Video Abstract

Video Abstract

BACKGROUND AND OBJECTIVES:

Long-term outcomes of urinary tract infection (UTI) in childhood are not well known. Pregnancy may reveal latent renal damage caused by a UTI because of stress on the kidneys.

METHODS:

Our cohort included adult women with an ultrasonography taken because of a childhood UTI in 1981–1991 (N = 1175). Nine women with a severe congenital kidney malformation or urinary tract obstruction were excluded. Altogether, 260 mothers with a childhood UTI and 500 population-based control mothers without a childhood UTI matched for age, and delivery dates were compared. Our primary end point was the proportion of women with essential or gestational hypertension, preeclampsia, proteinuria, or pyelonephritis during the first pregnancy.

RESULTS:

The pregnancy outcomes of the women with a UTI in childhood did not differ from those of the controls because 105 of 260 (40%) patients met the primary end point compared with 204 of 500 (41%) controls (relative risk [RR] 0.99; 95% confidence interval [CI] 0.82 to 1.2; P = .91). Similarly, there were no significant differences between the 2 groups in essential hypertension (RR 1.0; 95% CI 0.65 to 1.6; P = .92), gestational hypertension (RR 0.93; 95% CI 0.74 to 1.2; P = .54), preeclampsia (RR 1.5; 95% CI 0.91 to 2.5; P = .11), proteinuria (RR 1.2; 95% CI 0.81 to 1.8; P = .36) or pyelonephritis (2 controls and none of the patients; P = .55) during the first pregnancy.

CONCLUSIONS:

Childhood UTIs did not increase the risk of pregnancy-related complications in this controlled population-based study. Thus, UTIs in childhood without severe urinary tract abnormalities appear to have a minimal effect on kidney health in early adulthood.

What’s Known on This Subject:

The long-term outcome after a urinary tract infection (UTI) in childhood is not well documented. Pregnancy may reveal latent renal damage due to kidney stress. Only 1 small controlled study has been done earlier to evaluate the risk of pregnancy complications after a childhood UTI.

What This Study Adds:

In this controlled population-based study, childhood UTIs did not increase the risk of pregnancy-related complications in women. UTIs in children without severe urinary tract abnormalities appear to have a minimal effect on kidney health in early adulthood.

Urinary tract infection (UTI) is one of the most common pediatric bacterial infections,1  and it has been suggested that a UTI in childhood may cause kidney scarring and impaired renal function later in life.2,3  In the absence of severe urinary tract abnormalities, however, children with UTIs do not seem to be at risk for developing chronic kidney disease as adults.4,5 

Pregnancy is a period in a woman’s life that causes stress for the kidneys,6  and, although women with normal kidneys are usually able to make the renal adaptations required during pregnancy, abnormalities of the urinary tract or lack of renal functional reserve can be manifested for the first time during pregnancy. We hypothesized that renal damage after childhood UTIs could lead to a loss of kidney functional reserve, which may first manifest itself as an increased risk of pregnancy-related complications. To date, in only 1 comparative study, with a total of 41 women, has a risk of pregnancy-related complications after a childhood UTI been reported.7 

We set out to compare the pregnancy-related complications in adult women after UTIs in childhood with those of control women during the first pregnancy in a population-based cohort study to evaluate whether UTIs in children without severe urinary tract abnormalities affect kidney health in adulthood.

The plan for a population-based cohort study of the pregnancy outcomes in women with a UTI in childhood was approved by the Northern Ostrobothnia Hospital District, Oulu, Finland and the social and health services of the city of Oulu, Finland. We identified the initial cohort using a register of all children who had undergone a renal and urinary tract ultrasonography (RUS) examination because of a childhood UTI at the Department of Pediatric Radiology, Oulu University Hospital, Finland, during the years 1981–1991. We first excluded those who had had a severe urinary tract obstruction, congenitally malformed kidneys, or kidney dysplasia in the first ultrasonography in childhood and then identified from among the remainder a cohort of women who had given birth to ≥1 child. Data on a group of population-based control women without UTIs in childhood were retrieved from the general register of mothers from the city of Oulu giving birth at Oulu University Hospital, and ≥2 matched control women for each patient were selected on the basis of the following criteria: age at the birth of the first child (±6 months) and delivery date (same calendar year). Copies of the childhood hospital medical records, antenatal medical records of the women, and medical records of the infants of both the women with a UTI in childhood and control women were reviewed, and data, including original blood pressure measurements, were collected by the physicians in the research team using a standardized data entry sheet. During the process of reviewing the childhood hospital records of selected control women, we found 5 additional cases in women with a childhood UTI who had undergone a voiding cystourethrography (VCUG) and intravenous urography instead of an RUS. These were analyzed along with the previously determined cases.

