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Obesità, magrezza e malattie croniche

Sovrappeso BMI 25-29,9 Obesità – BMI ≥30 Corso sul Counseling Preconcezionale Pacchetto formativo completo Raccomandazione Controllare il BMI in tutte le donne regolarmente Informare sui rischi per la salute personale e riproduttivi associati al sovrappeso e all’obesità, compresa la subfertilità Incoraggiare l’ottenimento di un BMI adeguato con alimentazione ed esercizio fisico appropriati, anche ricorrendo a percorsi assistenziali specifici se necessario Perché Il sovrappeso (18-24 anni = 8,3%; 25-44 = 17,5%) e l’obesità (18-24 anni = 1,7%; 25-44 = 4,1%) sono condizioni frequenti e sono associati a vari e non trascurabili rischi per la salute della donna e della prole Il ristabilimento del peso ottimale non può essere ottenuto in gravidanza Commento Le informazioni disponibili sono migliori per l’obesità, il sovrappeso comunque è un fattore di rischio per l’obesità Riferimenti bibliografici Health for all – Italia (2008, dati 2005) Hammoud AO, Gibson M, Peterson CM et al. Impact of male obesity on infertility: a critical review of the current literature. Fertil Steril. 2008;9:897-904 Arendas K, Qiu Q, Gruslin A. Obesity in pregnancy: pre-conceptional to postpartum consequences. J Obstet Gynaecol Can. 2008;30:477-88 Dixit A, Girling JC. Obesity and pregnancy. J Obstet Gynaecol. 2008;28:14-23 Guelinckx I, Devlieger R, Beckers K, Vansant G. Maternal obesity: pregnancy complications, gestational weight gain and nutrition. Obes Rev. 2008;9:140-50 Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril. 2008;90:714-26 Una metanalisi di 16 studi evidenzia che le donne con un BMI>25 kg/m2 hanno un aumentato rischio di morte fetale prima delle 20 settimane (OR 1.67;IC 95%: 1.25-2.25), indipendentemente dal metodo di concepimento. Se si analizza il sottogruppo delle gravidanze indotte (pochi studi) tale rischio sembrerebbe aumentare in quelle con induzione dell’ovulazione. Chu SY, Kim SY, Lau J et al. Maternal obesity and risk of stillbirth: a metaanalysis. Am J Obstet Gynecol. 2007;197:223-8 Una metanalisi (6 studi di coorte e 3 studi caso-controllo) evidenzia un aumentato rischio di natimortalità nelle donne con sovrappeso (BMI 25-29.9 kg/m2): OR 1.47 (IC 95%:1.08-1.94) e in quelle obese (BMI 30 kg/m2) con OR 2.07(IC 95%: 1.59-2.74) Se si analizzano i soli studi di coorte non si osserva significatività statistica per le donne con sovrappeso mentre la stessa persiste per le donne obese (OR 2.04; IC95%:1.30-3.17). Non è chiaro il meccanismo patogenetico che sta alla base dell’associazione anche se è necessario tenere conto dell’aumentata incidenza di diabete mellito e disordini ipertensivi associata alle due condizioni in studio. L’associazione non è completamente spiegata da queste due condizioni e interessa anche la frazione di natimortalità “non spiegata” (unexplained). Pasquali R, Patton L, Gambineri A. Obesity and infertility. Curr Opin Endocrinol Diabetes Obes. 2007;14:482-7 Nelson SM, Fleming RF..The preconceptual contraception paradigm: obesity and infertility. Hum Reprod. 2007;22:912-5 Balen AH, Rutherford AJ. Managing anovulatory infertility and polycystic ovary syndrome. BMJ. 2007;335:663-6 Waller DK et al. Prepregnancy obesity as a risk factor for structural birth defects. Arch Pediatr Adolesc Med 2007; 161:745-750 Lo studio caso-controllo è relativo a 10.249 casi (30 categorie di difetti strutturali) e 4065 controlli) arruolati nel periodo 1997-2002 nell’ambito del National Birth Defects Prevention Study (in 8 stati USA). La madri di nati con spina bifida, difetti cardiaci, atresia anorettale, ipospadia, difetti in riduzione degli arti, ernia diaframmatica e onfalocele avevano una maggiore frequenza di obesità (BMI 30 kg/m2) rispetto ai controlli, con valori di odds ratio compresi tra 1.33 e 2.10. I nati affetti da gastroschisi sono viceversa più frequenti nel gruppo dei controlli. Per 3 condizioni: cardiopatie congenite, ipospadia e onfalocele si osserva un odds ratio significativo anche rispetto al sovrappeso materno (BMI 25.0-29.9 kg/m2). Rispetto a precedenti studi i risultati della ricerca: confermano l’aumentato rischio rispetto a spina bifida, cardiopatie,palatoschisi e una riduzione del rischio per gastroschisi, evidenzia, per la prima volta, un aumentato rischio per atresia anorettale, ipospadia, difetti in riduzione degli arti, ernia diaframmatica e omfalocele non conferma un aumento del rischio rispetto a labioschisi, anencefalia e idrocefalia Boomsma CM, Eijkemans MJ, Hughes EG, et al,. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update. 