Clinical Care/Education/Nutrition/Psychosocial Research ORIGINAL ARTICLE

Diabetic Nephropathy and in Pregnant Women With Type 1 and Type 2 Prevalence, antihypertensive strategy, and pregnancy outcome

1,2 1,2 JULIE AGNER DAMM, MD LENE RINGHOLM, MD, PHD In pregnant women with type 1 di- 1,2 1,4 BJÖRG ASBJÖRNSDÓTTIR, MD BERIT WOETMANN PEDERSEN, MD 1,2 1,2,3 abetes, nephropathy is associated with NICOLINE FOGED CALLESEN ELISABETH R. MATHIESEN, MD, DMSC 1,2 poor pregnancy outcome in terms of JONATHAN M. MATHIESEN increased rates of preeclampsia and pre- term delivery (11–13). In these women, d intrauterine growth restriction (11) oc- OBJECTIVE To evaluate the prevalence of diabetic nephropathy and microalbuminuria in curs almost twice as often as in the general pregnant women with in comparison with and to describe population (13), and in the late 1990s, pregnancy outcomes in these women following the same antihypertensive protocol. preterm delivery before 34 weeks oc- RESEARCH DESIGN AND METHODSdAmong 220 women with type 2 diabetes and curred in ;30% (13). In women with 445 women with type 1 diabetes giving birth from 2007–2012, 41 women had diabetic ne- type 1 diabetes and microalbuminuria, phropathy (albumin- ratio $300 mg/g) or microalbuminuria (albumin-creatinine ratio preterm delivery and preeclampsia are 30–299 mg/g) in early pregnancy. Antihypertensive therapy was initiated if also frequent and serious complications $ $ 135/85 mmHg or albumin-creatinine ratio 300 mg/g. (11,13,14). RESULTSdThe prevalence of diabetic nephropathy was 2.3% (5 of 220) in women with type 2 In nonpregnant subjects with diabe- diabetes and 2.5% (11 of 445) in women with type 1 diabetes (P =1.00).Thefigures for micro- tes, inhibition of the renin angiotensin were 4.5 (10 of 220) vs. 3.4% (15 of 445) (P = 0.39). Baseline glycemic control was system is a cornerstone in the treatment of comparable between women with type 2 diabetes (n = 15) and type 1 diabetes (n =26).Blood microalbuminuria and diabetic nephrop- pressure at baseline was median 128 (range 100–164)/81 (68–91) vs. 132 (100–176)/80 (63– athy (15–19). However, during preg- 100) mmHg (not significant) and antihypertensive therapy in type 2 versus type 1 diabetes was nancy, antihypertensive therapy is often used in 0 and 62%, respectively, at baseline, increasing to 33 and 96%, respectively, in late not indicated until sustained blood pres- pregnancy. Pregnancy outcome was comparable regardless type of diabetes; gestational age at sure elevations .150 mmHg systolic or delivery: 259 days (221–276) vs. 257 (184–271) (P = 0.19); birth weight 3,304 g (1,278–3,914) – 100 mmHg diastolic are documented vs. 2,850 (370 4,180) (P =0.67). (20), owing to concerns for reduced pla- CONCLUSIONSdThe prevalence of diabetic nephropathy and microalbuminuria in early cental circulation, which may cause fetal pregnancy was similar in type 2 and type 1 diabetes. Antihypertensive therapy was used more hypoxia and intrauterine growth restric- frequently in type 1 diabetes. Pregnancy outcome was comparable regardless type of diabetes. tion (21). In Copenhagen, we recommend blood pressure levels ,135/85 mmHg and urinary albumin-creatinine ratio outh onset of type 2 diabetes con- type 1 diabetes (6). Literature focusing ,300 mg/g during pregnancy in women Ytinues to increase worldwide (1), on involvement in pregnant with diabetes and diabetic nephropathy and pregnancy in women with womenwithdiabetesisscarce(7–11). or microalbuminuria (14,22), regardless type 2 diabetes is a substantial clinical To our knowledge, no studies using strict of the type of diabetes. Using this strategy, problem (2). Cross-sectional studies diagnostic criteria have described the observational studies have shown that show a higher prevalence of albuminuria prevalence of diabetic nephropathy and early initiation of intensive antihyperten- in young adults with type 2 diabetes com- microalbuminuria in early pregnancy in sive therapy during pregnancy leads to a pared with type 1 diabetes (3–5). Subjects women with type 2 diabetes. Likewise, reduced prevalence of preterm delivery in with youth-onset type 2 diabetes have a recommendations for an antihypertensive women with type 1 diabetes and diabetic fourfold increased risk of end-stage kid- strategy during these pregnancies is miss- nephropathy or microalbuminuria ney disease compared with youth with ing. (14,22). Brown and Garovic (23) also recommend a lower threshold for antihy- ccccccccccccccccccccccccccccccccccccccccccccccccc pertensive treatment in pregnant women From the 1Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark; the 2De- with diabetes and kidney involvement partment of , Rigshospitalet, Copenhagen, Denmark; the 3Faculty of Health Sciences, compared with nondiabetic pregnant University of Copenhagen, Denmark; and the 4Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark. women. Corresponding author: Julie Agner Damm, [email protected]. However, it has not been evaluated Received 1 May 2013 and accepted 16 June 2013. whether women with type 2 diabetes DOI: 10.2337/dc13-1031 benefit from intensive antihypertensive © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly therapy to the same degree as women cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/ licenses/by-nc-nd/3.0/ for details. with type 1 diabetes during pregnancy.