All children with a first episode of a confirmed UTI at the Oulu University Hospital in the 1980s underwent imaging performed initially with an RUS and completed with a VCUG for children aged <2 years, in accordance with the recommendations at that time. Intravenous urography was also performed if decided on by the pediatric urologist treating the patient. The mild renal pelvis dilatation seen in RUS was defined by the clinical pediatric radiologist who performed the examination.

The public maternity clinic services in Finland are used by almost all pregnant women regardless of their socioeconomic status. At least 9 follow-up visits are recommended for primiparas and 8 for multiparas.8  At each antenatal appointment starting from 8 to 10 weeks’ gestation until delivery, weight and blood pressure are measured, and a dipstick urine analysis is performed as a routine screening test.

Our primary end point was the proportion of women with essential or gestational hypertension, preeclampsia, proteinuria, or pyelonephritis during the first pregnancy. Essential hypertension was defined as elevated blood pressure (systolic ≥140 mm Hg and/or diastolic of 90 mm Hg on ≥2 occasions) before 20 weeks’ gestation or the use of antihypertensive medication. Gestational hypertension referred to a new onset of hypertension (systolic ≥140 mm Hg and/or diastolic ≥90 mm Hg on 2 separate occasions >6 hours apart) after 20 weeks of pregnancy in a previously normotensive woman. Proteinuria was defined as a urine specimen with 1+ by dipstick on 2 occasions, random urine specimen with ≥2+ by dipstick, or urinary protein excretion ≥0.3 g in a 24-hour urine collection test. A diagnosis of preeclampsia was made in a previously normotensive woman who developed hypertension and proteinuria after 20 weeks’ gestation and superimposed preeclampsia in a woman with essential hypertension who developed proteinuria after 20 weeks’ gestation. The diagnostic criteria for pyelonephritis included pyuria (at least 1+ by dipstick), bacteriuria (growth of >100 000 colony forming units per mL), and a fever >38°C or C-reactive protein concentration >50 mg/L.

We calculated the sample size on the basis of the assumption that 10% of pregnant women without a history of childhood UTI meet the primary end point. The occurrence of the prespecified primary end point was based on a clinical estimate by the obstetricians in the research team before initiation of the study. We regarded it as clinically significant if women with UTIs in childhood had a twofold increase in their risk of reaching this end point. Given a type 1 error of 5%, we had to take ≥159 pregnant women with childhood UTIs and 2 population-based control women per case (ie, 318 control women). To compare the pregnancy outcomes in women with UTIs in childhood with those in women without childhood UTIs, relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The differences between the women with a childhood UTI and control women in the proportions of women with given outcomes were assessed with the standard normal deviate test. The sample size for the independent cohort study and the 95% CIs of the proportions and RRs were calculated by using the StatsDirect statistics software 3.1.9  The statistics were calculated by using StatsDirect9  and IBM SPSS Statistics version 25 (IBM SPSS Statistics, IBM Corporation). In all instances, 2-tailed P values <.05 were considered statistically significant.

Altogether, 1175 girls with a UTI in childhood were identified from the hospital records, and 342 (29%) of them had delivered their first child at the time of data retrieval (Fig 1). Of these 342 women, 9 who had a severe urinary tract abnormality in the first RUS were excluded: 5 with ureteropelvic junction obstruction or stenosis, 1 with vesicourethral stenosis, 1 with renal agenesis, 1 with renal dysplasia, and 1 with a unilateral shrunken kidney. Vesicoureteral reflux (VUR) or mild RUS abnormalities were not taken to be exclusion criteria. One pregnant woman with glomerulonephritis during pregnancy was excluded. Altogether, 72 women were excluded because they had incomplete medical records (53 with missing or incomplete antenatal records and 19 with missing data on childhood imaging). This left 260 mothers with a UTI in childhood for the analyses, for whom we had 500 control women matched for age and delivery date. Two control women were available for 93% of the women with a UTI in childhood. The mean age of the 260 mothers with a UTI in childhood was 24.2 (SD 3.9) years at first birth.

FIGURE 1

Study profile.

FIGURE 1

Study profile.

