduced placental function in maternal systemic disease [9,16]. Pulmonary chronic hypoxemia in survivors of polio is a well recognized complication. Our results also indicate that renal disease and pre-eclampsia are risk factors associated with adverse pregnancy outcome after polio. The higher proportion of cesarean section in the polio group was probably due to mechanical obstruction during labor. Bony deformities in the pelvis and spine [17,18], and paralyzed muscles responsible for expulsive efforts during 2nd stage of labor [19], can lead to operative delivery in polio patients. The cases of uterine rupture in the polio group emphasize the necessity of active intervention when anatomical abnormalities are suspected. In addition, our results indicate that pregnancy-induced complications, affecting maternal and fetal health, contributed to the need for operative delivery in the polio group. The increased rate also of emergency sections shows that the need for operative intervention was underestimated in these patients. An important characteristic of the polio group was the higher frequency of renal and urinary tract disease. Kidney stone and chronic kidney disease were more common prior to pregnancy, and urinary tract infection more often
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complicated pregnancy. This is in line with previous studies on polio [20–22], and also for paraplegia in general [17,23]. Gestational proteinuria indicates renal damage, occurring before or during pregnancy [24]. Renal and urinary tract disease are risk factors for adverse perinatal outcome [9], and also for developing pre-eclampsia [15]. Similar to preeclampsia, renal dysfunction may present with high blood pressure, proteinuria, and edema. A clinical distinction between pre-eclampsia and renal disease is difficult, especially if the latter is precipitated during pregnancy [25]. Pre-eclampsia was significantly more frequent in the polio group, irrespective of maternal age and parity. This was still true when patients with renal disease were excluded. Pre-eclampsia has not previously been associated with polio or paraplegia [19,26]. However, polio seems to be an independent risk factor for pre-eclampsia, although we cannot completely exclude that symptoms related to renal/ urinary tract disease in the polio group were interpreted as pre-eclampsia. Interestingly, an association between preeclampsia and later renal disease has recently been reported [27]. The conception of pre-eclampsia has shifted from hypertension as the primary causal mechanism to the appreciation of pre-eclampsia as a syndrome involving several organ systems [28]. The higher rate of both renal disease and pre-eclampsia in the polio group could represent the same underlying pathophysiology in these patients. An alternative causal model for pre-eclampsia is immune maladaptation [15]. Immunological mechanisms have been suggested as significant for the post polio syndrome with progressive pareses [29–31]. However, an association to the outcome for our polio group would be speculative. Vaginal bleeding during pregnancy was increased in the polio group. Such bleeding is associated with adverse perinatal outcome [32–34]. The polio-related causes could not be identified in this registry-based study. Deliveries were also more often induced in the polio group, possibly due to more pregnancy complications and the presumption of a complicated delivery [35,36]. This registry-based study has the strength of including all births in Norway over a period of 30 years [37]. Although diagnostic validity and incomplete ascertainment is a concern in large-scale epidemiological studies, earlier reports on the MBRN demonstrate high sensitivity and correctness regarding the diagnosis of maternal disease [38]. Even though mild cases of polio may have been disregarded, it is most likely that clinically relevant polio was notified in the registry, as are other medically important maternal conditions [38]. During the last polio epidemics in Norway (1950–1954), 4158 acute paralytic cases were registered [39], presumably half females. The identification of 1758 polio survivors giving birth during our recording period indicates a reasonably high sensitivity. Although outcome variables were selected a priori, we cannot reject a possible effect of multiple testing on the results, nor have we accounted for outcome dependency of repeated births in the same female. Life style factors (e.g.
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smoking) and residual confounding may also have influenced the results. However, most differences showed such a high significance that these factors cannot explain our reported risks and complications. In conclusion, female survivors of polio have an elevated risk for pregnancy complications, operative delivery and adverse perinatal outcome. Operative delivery is often needed in these women, and attentiveness towards renal disease, urinary tract infection, pre-eclampsia and fetal growth restriction is of special importance. Polio survivors in childbearing age should be informed accordingly. This is a challenge in countries where polio infections have occurred frequently during the last three decades. Acknowledgements This study has been supported by the University of Bergen, Norway, and the Medical Birth Registry of Norway. References [1] Paccaud MF. World trends in poliomyelitis morbidity and mortality, 1951–1975. World Health Stat Q 1979;32(3):198–224. [2] Debré R, Thieffry S. Symptomatology and diagnosis of poliomyelitis. Monogr Ser World Health Organ 1955;26:109–36. [3] Melnick JL. Current status of poliovirus infections. Clin Microbiol Rev 1996;9(3):293–300. [4] Lobben B. The history of poliomyelitis in Norway — disease, society and patients. Tidsskr Nor Laegeforen 2001;121(30):3574–7. [5] World Health Organization. Polio Case Count. 13-10-2006. Ref Type: Generic. [6] Hull HF, Aylward RB. Progress towards global polio eradication. Vaccine 2001;19(31):4378–84. [7] Pallansch MA, Sandhu HS. The eradication of polio—progress and challenges. N Engl J Med 2006;355(24):2508–11. [8] Robertson SE, Chan C, Kim-Farley R, Ward N. Worldwide status of poliomyelitis in 1986, 1987 and 1988, and plans for its global eradication by the year 2000. World Health Stat Q 1990;43(2):80–90. [9] Valero DB, Soriano T, Albaladejo R, Juarranz M, Calle ME, Martinez D, et al. Risk factors for low birth weight: a review. Eur J Obstet Gynecol Reprod Biol 2004;116(1):3–15. [10] Nielsen NM, Rostgaard K, Askgaard D, Skinhoj P, Aaby P. Life-long morbidity among Danes with poliomyelitis. Arch Phys Med Rehabil 2004;85(3):385–91. [11] Vollset SE, Hirji KF. A microcomputer program for exact and asymptotic analysis of several 2 × 2 tables. Epidemiology 1991;2 (3):217–20. [12] Kolas T, Hofoss D, Daltveit AK, Nilsen ST, Henriksen T, Hager R, et al. Indications for cesarean deliveries in Norway. Am J Obstet Gynecol 2003;188(4):864–70. [13] Mayor S. Caesarean section rate in England reaches 22%. BMJ 2002;324(7346):1118. [14] Borthen I, Lossius P, Skjaerven R, Bergsjo P. Changes in frequency and indications for cesarean section in Norway 1967–1984. Acta Obstet Gynecol Scand 1989;68(7):589–93. [15] Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365 (9461):785–99. [16] Bernstein PS, Divon MY. Etiologies of fetal growth restriction. Clin Obstet Gynecol 1997;40(4):723–9.