care.diabetesjournals.org DIABETES CARE 1 Diabetes Care Publish Ahead of Print, published online September 5, 2013 Nephropathy and pregnancy in type 2 diabetes

In this study, we evaluated the prev- weight, HbA1c, dose, and blood death (death occurring between 22 com- alence of diabetic nephropathy and mi- pressure were recorded, and the urine pleted weeks and 1 completed week after croalbuminuria as well as pregnancy was screened for with a dip- delivery), low 5-min Apgar score (,7), outcome in a recent cohort of pregnant stick test (Urinstix; Bayer Diagnostics, transient tachypnea of the newborn (the women with type 2 or type 1 diabetes Bridgend, U.K.) on sterile urine. Further need of continuous positive airway pres- treated according to the same protocol for analysis of urinary albumin-creatinine ra- sure for .1 h), neonatal intensive antihypertensive treatment dur- tio was performed if proteinuria (.1+ on (plasma glucose ,2.5 mmol/L) on the ing pregnancy. the dipstick) was present. The urinary al- first plasma glucose value measured 2 h bumin excretion was analyzed using an after delivery, or neonatal jaundice (need RESEARCH DESIGN AND ELISA (26), and the blood creatinine con- of photo therapy). Birth weight was eval- METHODSdA retrospective cohort centration was measured by standard lab- uated by calculating SD z score to adjust study among 665 singleton pregnancies oratory methods. for gestational age and sex and small- and in women with type 2 or type 1 diabetes Blood pressure was measured with a large-for-gestational age (weight for ges- with a living fetus at 22 weeks delivering digital blood pressure monitor (A&D In- tational age ,10th percentile and .90th at our center from January 2007 until struments, Abingdon, U.K.) in a sitting percentile, respectively) (28). October 2012 was conducted. The center position after 5–10 min of rest. The study was approved by the Dan- is a referral center for all pregnant women If urinary albumin-creatinine ratio ish Data Protection Agency. According to with type 2 or type 1 diabetes from a was $300 mg/g or blood pressure Danish law, the regional committees for geographically well-defined area of 2.5 $135/85 mmHg, antihypertensive ther- ethics and science did not have to be million inhabitants. All women were apy was initiated or intensified. If ACE contacted. askedtobringtwourinesamplesfor inhibitors were withdrawn during pre- analysis of urinary albumin excretion at pregnancy planning, another antihyper- Statistics the first pregnancy visit. Urinary albu- tensive therapy was initiated unless the Data are given as median (range) or n (%). min-creatinine ratio was used in the urinary albumin-creatinine ratio was Differences between groups were ana- majority of cases to evaluate kidney in- close to normal (22). lyzed using Fisher exact test and x2 test, volvement since we previously reported a Methyldopa (14,27) was the first- as appropriate, for categorical variables high concordance between albumin ex- choice therapy in most cases, and, when and Mann-Whitney test for continuous cretion in 24-h urine collection and uri- indicated, labetalol and/or nifedipine (14) variables as data were nonnormally dis- nary albumin-creatinine ratio (24). At were added. If given before pregnancy, tributed. least two values within the range of micro- furosemide or thiazide was continued The associations were considered to albuminuria or diabetic nephropathy during pregnancy to reduce the risk of re- be statistical significant at a two-sided P were required