Övervikt vid graviditet och förlossning Marie Blomberg Professor Överläkare Kvinnokliniken Linköping

Tabell 4.5. BMI hos gravida kvinnor vid inskrivning i mödrahälsovård per län, 2016

Graviditetsregistret 2018

Medel BMI vid inskrivning över tid

BMI och risken för missbildning Blomberg et al. Birth Defects Res A Clin Mol Teratol. 2010

Fetma klass I-III och risken för missbildning hos fostret 1995 to 2007 MFR 1995 to 2007 Blomberg et al Birth Defects Res A Clin Mol Teratol 2010

2001 to 2014 2001 to 2014 Persson M et al BMJ. 2017

Fetma och missbildning-mekanismer? Metabola förändringar: insulinresistens, hyperinsulinemi, latent diabetes typ II, hyperglykemi Brist på näringsämnen: bantning, näringsfattig kost Inflammation

BMI och % suboptimal ultraljudsbild Hendler et al IntJ Obes Relat Metab Disord 2004

Impact of maternal body mass index on the antenatal detection of congenital anomalies  Trends in the percentage of suspected cases and the percentage of cases ending in termination of pregnancy across body mass index (BMI) categories (chromosomal and teratogenic syndromes were excluded). P values calculated using Cuzick’s test for trend. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. Best et al BJOG 2012 Volume 119, Issue 12, pages 1503-1511.

Andelen hjärtmissbildningar som upptäcktes i FaSTER trial Prospektiv multicenterstudie BMI<25 21,6% BMI>30 8,3% Aagaard-Tillery KM, et al. FaSTER trial Prenat Diagn 2010

Practice Points-second-trimester anatomic evaluation in obese women They should be counseled on the lower detection rate and increased residual risk due to poor visualization. The optimal timing of ultrasound is between 18 and 24 weeks Experienced sonographers Repeat examination and more advanced equipment may improve visualization Using an ultrasound window with the shortest depth of subcutaneous adipose tissue can improve visualization Tsai P, et al. Best Pract Res Clin Obstet Gynaecol. 2015.

GDM För varje ökning av BMI med 5 enheter ökar risken för GDM med 48% Torloni et al Obes Rev 2009 Singh et al J Matern Fetal Neonatal Med 2012

Graviditetshypertoni/preeklampsi Fetmaklass I 10% Fetmaklass II 12,8% Fetmaklass III 16,3 % Fetmaklass I 10,2% Fetmaklass II och III 12,3% Weiss et al Am J Obstet Gynecol 2004 Schummers et al Obstet Gynecol 2015

Impact of maternal body mass index on PIH, preeclampsia ,GDM a meta‐analysis of European, North American, and Australian cohorts Maternal pre‐pregnancy body mass index and the risks of pregnancy complicationsa. aValues are odds ratios, 95% confidence intervals) on a log scale from multilevel binary logistic regression models that reflect the risk of pregnancy complications per pre‐pregnancy BMI group compared with the reference group (largest group, 20.0–22.4 kg/m2). The bars represent the percentage of each pregnancy complication per BMI group. Mothers diagnosed with pre‐eclampsia were excluded from the models for gestational hypertension. The reference group for the analyses on pre‐eclampsia comprises the mothers without both pre‐eclampsia and gestational hypertension. The reference group for the analyses on small and large for gestational age at birth is appropriate size for gestational age at birth. Models are adjusted for maternal age, educational level, parity, and smoking habits during pregnancy. Models for birth complications are additionally adjusted for child's sex. The EXCEL trendline function was used to fit the curve to the data. The risks of pregnancy complications per kg/m2 were: gestational hypertension (OR 1.11, 95% CI 1.11–1.12), pre‐eclampsia (OR 1.11, 95% CI 1.11–1.12), gestational diabetes (OR 1.12, 95% CI 1.12–1.13), preterm birth (OR 1.02, 95% CI 1.01–1.02), small size for gestational age at birth (OR 0.96, 95% CI 0.95–0.96), and large for gestational age at birth (OR 1.08, 95% CI 1.08–1.08). IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. BJOG: An International Journal of Obstetrics & Gynaecology, First published: 20 February 2019, DOI: (10.1111/1471-0528.15661) Santos S et al BJOG 2019

Copyright © 2012 American Medical Association. All rights reserved. From: Maternal Obesity and Risk of Preterm Delivery Cnattingius et al 2013 JAMA. 2013;309(22):2362-2370. doi:10.1001/jama.2013.6295 En kvinna med sjuklig fetma har 4 gånger ökad risk att föda extremprematurt på grund av medicinskt inducerad förlossning, men också fördubblad risk att föda spontant Copyright © 2012 American Medical Association. All rights reserved.