A total of 153 of 260 (59%) women with a childhood UTI had had recurrent UTIs in childhood, and 96 (37%) had received antibiotic prophylaxis for UTIs (Table 1). The mean number of UTI episodes per patient was 2.6 (SD 2.1). The first UTI was classified as pyelonephritis in 55% of women with a childhood UTI. RUS was abnormal in 47 of 255 (18%) women with a childhood UTI, the most frequent abnormal findings being mild renal pelvis dilatation in 16 (6.3%) women and duplex kidney in another 16 (6.3%). Unilateral renal scars were diagnosed in 10 (3.9%) patients. VCUGs were performed on 161 (62%) girls after a childhood UTI, with a grade ≥III VUR diagnosed in 23 of 161 (14%) patients, whereas the majority had no VUR (n = 90; 56%) or mild (grade I or II) VUR (n = 48; 30%). A total of 16 of 260 (6.2%) women had been operated on for VUR as children, 13 of 16 by open surgery, and 3 by endoscopic surgery. Altogether, 168 (65%) women had undergone intravenous urography in childhood, and the findings had been abnormal in 63 patients. Ureteral dilatation was detected in 38 of 168 (23%) cases, a duplex kidney in 18 and a unilateral renal scar in 14.

TABLE 1

Details of UTI and Imaging in Childhood in 260 Women Followed-up After Childhood UTI

n = 260
History of UTIs  
 ≥1 pyelonephritis during childhood,an (%) 130 (60) 
  First UTI febrilea 126 (55) 
 Recurrent UTIs in childhood, n (%) 153 (59) 
 No. UTIs, mean (SD) 2.6 (2.1) 
Previous treatments, n (%)  
 Antimicrobial prophylaxis 96 (37) 
 VUR treatment 16 (6.2) 
  Open surgery 13 (5.0) 
  Endoscopic therapy 3 (1.2) 
Imaging in childhood in 1980–1991  
 RUS findings n = 255 
  Abnormal RUS, n (%) 47 (18) 
   Mild renal pelvis dilatation 16 (6.3) 
   Ureteral dilatation 5 (2.0) 
   Scar, unilateral 10 (3.9) 
   Duplex kidney 16 (6.3) 
   Enlarged kidney, SD >2, unilateral 2 (0.8) 
   Small kidney, SD <−2, unilateral 3 (1.2) 
   Thickened or trabeculated bladder wall 8 (3.1) 
   Elevated residual volume 2 (0.8) 
   Other minor abnormality 8 (3.1) 
 VCUG n = 161 
  Abnormal first VCUG, n (%) 79 (49) 
   Any VUR 71 (44) 
   VUR grade I–II 48 (30) 
   VUR grade ≥III 23 (14) 
 Grade of VUR in the last VCUG n = 160 
  VUR grade I–II, n (%) 45 (28) 
  VUR grade ≥III, n (%) 0 (0) 
 Intravenous urography n = 168 
  Abnormal urography, n (%) 63 (38) 
   Mild renal pelvis dilatation 7 (4.2) 
   Ureteral dilatation 38 (23) 
   Scar 14 (8.3) 
   Duplex kidney 18 (11) 
   Other minor abnormality 9 (5.4) 
n = 260
History of UTIs  
 ≥1 pyelonephritis during childhood,an (%) 130 (60) 
  First UTI febrilea 126 (55) 
 Recurrent UTIs in childhood, n (%) 153 (59) 
 No. UTIs, mean (SD) 2.6 (2.1) 
Previous treatments, n (%)  
 Antimicrobial prophylaxis 96 (37) 
 VUR treatment 16 (6.2) 
  Open surgery 13 (5.0) 
  Endoscopic therapy 3 (1.2) 
Imaging in childhood in 1980–1991  
 RUS findings n = 255 
  Abnormal RUS, n (%) 47 (18) 
   Mild renal pelvis dilatation 16 (6.3) 
   Ureteral dilatation 5 (2.0) 
   Scar, unilateral 10 (3.9) 
   Duplex kidney 16 (6.3) 
   Enlarged kidney, SD >2, unilateral 2 (0.8) 
   Small kidney, SD <−2, unilateral 3 (1.2) 
   Thickened or trabeculated bladder wall 8 (3.1) 
   Elevated residual volume 2 (0.8) 
   Other minor abnormality 8 (3.1) 
 VCUG n = 161 
  Abnormal first VCUG, n (%) 79 (49) 
   Any VUR 71 (44) 
   VUR grade I–II 48 (30) 
   VUR grade ≥III 23 (14) 
 Grade of VUR in the last VCUG n = 160 
  VUR grade I–II, n (%) 45 (28) 
  VUR grade ≥III, n (%) 0 (0) 
 Intravenous urography n = 168 
  Abnormal urography, n (%) 63 (38) 
   Mild renal pelvis dilatation 7 (4.2) 
   Ureteral dilatation 38 (23) 
   Scar 14 (8.3) 
   Duplex kidney 18 (11) 
   Other minor abnormality 9 (5.4) 
a

Denominators vary because of missing data.