to classify the patients. bound fluid retention with increased value ,0.05. All statistical analyses were Forty-one women were identified with blood pressure and urinary albumin ex- performed using SPSS statistics 20.0 kidney involvement defined as presence cretion when discontinuing the drug (SPPS, Chicago, IL). of diabetic nephropathy (urinary albu- (14,22). min-creatinine ratio $300 mg/g) or mi- Nonstress testing with cardiotocogra- RESULTSdThe prevalence of diabetic croalbuminuria (urinary albumin- phy was used routinely at least once nephropathy at baseline was 2.3% (5 of creatinine ratio 30–299 mg/g). At the first weekly from 32–34 gestational weeks in 220) in women with type 2 visit, three women had ne- addition to daily kick-counting. Fetal 2.5% (11 of 445) in women with type 1 phrotic proteinuria (urinary albumin-cre- growth was evaluated routinely by obstet- diabetes (P = 1.0). The prevalence of mi- atinine ratio .2,000 mg/g). rical ultrasound at 28, 33, and 37 weeks croalbuminuria was 4.5 (10 of 220) vs. One woman with type 1 diabetes and of gestation. On clinical indications as 3.4% (15 of 445), respectively (P = diabetic nephropathy had two pregnan- judged by the obstetrician, flow measure- 0.39), giving a total prevalence of kidney cies in the inclusion period; both preg- ments of the umbilical, cerebral, and uter- involvement in early pregnancy of 6.8% nancies were included to ensure all ine arteries were performed. for type 2 diabetes vs. 5.8% for type 1 available cases in the study period. Preeclampsia was defined as two re- diabetes (P = 0.62). Women were recommended to per- cordings of either systolic blood pressure Baseline characteristics (Table 1) were form self-monitored plasma glucose $140 mmHg or diastolic blood pressure comparable between women with kidney (SMPG) values seven times daily, before $90 mmHg and urinary albumin excre- involvement with either type 2 diabetes and90minaftereachmainmealand tion .190 mg/24 h or proteinuria $1+ (n = 15) or type 1 diabetes (n = 26), except before bedtime, and they were instructed on a dipstick of sterile urine after 20 for shorter duration of diabetes in women to change insulin dose based on the weeks of gestation. In women with dia- with type 2 diabetes. Elevated urinary al- SMPG values of the previous 3 days. betic nephropathy, the diagnosis was ad- bumin excretion rate was documented Treatment targets were: preprandial ditionally based on a sudden increase of with two urine samples before 20 weeks SMPG of 4.0–6.0 mmol/L, 90-min post- $15% in systolic or diastolic blood pres- in the majority of cases and with one urine prandial SMPG of 4.0–8.0 mmol/L, and sure (12). sample in the remaining. prebedtime SMPG of 6.0–8.0 mmol/L Neonatal outcomes included early Glycemic control was similar in (25). HbA1c #5.6% in the second part preterm delivery before 34 weeks, pre- women with type 2 and type 1 diabetes of pregnancy was recommended (25). term delivery before 37 weeks, major (Table 1). At first pregnancy visit, antihy- The women visited our and/or their congenital malformations (responsible pertensive therapy was not used in any of local diabetes clinic mainly at 2-week for death, causing a significant future the women with type 2 diabetes and in 16 intervals during pregnancy. At each visit, handicap, or requiring surgery), perinatal

2 DIABETES CARE care.diabetesjournals.org Damm and Associates

Table 1dMaternal characteristics among 41 women with type 2 diabetes or type 1 diabetes and kidney affection during pregnancy