IUFD Den fetmarelaterade risken är mest uttalad i fullgången graviditet och vid överburenhet Mekanismen? ökat inflammatoriskt svar placentainsufficiens onormal metabol profil Riskökning IUFD Stephansson 2001, Cnattingius –98 och Kristensen-05 Aarhus Cedergren Obstet Gynecol 2004 Woolner et al Best Pract Res Clin Obstet Gynaecol 2015

Prepregnancy maternal body mass index and venous thromboembolism: a population‐based cohort study Prevalence of venous thromboembolism among antepartum, delivery, and postpartum cohorts. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. BJOG: An International Journal of Obstetrics & Gynaecology, Volume: 126, Issue: 5, Pages: 581-588, First published: 30 November 2018, DOI: (10.1111/1471-0528.15567) Butwick et al BJOG 2019

Adjusted for: smoking in early pregnancy, calender year of delivery, maternal age, maternal comorbidity. PE and CS also adjusted for GA GA also adjusted for PE Shoulder dystocia and OASI also adjusted for birthweight. Ramo Isgren et al 2017.

Ramo Isgren et al 2017.

Overweight adolescents compared with standard women Ramo Isgren et al 2017.

Adolescents compared with the standard women

Förlossningskomplikationer Riskökning Cedergren Obstet Gynecol 2004

Indikation för akut kejsarsnitt BMI Värkrubbning O62-63 Obstruktion O64-66 <20 0.57* 1.05 20-24.9 referens 25-29.9 1.50* 1.08 30-34.9 2.15* 1.65 35-39.9 2.69* >40 4.05* 1.56 Cedergren Eur J Obstet Gynecol Reprod Biol 2009

Förlossningstid Normalvikt 8,8h Klass I 9,1h Klass II 9,2h Klass III 9,8h Kaplan Meier: Tiden i aktiv förlossning (timmar) i relation till BMI. Korrigerat för ålder och barnvikt Carlhäll et al Eur J Obstet Gynecol Reprod Biol 2013 25

BMI och tid i latensfas/aktiv förlossning efter induktion Adjustments were made for birth-weight and gestational weight gain. P for difference between BMI-groups <0.001   Adjustments were made for maternal age, birth-weight, gestational weight gain and smoking in early pregnancy. P for difference between BMI-groups <0.001. Carlhäll et al Submitted

Försämrad kontraktilitet hos obesa? Myometriet kontraherar sig med minskad frekvens och amplitud. Även förändringar i Cajonflödet. Zhang: England. 73 biopsier vid elektiva snitt (förstisar och flerpara). Spontana kontraktioner i myometriesträngar. (Higgins et al Reproductive Scienes 2010- Storbritannien. 609 stripes, 85 women (el sectio v 37+) Fann ingen korrelation mellan BMI –kontr) The force and Ca2+ in spontaneously contracting myometrial strips taken from women having elective caesarean section at term (top). The amplitude and frequency of contractions from underweight (uw), BMI <19.9 kg/m2; normal (n), BMI 20–24.9 kg/m2; overweight (ow), BMI 25–29.9 kg/m2; obese (ob), BMI >30 kg/m2. Asterisks indicate statistically significant difference from normal-weight group. Zhang et al BJOG 2007

Vad kan påverka uteruskontraktiliteten hos obesa? Förändrad metabol profil? Leptin och Apelin (adipocytokiner från fettvävnad) utövar en hämmande effekt på kontraktioner i myometriet Hehir. Am J Obstet Gynecol. 2012. Moynihan Am J Obstet Gynecol. 2006 Förändrad förekomst/uttryck av oxytocinreceptorn? Garabedian et al såg en uppreglering av oxytocinreceptorn hos obesa förstföderskor. Grotegut et al fann inget samband Garabedian et al Am J Perinatol 2013 Grotegut et al. Reprod Sci 2013