Preexisting diseases were comparable between the women with a childhood UTI and control women, but the women with childhood UTIs had more diagnosed autoimmune diseases than the control women (4.6% vs 1.8%) (Table 2). The mean BMI of both women with a childhood UTI and control women at the first antenatal visit had been 23 kg/m2 (SD 4.4 and 4.0, respectively). None of the women with a childhood UTI and 8 of 500 (1.6%) control women were severely obese (BMI >35 kg/m2). In total, 23% of the women with a childhood UTI and 21% of the control women reported having smoked before the first antenatal visit.

TABLE 2

Characteristics of the Women Who Had a Childhood UTI (n = 260) and the Control Women (n = 500) During Their First Pregnancy Child

Patients, n = 260Controls, n = 500
Women   
 Chronic diseases,an (%)   
  Epilepsy 4 (1.5) 10b (2) 
  Congenital heart disease 2 (0.8) 0 (0) 
  Any autoimmune disease 12 (4.6) 9 (1.8) 
   Hypothyroidism 7 (2.7) 4 (0.8) 
   Diabetes mellitus 2 (0.8) 2 (0.4) 
   Juvenile rheumatoid arthritis 2 (0.8) 1 (0.2) 
   Graves’ disease 1 (0.4) 0 (0) 
   Inflammatory bowel disease 0 (0) 1 (0.2) 
   Multiple sclerosis 0 (0) 1 (0.2) 
  Obesity (BMI >35) 0 (0) 8 (1.6) 
  Cancer 2 (0.8) 0 (0) 
  Benign kidney tumor 0 (0) 2 (0.4) 
  MEN1 1 (0.4) 0 (0) 
  Alcohol abuse 2 (0.8) 2 (0.4) 
  Drug abuse 2 (0.8) 0 (0) 
  Other heart disease 0 (0) 3 (0.6) 
  Other bowel disease 0 (0) 2 (0.4) 
  Other kidney disease 0 (0) 1 (0.2) 
 Wt at first antenatal visit, kg, mean (SD) 63 (13) 61 (11) 
 BMI at first antenatal visit, mean (SD) 23 (4.4) 23 (4.0) 
 Highest wt during pregnancy, kg, mean (SD) 79 (16) 77 (13) 
 Gestational diabetes, n (%) 23b (8.9) 36b (7.3) 
 Smoking during pregnancy, n (%) 54b (23) 104b (21) 
 Length of pregnancy, wk, mean (SD) 39 (1.9) 39 (1.6) 
 Mode of delivery, n (%)   
  Vaginal 171b (74) 376b (75) 
  Vacuum-assisted vaginal 24 (10) 45 (9.0) 
  Cesarean delivery 37 (16) 78 (16) 
Infants   
 Birth wt, g, mean (SD) 3429 (563) 3451 (499) 
 Apgar score, n (%)   
  1 min 8.5 (1.2) 8.6 (1.1) 
  5 min 8.9 (0.9) 8.9 (0.7) 
  10 min 9.2 (0.8) 9.2 (0.6) 
Patients, n = 260Controls, n = 500
Women   
 Chronic diseases,an (%)   
  Epilepsy 4 (1.5) 10b (2) 
  Congenital heart disease 2 (0.8) 0 (0) 
  Any autoimmune disease 12 (4.6) 9 (1.8) 
   Hypothyroidism 7 (2.7) 4 (0.8) 
   Diabetes mellitus 2 (0.8) 2 (0.4) 
   Juvenile rheumatoid arthritis 2 (0.8) 1 (0.2) 
   Graves’ disease 1 (0.4) 0 (0) 
   Inflammatory bowel disease 0 (0) 1 (0.2) 
   Multiple sclerosis 0 (0) 1 (0.2) 
  Obesity (BMI >35) 0 (0) 8 (1.6) 
  Cancer 2 (0.8) 0 (0) 
  Benign kidney tumor 0 (0) 2 (0.4) 
  MEN1 1 (0.4) 0 (0) 
  Alcohol abuse 2 (0.8) 2 (0.4) 
  Drug abuse 2 (0.8) 0 (0) 
  Other heart disease 0 (0) 3 (0.6) 
  Other bowel disease 0 (0) 2 (0.4) 
  Other kidney disease 0 (0) 1 (0.2) 
 Wt at first antenatal visit, kg, mean (SD) 63 (13) 61 (11) 
 BMI at first antenatal visit, mean (SD) 23 (4.4) 23 (4.0) 
 Highest wt during pregnancy, kg, mean (SD) 79 (16) 77 (13) 
 Gestational diabetes, n (%) 23b (8.9) 36b (7.3) 
 Smoking during pregnancy, n (%) 54b (23) 104b (21) 
 Length of pregnancy, wk, mean (SD) 39 (1.9) 39 (1.6) 
 Mode of delivery, n (%)   
  Vaginal 171b (74) 376b (75) 
  Vacuum-assisted vaginal 24 (10) 45 (9.0) 
  Cesarean delivery 37 (16) 78 (16) 
Infants   
 Birth wt, g, mean (SD) 3429 (563) 3451 (499) 
 Apgar score, n (%)   
  1 min 8.5 (1.2) 8.6 (1.1) 
  5 min 8.9 (0.9) 8.9 (0.7) 
  10 min 9.2 (0.8) 9.2 (0.6) 