Diabetic nephropathy Microalbuminuria Type 2 diabetes Type 1 diabetes Type 2 diabetes Type 1 diabetes N 5111015 Maternal age (years) 31 (21–39) 32 (28–40) 31 (23–37) 31 (22–37) Diabetes duration (years) 2 (0.5–13) 19 (10–34)** 2 (0.5–8) 22 (10–31)** Nullipara 2 (50) 5 (45) 3 (30) 10 (67) Maternal smoking 0% 3 (27) 3 (30) 4 (27) Folic acid at first visit 2 (50) 10 (91) 6 (60) 12 (92) Gestational age at first visit (days) 66 (44–69) 68 (49–95) 84 (47–122) 55 (42–147)* BMI before pregnancy (kg/m2) 28.2 (24.7–39.3) 23.7 (18.9–34.7) 31.4 (22.5–43.3) 25.8 (21.2–37.5) HbA1c at first visit (%) 6.8 (5.5–13.2) 7.0 (6.0–9.4) 6.8 (5.8–8.8) 7.1 (6.0–8.3) fi – – – – HbA1c at rst visit (mmol/mol) 51 (37 121) 53 (42 79) 51 (40 73) 54 (42 67) HbA1c at last visit (%) 5.5 (5.2–5.9) 6.1 (5.5–6.7) 6.2 (5.6–8.2) 6.3 (5.3–6.6) HbA1c at last visit (mmol/mol) 37 (33–41) 43 (37–50) 44 (38–66) 45 (34–49) at first visit 3 (75) 5 (56) 2 (20) 11 (85)** Serum creatinine at first visit (mmol/L) 52 (40–73) 61 (34–168) 40 (31–63) 51 (35–87)* Albumin-creatinine ratio at first visit (mg/g) 474 (350–2,950) 712 (350–3,000) 110.5 (51–206) 84.5 (33–222) Two urine samples collected before 20 weeks 5 (100) 11 (100) 7 (70) 12 (80) Antihypertensive therapy at first visit 0 7 (64) 0 9 (60)** Systolic blood pressure at first visit (mmHg) 132 (100–164) 140 (97–176) 128 (108–149) 132 (107–155) Diastolic blood pressure at first visit (mmHg) 88 (73–91) 80 (63–100) 78 (68–88) 80 (68–87) Weight gain during pregnancy (kg) 16.7 (2.5–28) 9.25 (1.3–16.2) 8.25 (22.2 to 15.1) 11.7 (21.5 to 24.9) Insulin dose at first visit (IU/kg) 0.40 (0–0.62) 0.68 (0.37–1.17) 0.35 (0–1.23) 0.72 (0.46–1.51)

Data are median (range) or n (%). aOnly few data available (3 of 10). *P , 0.05, **P , 0.001.

(62%) women with type 1 diabetes (P , Development of nephrotic proteinuria (10%) infants of women with kidney in- 0.001). during pregnancy occurred in one volvement. In women with type 2 diabetes, anti- (2.4%) woman with type 1 diabetes and Major congenital malformations were hypertensive therapy was initiated during diabetic nephropathy. recorded in two infants (5%); one live- pregnancyinfour(80%)womenwith Among all 41 women, 11 (27%) re- diabetic nephropathy and in two (20%) ceived low-dose aspirin during pregnancy women with microalbuminuria. Antihy- evenly distributed among the four pertensive therapy was mainly initiated in groups. Five (20%) women with type 1 early pregnancy. In two (40%) women diabetes were treated with thyroid hor- with diabetic nephropathy, at least three mone replacement for hypothyroidism classes of antihypertensive drugs were during pregnancy. None received antide- indicated. pressant therapy. Among women with type 1 diabetes, Abnormal flow was measured by nine were treated with ACE inhibitors ultrasound in four women with type 1 before pregnancy, and eight continued diabetes (three with nephropathy and one this treatment during the organogenesis. with microalbuminuria) and was a con- Antihypertensive therapy was initiated or tributing factor to induced preterm de- continued during pregnancy in 25 of 26 liverybasedonobstetricaljudgment. women, and 14 (54%) women received at Three of these four women received least two classes of drugs. In women with antihypertensive treatment. diabetic nephropathy, six (55%) received None of the routine nonstress tests at least three classes of drugs. The max- alone led to induction of labor or cesarean imum number of antihypertensive drugs section before planned. given was four. Pregnancy outcome was comparable Blood pressure was stable during in women with type 2 and type 1 diabetes pregnancy in all groups without statisti- (Table 2). The main causes for preterm cally significant differences (Fig. 1). delivery were preeclampsia, macrosomia, In early pregnancy, serum creatinine or suspected placental insufficiency. In Figure 1dBlood pressure during pregnancy was within normal range in all women, women with type 2 and type 1 diabetes, among 41 women with type 2 (T2DM) or type except three (Table 1), and remained sta- birth weight was 3,304 g (1,278–3,914) 1 diabetes (T1DM). A: Women with nephrop- ble during pregnancy. No women devel- and 2,850 (370–4,180), respectively (P = athy. B: Women with microalbuminuria. Data oped end-stage . 0.67). Birth weight was ,2,000 g in four are expressed as median and interquartile range. care.diabetesjournals.org DIABETES CARE 3 Nephropathy and pregnancy in type 2 diabetes