Fetmaklass och leptinhalt Carlhäll et al. BMC Obesity 2016

Proposed mechanisms of the action of adipokine effects on myometrial contractility. a. Through mitogen-activated protein (MAP) kinase. b. Through activation of nitric oxide synthase. c. Through activation NAD+. d. By direct activation of Ca-activated BK type K channels. e. Through PGE3. f. By direct inhibition of L-type Ca channels. Seham AlSaif, Sadaf Mumtaz, Susan Wray A short review of adipokines, smooth muscle and uterine contractility Life Sciences, Volume 125, 2015, 2–8 http://dx.doi.org/10.1016/j.lfs.2015.02.001

Carlhäll et al. AOGS 2018

BMI och oxytocinreceptorn Correlation of myometrial oxytocin receptor gene expression Myometrial oxytocin receptor protein expression Grotegut et al Reprod Sci 2013

Maternal prepregnancy obesity and the risk of shoulder dystocia: a meta‐analysis Forest plot of relative risks (RRs) with corresponding 95% CIs of studies on maternal prepregnancy obesity and shoulder dystocia. Size of grey box is proportional to weight assigned to each study, and horizontal lines represent 95% CIs. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. For class III obesity versus nonobesity, the pooled RR of shoulder dystocia was 2.47 (95% CI: 1.56–3.93 Zhang et al BJOG 2018 Volume: 125, Issue: 4, Pages: 407-413

BMI och postpartumblödning >1000ml Total N=1,114,071 Blödning >1000ml N=50,565 (%) aOR* 95% CI <18.5 23,524 960 (4.1) 0.95 0.89-1.01 18.5-24.9 596,787 26,594 (4.5) 1.00 Referens 25-29.9 236,602 10,840 (4.6) 1.06 1.03-1.08 30-34.4 73,398 3,382 (4.6) 1.08 1.04-1.12 35-39.9 21,679 1,038 (4.8) 1.13 1.06-1.21 ≥40 7,479 347 (4.6) 0.97-1.20 *ålder, paritet, rökning

Placentaretention Atoni

BMI och postpartumblödning >1000ml OR NS Justerat för ålder, rökning, paritet och födelseår Blomberg Obstet Gynecol 2011

Partiell sfinkterskada aOR 95%CI Total sfinkterskada aOR 95%CI BMI Partiell sfinkterskada aOR 95%CI Total sfinkterskada aOR 95%CI <18.5 1.24 1.14-1.36 1.48 1.27-1.74 18.5-24.9 1 25-29.9 0.92 0.88-0.95 0.90 0.84-0.97 30-34.9 0.90 0.84-0.96 0.77 0.67-0.88 35-39.9 0.79 0.70-0.90 0.65 0.50-0.83 ≥40 0.82 0.66-1.02 0.47 0.28-0.78 Justerat för födelseår, mammans ålder, barnets födelsevikt, fosterläge, instrumentell förlossning Blomberg Biomed Res Int 2014

BMI och AVD/anovaginal distance Hjertberg et al Biomed Res Int 2018

Perinatala komplikationer OR Cedergren Obstet. Gynecol 2004;103:219-24

Vaginal förlossning eller sectio vid högt BMI? Välkända risker för modern vid sectio: Anestesiologiska risker: intubationssvårigheter, hypotoni, otillräcklig effekt av LA Operationskomplikationer: tekniskt komplicerat, blödning Postoperativa: serom, sårruptur, infektion

Neonatal aspiration/lungblödning, sepsis, kramper OR Referens: normalvikt Blomberg Obstet Gynecol 2013

BMI och risken för dåligt neonatalt utfall vid olika förlossningssätt OR NS Blomberg Obstet Gynecol 2013

BMI och postpartuminfektion Sårinfektion Endometrit Bröstböld OR 95% CI 95%CI 25-29.9 1.42 1.31-1.54 1.18 1.12-1.23 0.95 0.88-1.00 30-34.9 2.39 2.16-2.65 1.29 1.21-1.38 0.76 0.68-0.85 ≥35 4.24 3.79-4.74 1.38 1.26-1.53 0.47 0.38-0.59 Term pregnancies 2005-2012. Axelsson et al J Perinat Med 2017

Take home message Ökad risk för missbildning hos fostret Färre missbildningar upptäcks vid ultraljud Oftare preeklampsi och IUFD Livmodern drar ihop sig sämre, längre förlossningstid och fler atoniska blödningar Minskad risk för bäckenbottenskador? Nyfödda barnen har fler allvarliga komplikationer under första levnadsveckan oavsett förlossningssätt Ökad risk för postpartum infektion Färre som ammar