MEN1, multiple endocrine neoplasia type 1.

a

Essential hypertension is reported as a secondary outcome.

b

Denominators vary because of missing data.

The pregnancy outcomes of women with a UTI in childhood did not differ from those of the control women because 105 of 260 (40%) women with a UTI in childhood met the primary outcome end point compared with 204 of 500 (41%) of the control women (RR 0.99; 95% CI 0.82 to 1.2; P = .91) (Table 3). Altogether, 25 (9.6%) women with a history of UTI and 47 (9.4%) control women had essential hypertension (RR 1.0; 95% CI 0.65 to 1.6; P = .92), whereas gestational hypertension was diagnosed in 75 (29%) women with a UTI in childhood and 155 (31%) control women (RR 0.93; 95% CI 0.74 to 1.2; P = .54). A total of 35 (13%) women with a childhood UTI and 56 (11%) women in the control group had proteinuria (RR 1.2; 95% CI 0.81 to 1.8; P = .36). Preeclampsia was diagnosed in 25 (9.6%) women with a UTI in childhood and 32 (6.4%) control women (RR 1.5; 95% CI 0.91 to 2.5; P = .11), and superimposed preeclampsia was diagnosed in 6 (2.3%) women with a UTI in childhood and 8 (1.6%) women in the control group (RR 1.4; 95% CI 0.53 to 3.9; P = .49), respectively. None of the women with a UTI in childhood (0%) had pyelonephritis during pregnancy, whereas 2 episodes of pyelonephritis occurred in women in the control group (0.4%; RR 0; 95% CI 0 to 3.7; P = .55). Altogether, 30 of 256 (12%) women with a childhood UTI and 41 (8.2%) control women had asymptomatic bacteriuria or cystitis during pregnancy (P = .12). Gestational diabetes was diagnosed in 8.9% of the women with a UTI in childhood and 7.3% of those in the control group (Table 2).

TABLE 3

Pregnancy Outcomes in the Women With UTIs in Childhood and the Control Women

Patients (n = 260), n (%)Controls (n = 500), n (%)RR95% CIP
Primary outcome: any pregnancy complicationa 105 (40) 204 (41) 0.99 0.82 to 1.2 .91 
Secondary outcomes      
 Essential hypertension 25 (9.6) 47 (9.4) 1.0 0.65 to 1.6 .92 
 Gestational hypertension 75 (29) 155 (31) 0.93 0.74 to 1.2 .54 
 Preeclampsia 25 (9.6) 32 (6.4) 1.5 0.91 to 2.5 .11 
 Superimposed preeclampsia 6 (2.3) 8 (1.6) 1.4 0.53 to 3.9 .49 
 Proteinuria 35 (13) 56 (11) 1.2 0.81 to 1.8 .36 
 Pyelonephritis 0 (0) 2 (0.4) b .55 
 Preterm birthc 14 (5.4) 19 (3.8) 1.4 0.73 to 2.7 .31 
 SGA infantd 12 (4.6) 14 (2.8) 1.6 0.79 to 3.4 .19 
Patients (n = 260), n (%)Controls (n = 500), n (%)RR95% CIP
Primary outcome: any pregnancy complicationa 105 (40) 204 (41) 0.99 0.82 to 1.2 .91 
Secondary outcomes      
 Essential hypertension 25 (9.6) 47 (9.4) 1.0 0.65 to 1.6 .92 
 Gestational hypertension 75 (29) 155 (31) 0.93 0.74 to 1.2 .54 
 Preeclampsia 25 (9.6) 32 (6.4) 1.5 0.91 to 2.5 .11 
 Superimposed preeclampsia 6 (2.3) 8 (1.6) 1.4 0.53 to 3.9 .49 
 Proteinuria 35 (13) 56 (11) 1.2 0.81 to 1.8 .36 
 Pyelonephritis 0 (0) 2 (0.4) b .55 
 Preterm birthc 14 (5.4) 19 (3.8) 1.4 0.73 to 2.7 .31 
 SGA infantd 12 (4.6) 14 (2.8) 1.6 0.79 to 3.4 .19 
a

Comprising essential or gestational hypertension, preeclampsia, proteinuria, or pyelonephritis during the first pregnancy.

b

Two controls and none of the patients.

c

Delivery before 37 wk of pregnancy.

d

Birth wt <10th percentile for gestational age.