Table 2dPregnancy outcome among 41 pregnancies in women with type 2 or type 1 diabetes and kidney affection during pregnancy

Diabetic nephropathy Microalbuminuria Type 2 diabetes Type 1 diabetes Type 2 diabetes Type 1 diabetes N 5111015 Preeclampsia 2 (40) 4 (36) 1 (10) 3 (20) Cesarean section 3 (60) 10 (91) 8 (80) 12 (80) Gestational age at delivery (days) 250 (233–276) 249 (184–259) 260 (221–275) 259 (224–271) Delivery before 37 weeks 3 (60) 9 (82) 3 (30) 7 (47) Delivery before 34 weeks 2 (40) 3 (27) 1 (10) 1 (7) Birth weight (g) 2,460 (1,835–3,314) 2,506 (370–3,740) 3,355 (1,278–3,914) 3,229 (2,138–4,180) Admission to neonatal special care unit 3 (60) 7 (64)* 4 (44) 5 (33) Neonatal hypoglycemia (,2.5 mmol/L) 1 (25) 8 (89) 3 (33) 5 (36) Weight z score (SD units) 20.51 (21.6 to 0.9) 20.84 (25.3 to 3.0) 1.21 (22.8 to 2.4) 1.40 (21.3 to 3.8) Large-for-gestational-ageinfants 0 2(18) 3(30) 8(53) Small-for-gestational-age infants 2 (40) 4 (36) 2 (20) 1 (7)