2006;12:673-83 Catalano PM, Ehrenberg HM. The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG 2006;113:1126-33 Public affairs Committe of the Teratology Society. Teratology public affairs committee position paper: maternal obesity and pregnancy. Birth Defects Res (Part A) 2006; 76:73-77 Yu CK, Teoh TG, Robinson S. Obesity in pregnancy. BJOG. 2006;113:1117-25. Ramachenderan J, Bradford J, McLean M. Maternal obesity and pregnancy complications: a review. Aust N Z J Obstet Gynaecol 2008;48:228-35 Smith SA, Hulsey T, Goodnight W. Effects of obesity on pregnancy. J Obstet Gynecol Neonatal Nurs. 2008;37:176-84 Viswanathan McTigue KM, Harris R, Hemphill B, Lux L, Sutton S, Bunton AJ, Lohr KN. Screening and interventions for obesity in adults: summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003 Dec 2;139(11):933-49. Revisione sistematica per valutare efficacia screening e trattamento obesità nell’adulto DATA SYNTHESIS: No trials evaluated mass screening for obesity, so the authors evaluated indirect evidence for efficacy. Pharmacotherapy or counseling interventions produced modest (generally 3 to 5 kg) weight loss over at least 6 or 12 months, respectively. Counseling was most effective when intensive and combined with behavioral therapy. Maintenance strategies helped retain weight loss. Selected surgical patients lost substantial weight (10 to 159 kg over 1 to 5 years). Weight reduction improved blood pressure, lipid levels, and glucose metabolism and decreased diabetes incidence. The internal validity of the treatment trials was fair to good, and external validity was limited by the minimal ethnic or gender diversity of volunteer participants. No data evaluated counseling harms. Primary adverse drug effects included hypertension with sibutramine (mean increase, 0 mm Hg to 3.5 mm Hg) and gastrointestinal distress with orlistat (1% to 37% of patients). Fewer than 1% (pooled samples) of surgical patients died; up to 25% needed surgery again over 5 years. CONCLUSIONS: Counseling and pharmacotherapy can promote modest sustained weight loss, improving clinical outcomes. Pharmacotherapy appears safe in the short term; long-term safety has not been as strongly established. In selected patients, surgery promotes large amounts of weight loss with rare but sometimes severe complications. Riferimento bibliografico O’Brien TE, Ray JG, Chan WS. Maternal body mass index and the risk of preeclampsia: a systematic overview. Epidemiology 2003;14:368–74 La revisione sistematica comprende 13 studi di coorte (popolazione complessiva reclutata di circa 1.4 milioni di donne): il rischio di pre-eclampsia raddoppia per un incremento dell’indice di massa corporea pre-concezionale dell’ordine di 5-7 Kg/m2. Tale relazione persiste anche negli studi che escludono le donne con ipertensione cronica e diabete mellito, dopo aggiustamento per altri fattori di confondimento. L’obesità, la resistenza all’insulina e l’ipertrigliceridemia sono importanti cofattori nel determinarsi della disfunzione endoteliale. Questa, riducendo la secrezione di prostacicline e aumentando la produzione di perossidasi, comporta vasocostrizione e aggregazione piastrinica, assume un ruolo centrale nello sviluppo della pre-eclampsia International Centre on Birth Defects www.icbd.org

Magrezza BMI ≤ 18,5 Raccomandazione Perché Corso sul Counseling Preconcezionale Pacchetto formativo completo Raccomandazione Controllare il BMI in tutte le donne regolarmente Informare sui rischi per la salute personale e riproduttivi associati alla magrezza, compresa la subfertilità Incoraggiare l’ottenimento di un BMI adeguato Valutare eventuale presenza di anoressia nervosa Perché La magrezza è associata a deficit alimentari, irregolarità del ritmo cardiaco, osteoporosi, amenorrea e subfertilità Prematurità e gastroschisi (RR=3) sono più frequenti nelle gravidanze di donne magre Il ristabilimento del peso ottimale non può essere ottenuto in gravidanza Riferimenti bibliografici Lam PK, Torfs CP. Interaction between maternal smoking and malnutrition in infant risk of gastroschisis. Birth Defects Res A Clin Mol Teratol. 