Both the women with a UTI in childhood and the control women delivered at 39 weeks’ gestation on average (SD 1.9 and 1.6, respectively) (Table 1). There was no difference in the occurrence of preterm birth (delivery before 37 weeks of pregnancy) because 14 (5.4%) women with a childhood infection and 19 (3.8%) control women delivered preterm (RR 1.4; 95% CI 0.73 to 2.7; P = .31) (Table 3). The mean birth weights in the 2 groups (with and without maternal childhood UTI) were 3429 g (SD 563) and 3451 g (SD 499) (Table 1). A total of 12 (4.6%) children born to women with a UTI in childhood and 14 (2.8%) children born to control women were small for gestational age (SGA), which means a birth weight <10th percentile for the gestational age (RR 1.6; 95% CI 0.79 to 3.4; P = .19; Table 3). In a subgroup analysis, the pregnancy outcomes in the women with any grade of VUR did not differ from that of control women (Table 4). Similarly, there was no significant difference in the pregnancy outcomes between the women who had abnormal findings in a RUS and either the control women or those who had recurrent UTIs. Women with ≥1 case of pyelonephritis in childhood had more diagnosed cases of preeclampsia than the control women (16 of 130; 12% vs 15 of 248; 6.0%; P = .047), but there were no significant differences between the 2 groups for any other pregnancy outcomes.

TABLE 4

Subgroup Analysis of Pregnancy Outcomes According to VUR Results in Childhood in the Women Who Underwent VCUG (n = 161) and the Control Women

No VUR (n = 90), n (%)Gradus 1–2 VUR (n = 48), n (%)Gradus ≥3 VURa (n = 23), n (%)Controlsa (n = 304), n (%)Pb
Any pregnancy complicationc 29 (32) 21 (44) 9 (39) 124 (41) .46 
Essential hypertension 4 (4.4) 7 (15) 2 (8.7) 30 (9.9) .20 
Gestational hypertension 20 (22) 14 (29) 8 (35) 94 (31) .41 
Preeclampsia 3 (3.3) 5 (10) 2 (8.7) 17 (5.6) .28 
Superimposed preeclampsia 1 (1.1) 1 (2.1) 0 (0) 5 (1.6) .90 
Proteinuria 7 (7.8) 6 (13) 3 (13) 30 (9.9) .70 
Pyelonephritis 0 (0) 0 (0) 0 (0) 2 (0.66) .99 
Preterm birthd 4 (4.4) 2 (4.2) 0 (0) 12 (3.9) .92 
SGA infante 4 (4.4) 1 (2.1) 0 (0) 8 (2.6) .76 
No VUR (n = 90), n (%)Gradus 1–2 VUR (n = 48), n (%)Gradus ≥3 VURa (n = 23), n (%)Controlsa (n = 304), n (%)Pb
Any pregnancy complicationc 29 (32) 21 (44) 9 (39) 124 (41) .46 
Essential hypertension 4 (4.4) 7 (15) 2 (8.7) 30 (9.9) .20 
Gestational hypertension 20 (22) 14 (29) 8 (35) 94 (31) .41 
Preeclampsia 3 (3.3) 5 (10) 2 (8.7) 17 (5.6) .28 
Superimposed preeclampsia 1 (1.1) 1 (2.1) 0 (0) 5 (1.6) .90 
Proteinuria 7 (7.8) 6 (13) 3 (13) 30 (9.9) .70 
Pyelonephritis 0 (0) 0 (0) 0 (0) 2 (0.66) .99 
Preterm birthd 4 (4.4) 2 (4.2) 0 (0) 12 (3.9) .92 
SGA infante 4 (4.4) 1 (2.1) 0 (0) 8 (2.6) .76 
a

Any pregnancy complication occurred in 9 of 23 (39%) patients with grade ≥3 VUR and 124 of 304 (41%) controls (95% CI of the difference −19% to 20%).

b

χ2 test between multiple groups.

c

Comprising essential or gestational hypertension, preeclampsia, proteinuria, or pyelonephritis during the first pregnancy.

d

Delivery before 37 wk of pregnancy.

e

Birth wt <10th percentile for gestational age.