Data are median (range) or n (%). *P , 0.05, **P , 0.001. born with hypospadias (the mother re- with a relatively shorter duration of di- general practitioner and were rarely fol- ceived ACE inhibitor during the organo- abetes (3–5). lowed at a specialized diabetes center. genesis), and one stillborn with multiple In Danish pregnant women with type This may explain the lack of antihyper- kidney and heart malformations (no inhi- 1 diabetes, the prevalence of diabetic tensive treatment in women with type 2 bition of the renin angiotensin system nephropathy has declined from 5% in diabetes and diabetic nephropathy or during organogenesis). One infant with the late 1990s (12) to 2.5% in the current microalbuminuria at the first pregnancy severe intrauterine growth restriction (z study, in which the same diagnostic crite- visit. score 25.25) and abnormal umbilical ria was used. The prevalence of diabetic The strength of this study is that the flow was delivered at 30 weeks and died nephropathy in type 1 diabetes in the cur- data are unselected from one large center 3 days postpartum. The mother had type rent study is in accordance with a preva- covering the entire eastern part of Den- 1 diabetes and diabetic nephropathy and lence of 0.5–5.0% in other recent studies mark. The same intensive antihyperten- was treated with three antihypertensive using slightly different diagnostic criteria sive strategy was used during the whole agents during pregnancy. One year later, for diabetic nephropathy (7–9,29). The period, and the same few doctors treated this woman completed an uneventful figures for type 2 diabetes were 0.8 and all patients. Blood pressure was almost pregnancy while receiving four types of 2.6% (8,9). stable during pregnancy in all groups antihypertensive agents. The prevalence of microalbuminuria without statistically significant differen- in Danish pregnant women with type 1 ces, but numbers were too small for firm CONCLUSIONSdThis study demon- diabetes has declined from 11% in the conclusions. Glycemic control was gen- strates that the prevalence of diabetic 1990s (12) to 4.5% in the current study, erally good, contributing to affect preg- nephropathy and microalbuminuria in using the same diagnostic criteria. This is nancy outcome positively (36). pregnant women with type 2 diabetes in accordance with international findings The low number of cases, despite the was comparable to the prevalence in reporting prevalence of microalbuminu- long inclusion period, and the retrospec- pregnant women with type 1 diabetes. ria in pregnant women with type 1 diabe- tive design of the study are weaknesses. Using the same antihypertensive strategy, tes between 10 and 30% in the late 1990s We asked all women for two urine sam- pregnancy outcome was comparable re- (11,30) and recent findings of 4.5% (29). ples at the first pregnancy visit. The gardless type of diabetes in women with For pregnant women with type 2 majority of women were compliant to kidney involvement. Antihypertensive diabetes, the prevalence of microalbumi- this request; in women with diabetic therapy was used more frequently in nuriainthelate1990swas13(2)and nephropathy, it was 100%, but among women with type 1 diabetes and did not 33% (31). women with microalbuminuria, two sam- seem to affect pregnancy outcome nega- The decline in prevalence of diabetic ples were obtained in 70–80% of the ca- tively. nephropathy and microalbuminuria in ses. Some of these women might have had The women with type 2 diabetes and women with type 1 diabetes is in line normal urinary albumin excretion in the kidney involvement had a relatively with a general trend toward lower prev- next sample, which could lead to a shorter diabetes duration compared with alence of diabetic nephropathy in the slightly lower prevalence of microalbumi- the women with type 1 diabetes. This is in Danish diabetic population (32). This nuria. For clinicians caring for these high- accordance with the findings in the non- may be explained by improved glycemic risk pregnancies, it is clinically relevant to pregnant population of children and control (33,34) and more frequent use of describe the prevalence and pregnancy young adults with type 2 diabetes in inhibitors of the renin angiotensin system outcome in pregnant women with type whom microalbuminuria and diabetic (16,17,35). 2 diabetes and diabetic nephropathy or nephropathy are also present in subjects Preconceptionally, women with type microalbuminuria, as this group of pa- 2 diabetes are mainly followed at the tients is expected to increase in the near