[17] Robertson DN, Guttmann L. The paraplegic patient in pregnancy and labour. Proc R Soc Med 1963;56:381–7. [18] Greenspoon JS, Paul RH. Paraplegia and quadriplegia: special considerations during pregnancy and labor and delivery. Am J Obstet Gynecol 1986;155(4):738–41. [19] Baker ER, Cardenas DD. Pregnancy in spinal cord injured women. Arch Phys Med Rehabil 1996;77(5):501–7. [20] Editorial: renal calculi and poliomyelitis. Br Med J 1974;1(897):46–7. [21] Creevy CD, Tichy FY. Etiology and treatment of urinary lithiasis in severe poliomyelitis. AMA Arch Neurol Psychiatry 1952;68 (4):539–48. [22] Ellwood PM, Ratelle AE, Rodgers RS. Urological complications of poliomyelitis. J Urol 1956;76(4):447–52. [23] Chen Y, DeVivo MJ, Stover SL, Lloyd LK. Recurrent kidney stone: a 25-year follow-up study in persons with spinal cord injury. Urology 2002;60(2):228–32. [24] Eknoyan G, Hostetter T, Bakris GL, Hebert L, Levey AS, Parving HH, et al. Proteinuria and other markers of chronic kidney disease: a position statement of the National Kidney Foundation (NKF) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Am J Kidney Dis 2003;42(4):617–22. [25] Murakami S, Saitoh M, Kubo T, Koyama T, Kobayashi M. Renal disease in women with severe preeclampsia or gestational proteinuria. Obstet Gynecol 2000;96(6):945–9. [26] Young BK. Pregnancy in women with paraplegia. Adv Neurol 1994; 64:209–14. [27] Vikse BE, Irgens LM, Bostad L, Iversen BM. Adverse perinatal outcome and later kidney biopsy in the mother. J Am Soc Nephrol 2006;17(3):837–45. [28] Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension 2005;46(6):1243–9. [29] Dalakas MC. Pro-inflammatory cytokines and motor neuron dysfunction: is there a connection in post-polio syndrome? J Neurol Sci 2002;205(1):5–8. [30] Farbu E, Rekand T, Vik-Mo E, Lygren H, Gilhus NE, Aarli JA. Postpolio syndrome patients treated with intravenous immunoglobulin: a double-blinded randomized controlled pilot study. Eur J Neurol 2007;14(1):60–5. [31] Gonzalez H, Khademi M, Andersson M, Wallstrom E, Borg K, Olsson T. Prior poliomyelitis-evidence of cytokine production in the central nervous system. J Neurol Sci 2002;205(1):9–13. [32] Batzofin JH, Fielding WL, Friedman EA. Effect of vaginal bleeding in early pregnancy on outcome. Obstet Gynecol 1984;63(4):515–8. [33] Sipila P, Hartikainen-Sorri AL, Oja H, Von Wendt L. Perinatal outcome of pregnancies complicated by vaginal bleeding. Br J Obstet Gynaecol 1992;99(12):959–63. [34] Yang J, Savitz DA, Dole N, Hartmann KE, Herring AH, Olshan AF, et al. Predictors of vaginal bleeding during the first two trimesters of pregnancy. Paediatr Perinat Epidemiol 2005;19(4):276–83. [35] Macdorman MF, Mathews TJ, Martin JA, Malloy MH. Trends and characteristics of induced labour in the United States, 1989–98. Paediatr Perinat Epidemiol 2002;16(3):263–73. [36] Nassar AH, Adra AM, Chakhtoura N, Gomez-Marin O, Beydoun S. Severe preeclampsia remote from term: labor induction or elective cesarean delivery? Am J Obstet Gynecol 1998;179(5):1210–3. [37] Irgens LM. Medical birth registry—an essential resource in perinatal medical research. Tidsskr Nor Laegeforen 2002;122(26):2546–9. [38] Skomsvoll J, Ostensen M, Baste V, Irgens L. Validity of a rheumatic disease diagnosis in the Medical Birth Registry of Norway. Acta Obstet Gynecol Scand 2002;81(9):831–4. [39] Rekand T, Korv J, Farbu E, Roose M, Gilhus NE, Langeland N, et al. Long term outcome after poliomyelitis in different health and social conditions. J Epidemiol Community Health 2003;57(5):368–72.