In the present population-based study, we investigated the long-term sequelae of childhood UTIs on the basis of the assumption that pregnancy could reveal latent renal damage. UTIs in childhood were not, however, shown to increase the risk of pregnancy complications in adulthood. The risk of essential or gestational hypertension, preeclampsia, proteinuria, and pyelonephritis during pregnancy similarly did not differ between the women with a UTI in childhood and the control women.

The present results are in line with earlier investigations into the long-term sequelae of childhood UTIs. In an earlier controlled study, no risk of hypertension or impaired renal function 6 to 17 years after a childhood UTI was found, although follow-up ultrasonography did reveal unilateral renal scars in up to 15% of the cases.10  Accordingly, Salo et al5  showed that children with structurally normal kidneys in imaging examinations after the first UTI in childhood do not have any increased risk of developing chronic kidney disease as adults.

Most of the previous studies of the impact of childhood UTIs on pregnancy complications have been based on small series of patients from tertiary referral hospitals without any controls (Table 5).1117  To the best of our knowledge, there is only 1 case-control study of pregnancy outcomes in women with childhood UTIs, comprising a total of 41 women, in which Martinell et al7  observed no difference in the occurrence of preeclampsia, prematurity, and low birth weight between 41 women with a history of childhood UTI and 65 control women.

TABLE 5

Previous Studies of Pregnancy Complications in Women With a History of UTI

StudyPopulationSettingWomen, nPregnancies, nControls, nPyelonephritis,an (%)Hypertension, n (%)Preeclampsia, n (%)Low Birth Wt, n (%)Prematurity, n (%)
Martinell et al7  Women with a history of UTI and at risk (N = 111) Tertiary referral center 41 65 65 NR NR No difference No difference No difference 
Austenfeld and Snow11  Women who had undergone ureteroneocystostomy for primary VUR (N = 67) Hospital 30 64 5 of 30 (17) NR NR NR NR 
Beetz et al12  Patients who underwent surgery for VUR in childhood (N = 160) Hospital 28 46 NR NR 3 of 46 (6.5) NR NR 
el-Khatib et al13  Patients followed-up for reflux nephropathy and/or primary VUR (N = 137) Hospital 137 345 19 of 345 (5.5) NR 59 of 345 (17) NR NR 
Gebäck et al14  Women with a history of nonobstructive UTI and urographic evidence of renal damage or with recurrent UTIs (N = 72) UTI clinic for adults 72 151 24 without renal damage NR 10 of 151 (6.6); all with renal damage NR No difference No difference 
Jacobson et al15  Children with nonobstructive focal renal scarring in childhood and a history of pyelonephritis (N = 30) Pediatric primary referral center and urologic clinic in tertiary referral center 16 26 NR NR 2 of 16 (13); proteinuria in 4 of 16 (25) NR NR 
Mansfield et al16  Women who underwent childhood ureteral reimplantation for primary VUR (N = 62) and women with primary VUR who did not undergo ureteral reimplantation (N = 21) Hospital 48 with surgery and 19 without surgery 141 with surgery and 75 without surgery 25 of 141 (18) with surgery and 1 of 75 (1.5) without surgery NR NR NR NR 
Marchand et al17  Women >20 y of age operated on for VUR by a single surgeon from 1969 to 2004 (N = 392) Hospital 113 242 10 of 113 (8.8) NR 0 of 113 (0) NR NR 
StudyPopulationSettingWomen, nPregnancies, nControls, nPyelonephritis,an (%)Hypertension, n (%)Preeclampsia, n (%)Low Birth Wt, n (%)Prematurity, n (%)
Martinell et al7  Women with a history of UTI and at risk (N = 111) Tertiary referral center 41 65 65 NR NR No difference No difference No difference 
Austenfeld and Snow11  Women who had undergone ureteroneocystostomy for primary VUR (N = 67) Hospital 30 64 5 of 30 (17) NR NR NR NR 
Beetz et al12  Patients who underwent surgery for VUR in childhood (N = 160) Hospital 28 46 NR NR 3 of 46 (6.5) NR NR 
el-Khatib et al13  Patients followed-up for reflux nephropathy and/or primary VUR (N = 137) Hospital 137 345 19 of 345 (5.5) NR 59 of 345 (17) NR NR 
Gebäck et al14  Women with a history of nonobstructive UTI and urographic evidence of renal damage or with recurrent UTIs (N = 72) UTI clinic for adults 72 151 24 without renal damage NR 10 of 151 (6.6); all with renal damage NR No difference No difference 
Jacobson et al15  Children with nonobstructive focal renal scarring in childhood and a history of pyelonephritis (N = 30) Pediatric primary referral center and urologic clinic in tertiary referral center 16 26 NR NR 2 of 16 (13); proteinuria in 4 of 16 (25) NR NR 
Mansfield et al16  Women who underwent childhood ureteral reimplantation for primary VUR (N = 62) and women with primary VUR who did not undergo ureteral reimplantation (N = 21) Hospital 48 with surgery and 19 without surgery 141 with surgery and 75 without surgery 25 of 141 (18) with surgery and 1 of 75 (1.5) without surgery NR NR NR NR 
Marchand et al17  Women >20 y of age operated on for VUR by a single surgeon from 1969 to 2004 (N = 392) Hospital 113 242 10 of 113 (8.8) NR 0 of 113 (0) NR NR 