4 DIABETES CARE care.diabetesjournals.org Damm and Associates future. Pregnancy outcome, especially Pregnancy outcome was comparable in diabetes. Diabetes Care 2012;35:1265– preterm delivery and preeclampsia, were women with kidney involvement regard- 1271 in accordance to our previous results (22) less type of diabetes. It seems reasonable 7. Landon MB. Diabetic nephropathy and pregnancy. Clin Obstet Gynecol 2007;50: using the same antihypertensive protocol to assume that pregnant women with – in pregnant women with type 1 diabetes diabetic nephropathy or microalbuminu- 998 1006 8. Murphy HR, Steel SA, Roland JM, et al. and diabetic nephropathy or microalbu- ria could be treated and controlled in a Obstetric and perinatal outcomes in minuria. Thus, this study supports that similar way regardless type of diabetes. fi pregnancies complicated by type 1 and intensi ed antihypertensive treatment re- type 2 diabetes: influences of glycaemic duces adverse pregnancy outcome as pre- control, obesity and social disadvantage. viously described in women with type 1 AcknowledgmentsdNo potential conflicts of Diabet Med 2011;28:1060–1067 diabetes and nephropathy (11,37) or mi- interest relevant to this article were reported. 9. Bell R, Glinianaia SV, Tennant PW, Bilous J.A.D. researched data, wrote the manu- croalbuminuria (14). RW, Rankin J. Peri-conception hyper- Serum creatinine was used as an in- script, and contributed to discussions. B.A. glycaemia and nephropathy are associated dex of renal function. We found stable and N.F.C. researched data, contributed to with risk of congenital anomaly with discussions, and reviewed and edited the serum creatinine levels during pregnancy preeisting diabetes: a population-based manuscript. J.M.M., L.R., and B.W.P. con- cohort study. Diabetologia 2012;55:936– for both women with diabetic nephropa- tributed to discussions and reviewed and 947 thy and microalbuminuria, regardless edited the manuscript. E.R.M. contributed to 10. Kitzmiller JL, Combs CA. Diabetic ne- type of diabetes in accordance with earlier the idea, researched data, contributed to dis- phropathy and pregnancy. Obstet Gyne- findings (22,38). cussions, and reviewed and edited the manu- col Clin North Am 1996;23:173–203 The use of intensive antihypertensive script. E.R.M. is the guarantor of this work 11. Jovanovic L, Inturissi M. Assessment of therapy during pregnancy may raise con- and, as such, had full access to all the data in glycemic control. In Managing Preexisting cern about fetal intrauterine growth re- the study and takes responsibility for the in- Diabetes Mellitus for Pregnancy. Kitzmiller striction by lowering the placental blood tegrity of the data and the accuracy of the data JL, Ed. Alexandria, VA, American Diabetes – flow. In women with microalbuminuria, analysis. Association, 2008, p. 379 386 This study was presented as a poster at Di- median birth weight z score was positive 12. Ekbom P, Damm P, Feldt-Rasmussen B, fi abetes, , Metabolic Syndrome Feldt-Rasmussen U, Mølvig J, Mathiesen in both groups, indicating suf cient fetal and Pregnancy, Florence, Italy, 14–16 March ER. Pregnancy outcome in type 1 diabetic growth despite antihypertensive therapy 2013 and in abstract form at the North Europe women with microalbuminuria. Diabetes given in 68% of these women. Young Diabetologists meeting, Korsør, Den- Care 2001;24:1739–1744 Theprevalenceofsmall-for-gesta- mark, 28–30 August 2013. 13. Dunne FP, Chowdhury TA, Hartland A, tional age infants in women with diabetic et al. Pregnancy outcome in women with nephropathy was 40 and 36% for type 2 insulin-dependent diabetes mellitus and type 1 diabetes, respectively, which is References complicated by nephropathy. QJM 1999; in accordance with our earlier findings 1. Dart AB, Sellers EA, Dean HJ. Kidney 92:451–454 € (12). The high rate of small-for-gesta- disease and youth onset type 2 diabetes: 14. Nielsen LR, Muller C, Damm P, Mathiesen tional-age infants is most likely explained considerations for the general practi- ER. Reduced prevalence of early preterm tioner. Int J Pediatr 2012;2012:237360 delivery in women with Type 1 diabetes by the diabetic per se 2. Clausen TD, Mathiesen E, Ekbom P, and microalbuminuriadpossible effect of (39). Hellmuth E, Mandrup-Poulsen T, Damm early antihypertensive treatment during To evaluate properly whether initia- P. Poor pregnancy outcome in women pregnancy. Diabet Med 2006;23:426–431 tion of antihypertensive therapy affects with type 2 diabetes. Diabetes Care 2005; 15. Parving H-H, Smidt UM, Hommel E, et al. uteroplacental and fetal hemodynamics in 28:323–328 Effective antihypertensive treatment diabetic pregnancy, a prospective study 3. Eppens MC, Craig ME, Jones TW, Silink postpones renal insufficiency in diabetic with nonstress tests and careful ultra- M, Ong S, Ping YJ; International Diabetes nephropathy. Am J Kidney Dis 1993;22: fi sound examinations before and after ini- Federation Western Paci c Region Steer- 188–195 ing Committee. Type 2 diabetes in youth 16. Mathiesen ER, Hommel E, Giese J, Parving tiation of antihypertensive therapy is fi fi needed. from the Western Paci c region: glycae- H-H. Ef cacy of in postponing mic control, diabetes care and complica- nephropathy in normotensive insulin de- In women with increased risk of pre- tions. Curr Med Res Opin 2006;22:1013– pendent diabetic patients with micro- eclampsia, including pregestational dia- 1020 albuminuria. BMJ 1991;303:81–87 betes complicated with diabetic 4. Scott A, Toomath R, Bouchier D, et al. 17. Mathiesen ER, Hommel E, Hansen HP, nephropathy or microalbuminuria, treat- First national audit of the outcomes of Parving H-H. 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