NR, not reported.

a

When reported separately.

In earlier studies, researchers have reported patients who had undergone surgery for VUR in childhood to be at risk for a UTI in pregnancy (Table 5).11,12,16,17  One small controlled study found that 40% of surgically treated and 15% of nonoperated women with primary VUR developed a UTI during pregnancy,16  whereas we did not find any significant differences in the pregnancy outcomes between the women with primary VUR and their control women. Renal scarring is detected relatively frequently in both children and adults after a childhood UTI,10  but the clinical significance of scars is not well understood. The number of women in the current study population having renal scarring was low. It is significant, however, that our patients were actively treated surgically for primary VUR, in addition to which they had excellent access to health care and their UTIs had been treated actively. Moreover, a greater number VUR patients with more renal changes might have shown some differences in the pregnancy outcomes.

The risk of pyelonephritis during pregnancy had not increased after childhood UTI in the present cohort, despite the higher risk of a UTI in pregnancy found in women with a history of UTI in 1 previous study conducted in a tertiary referral center.7  One likely reason for this discrepancy is that Martinell et al7  included in their cohort high-risk women who had been admitted and followed-up with in the tertiary referral center, whereas ours was a controlled population-based study.

The strength of the present work lies in its controlled population-based design, combined with the fact that it is one of the largest to date to investigate pregnancy outcomes in women with UTIs in childhood. Furthermore, we collected data from comprehensive registers and reviewed the original antenatal and postnatal medical records of the population. One limitation on the present results is that the statistical power was insufficient for conclusive subgroup analyses between children with renal scarring or recurrent UTIs or pyelonephritis and control subjects.

The fact that UTIs in childhood did not increase the risk of pregnancy-related complications in adult women is used to suggest that childhood UTIs had not caused significant latent renal damage for this to have manifested itself in pregnancy. Thus, UTIs in children without major urinary tract abnormalities appear to have a good long-term prognosis.

Dr Honkila conducted the initial statistical analyses and drafted the initial manuscript; Dr Hannula collected, entered, and checked the clinical data and critically revised the manuscript; Ms Pokka conducted the initial statistical analyses and critically revised the manuscript; Dr Hanni collected and entered clinical data and critically revised the manuscript; Dr Salo conceptualized and designed the study, designed and performed the data collection, and critically revised the manuscript; Dr Renko designed the analysis of pregnancy outcomes and critically revised the manuscript; Dr Vääräsmäki designed the data collection and the analysis of pregnancy-related outcomes and critically revised the manuscript; Dr Perhomaa collected the radiologic data and critically revised the manuscript; Dr Keskimäinen collected the clinical data and critically revised the manuscript; Dr Uhari conceptualized and designed the study, designed and supervised the data collection, and coauthored the manuscript; Dr Tapiainen conceptualized and designed the study, designed and supervised the data collection and analysis, and coauthored the manuscript; and all the authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: Funding by the Alma and K.A. Snellman Foundation, Finland (Drs Honkila, Hannula, and Tapiainen), the Foundation for Paediatric Research, Finland (Dr Hannula, Prof Renko, and Dr Tapiainen), and the Academy of Finland (Dr Tapiainen). None of these sources had any role in the design or execution of the study.

     
  • CI

    confidence interval

  •  
  • RR

    relative risk

  •  
  • RUS

    renal and urinary tract ultrasonography

  •  
  • SGA

    small for gestational age

  •  
  • UTI

    urinary tract infection

  •  
  • VCUG

    voiding cystourethrography

  •  
  • VUR

    vesicoureteral reflux

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.