2006 Mar;76(3):182-6. BACKGROUND: Gastroschisis is a severe birth defect characterized by a tear in the infant's abdominal wall. Young mothers have the highest risk of having an infant with gastroschisis. In an animal model, the defect resulted from exposure of pregnant mice to carbon monoxide (CO) in combination with a low protein and low zinc diet. METHODS: We evaluated this model in a study of 55 infants with gastroschisis and 94 age-matched controls that included maternal interview with a food frequency questionnaire. Smoking cigarettes (> or = 1 pack/day) or marijuana (more than once) 3 months prior to pregnancy indicated CO exposure. Low protein or zinc intake and a low body mass index (BMI) indicated maternal malnutrition. RESULTS: When assessed separately, high CO, low protein, low zinc, and low BMI were each significantly associated with an increased risk of gastroschisis. Although we observed significant CO-BMI and CO-zinc interactions after adjusting for income, only a combination of high CO exposure and low BMI yielded a synergistic adverse effect. Compared to the low risk of having an infant with gastroschisis for mothers who did not have low BMI and did not smoke, the risk of having an infant with gastroschisis was 16.3 times (95% CI, 2.49-113.4) higher for mothers who did not have low BMI but smoked, and 19.7 times (95% CI, 4.33-89.6) higher for mothers who did not smoke but had low BMI. However, the risk was 26.5 times (95% CI, 7.85-89.4) higher for mothers who had low BMI and smoked. CONCLUSIONS: Our results suggest that young mothers are at increased risk of having an infant with gastroschisis if they smoke and are also malnourished. Dietz PM, Callaghan WM, Cogswell ME, Morrow B, Ferre C, Schieve LA. Combined effects of prepregnancy body mass index and weight gain during pregnancy on the risk of preterm delivery. Epidemiology. 2006 Mar;17(2):170-7. BACKGROUND: The association between excessive gestational weight gain and preterm delivery is unclear, as is the association between low gestational weight gain and preterm delivery among overweight and obese women. METHODS: Using data from the Pregnancy Risk Assessment Monitoring System in 21 states, we estimated the risk of very (20-31 weeks) and moderately (32-36 weeks) preterm delivery associated with a combination of prepregnancy body mass index (BMI) and gestational weight gain among 113,019 women who delivered a singleton infant during 1996-2001. We categorized average weight gain (kilograms per week) as very low (<0.12), low (0.12-0.22), moderate (0.23-0.68), high (0.69-0.79), or very high (>0.79). We categorized prepregnancy BMI (kg/m) as underweight (<19.8), normal (19.8-26.0), overweight (26.1-28.9), obese (29.0-34.9), or very obese (>or=35.0). We examined associations for all women and for all women with no complications adjusting for covariates. RESULTS: There was a strong association between very low weight gain and very preterm delivery that varied by prepregnancy BMI, with the strongest association among underweight women (adjusted odds ratio = 9.8; 95% confidence interval = 7.0-13.8) and the weakest among very obese women (2.3; 1.8-3.1). Very low weight gain was not associated with moderately preterm delivery for overweight or obese women. Women with very high weight gain had approximately twice the odds of very preterm delivery, regardless of prepregnancy BMI. CONCLUSIONS: This study supports concerns about very low weight gain during pregnancy, even among overweight and obese women, and also suggests that high weight gain, regardless of prepregnancy BMI, deserves further investigation Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associated with underweight, overweight, and obesity. JAMA. 2005 Apr 20;293(15):1861-7. CONTEXT: As the prevalence of obesity increases in the United States, concern over the association of body weight with excess mortality has also increased. OBJECTIVE: To estimate deaths associated with underweight (body mass index [BMI] <18.5), overweight (BMI 25 to <30), and obesity (BMI > or =30) in the United States in 2000. DESIGN, SETTING, AND PARTICIPANTS: We estimated relative risks of mortality associated with different levels of BMI (calculated as weight in kilograms divided by the square of height in meters) from the nationally representative National Health and Nutrition Examination Survey (NHANES) I (1971-1975) and NHANES II (1976-1980), with follow-up through 1992, and from NHANES III (1988-1994), with follow-up through 2000. These relative risks were applied to the distribution of BMI and other covariates from NHANES 1999-2002 to estimate attributable fractions and number of excess deaths, adjusted for confounding factors and for effect modification by age. MAIN OUTCOME MEASURES: Number of excess deaths in 2000 associated with given BMI levels. RESULTS: Relative to the normal weight category (BMI 18.5 to <25), obesity (BMI > or =30) was associated with 111,909 excess deaths (95% confidence interval [CI], 53,754-170,064) and underweight with 33,746 excess deaths (95% CI, 15,726-51,766). Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161,223 to -10,966). The relative risks of mortality associated with obesity were lower in NHANES II and NHANES III than in NHANES I. CONCLUSIONS: Underweight and obesity, particularly higher levels of obesity, were associated with increased mortality relative to the normal weight category. The impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. These findings are consistent with the increases in life expectancy in the United States and the declining mortality rates from ischemic heart disease. Begum F, Buckshe K, Pande JN. Risk factors associated with preterm labour. Bangladesh Med Res Counc Bull. 2003 Aug;29(2):59-66. A Prospective case control study was conducted in a tertiary hospital in Northern India to determine the risk factors associated with preterm labour. Ninety four consecutive patients with preterm spontaneous labour were selected as cases and 188 patients with term spontaneous labour as control. The incidence of preterm labour was found to be 23.3%. The cases were older, shorter and lighter than controls. They had lower body mass index (BMI) and mid arm circumference (MAC). They belonged to significantly lower income group and their educational status was lower. Mean pregnancy order was higher and mean parity was lower amongst the cases. Mean birth weight and apgar score of the babies were lower. Maternal weight <45 kg (OR 4.9), height <150 cm (OR 3.4), BMI <19 kg/m2 (OR 2.91), MAC <20 cm (OR 7.78), education <5 year (OR 2.73), income <2000 rupees (OR 5.05) and birth interval <12 months (OR 6.39) were significant risk factors for preterm labour. Lam PK, Torfs CP, Brand RJ. A low pregnancy body mass index is a risk factor for an offspring with gastroschisis. Epidemiology. 1999 Nov;10(6):717-21. A mother's prepregnancy obesity has been suggested as a risk factor for having offspring with an abdominal wall defect. We evaluated this hypothesis among 104 cases of gastroschisis--a severe birth defect of the abdominal wall most prevalent in infants of young women--and 220 controls with no defect. Using Quetelet's index (QI = weight in kg/height in m2) as a measure of body mass, we found a higher risk of gastroschisis (odds ratio (OR) = 3.2; 95% confidence interval (CI) = 1.4-7.3) for underweight mothers (QI<18.1 kg/m2) and a lower risk (OR = 0.2; 0.05-0.9) for overweight mothers (QI>28.3 kg/m2) as compared with mothers of normal weight. As QI was correlated to height, with the correlation varying according to mother's ethnicity and age, we adjusted for these factors in the analysis; the adjusted values approximated the unadjusted values. Evaluation of QI as a continuous variable showed that, for every unit increase in QI, the risk for gastroschisis decreased by about 11%. Sociodemographic, pregnancy, and nutrient factors did not confound the association. These results suggest that low prepregnancy body mass rather than obesity is a risk factor for gastroschisis. International Centre on Birth Defects www.icbd.org 4

Malattie croniche Corso sul Counseling Preconcezionale Pacchetto formativo completo Tutte le donne con una malattia cronica devono essere informate su: i rischi, per se stesse in gravidanza e per la prole, associati alla malattia possibilità di minimizzare o azzerare i rischi aggiuntivi con il trattamento più idoneo in vista di una gravidanza sulle modalità di programmazione della gravidanza In tutte le donne con una malattia cronica deve essere attuata una terapia compatibile con la gravidanza anche se non programmata International Centre on Birth Defects www.icbd.org 5

Diabete pre-gestazionale Corso sul Counseling Preconcezionale Pacchetto formativo completo Raccomandazione Tutte le donne in età fertile con diabete devono essere incoraggiate a pianificare la gravidanza, a gestire in modo ottimale la malattia e assumere 4-5 mg/die di acido folico Le donne che desiderano una gravidanza devono tenere sotto stretto controllo la glicemia e controllare periodicamente l’HbA1c (obiettivo = 6.1%) Perché Il corretto controllo della glicemia (valutata con dosaggio HbA1c) prima del concepimento riduce il rischio di malformazioni e di altri esiti avversi della gravidanza ai livelli di quelli delle donne non diabetiche Commento La gestione corretta del diabete prima della gravidanza comprende: ottimizzare il controllo della glicemia mantenere un peso corporeo ottimale seguire un regolare programma di esercizio fisico escludere dalle proprie abitudini fumo e alcol valutare le eventuali complicanze vascolari modificare il trattamento farmacologico in vista della gravidanza (es.: ACE-inibitori e statine) ottenere un supporto psico-sociale se necessario Riferimento bibliografico Allen VM, et al. Teratogenicity associated with pre-existing and gestational diabetes. J Obstet Gynaecol Can. 2007;29:927-44 National Collaborating Centre for Womens’s and Children’Health. Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guideline – March 2008 - Funded to produce guidelines for the NHS by NICE American Diabetes Association. Preconception care of women with diabetes. Diabetes Care. 2004 Jan;27 Suppl 1:S76-8. Guideline Development Group. Management of diabetes from preconception to the postnatal period: summary of NICE guidance BMJ. 2008 Mar 29;336(7646):714-7. International Centre on Birth Defects www.icbd.org

Ipo e iper-tiroidismo Raccomandazione Perché Corso sul Counseling Preconcezionale Pacchetto formativo completo Raccomandazione Informare le donne con patologie tiroidee pregresse, in atto o sospette dei rischi riproduttivi e sulla necessità di instaurare il trattamento ottimale in vista della gravidanza Perché L’ipertiroidismo (2/1.000 gravidanze) aumenta il rischio di esiti avversi della gravidanza (EAG) nella madre e di patologie neonatali. I rischi sono correlati al controllo della malattia. L’ipotiroidismo manifesto (2,5% gravidanze) è associato a EAG, basso peso neonatale e disabilità cognitive nella prole L’ipotiroidismo subclinico (2-5% gravidanze) a EAG, basso peso neonatale e alterato sviluppo psicomotorio nella prole Commento Gli esiti avversi della gravidanza nell’ipertiroidismo sono: pre-eclampsia, scompenso cardiaco, crisi tiroidee, distacco placenta; le patologie neonatali nell’ipertiroidismo sono: basso peso neoanatale, natimortalità, ipo-ipertiroidismo immuno-mediato. Gli esiti avversi della gravidanza nell’ipotiroidismo sono: pre-eclampsia, ipertensione, distacco placenta, anemia, emorragie. Riferimenti bibliografici Muller AF, Berghout A, Wiersinga WM, Kooy A, Smits JW, Hermus AR; working group Thyroid Function Disorders of the Netherlands Association of Internal Medicine. Thyroid function disorders--Guidelines of the Netherlands Association of Internal Medicine. Neth J Med. 2008 Mar;66(3):134-42. Thyroid function disorders are common with a female to male ratio of 4 to 1. In adult women primary hypothyroidism and thyrotoxicosis have a prevalence of 3.5/1000 and 0.8/1000, respectively. This guideline is aimed at secondary care providers especially internists, but also contains relevant information for interested general practitioners and gynaecologists. A multidisciplinary working group, containing delegates of professional and patient organisations, prepared the guideline. According to principles of 'evidence-based medicine' available literature was studied and discussed. Considering the availability and quality of published studies a practical advice was formulated. For a full overview of the literature and considerations the reader is referred to the original version of the guideline (accessible through NIV-net). In this manuscript we have aimed to provide the practicing internist with practical and 'as evidence-based as possible' treatment guidelines with respect to thyroid function disorders. Cleary-Goldman J, Malone FD, Lambert-Messerlian G, Sullivan L, Canick J, Porter TF, Luthy D, Gross S, Bianchi DW, D'Alton ME. Maternal thyroid hypofunction and pregnancy outcome. Obstet Gynecol. 2008 Jul;112(1):85-92. Casey BM, Dashe JS, Wells CE, McIntire DD, Leveno KJ, Cunningham FG. Subclinical hyperthyroidism and pregnancy outcomes. Obstet Gynecol. 2006 Feb;107(2 Pt 1):337-41. OBJECTIVE: Subclinical hyperthyroidism has long-term sequelae that include osteoporosis, cardiovascular morbidity, and progression to overt thyrotoxicosis or thyroid failure. The objective of this study was to evaluate pregnancy outcomes in women with suppressed thyroid-stimulating hormone (TSH) and normal free thyroxine (fT(4)) levels. METHODS: All women who presented to Parkland Hospital for prenatal care between November 1, 2000, and April 14, 2003, underwent thyroid screening by chemiluminescent TSH assay. Women with TSH values at or below the 2.5th percentile for gestational age and whose serum fT(4) levels were 1.75 ng/dL or less were identified to have subclinical hyperthyroidism. Those women screened and delivered of a singleton infant weighing 500 g or more were analyzed. Pregnancy outcomes in women identified with subclinical hyperthyroidism were compared with those in women whose TSH values were between the 5th and 95th percentiles. RESULTS: A total of 25,765 women underwent thyroid screening and were delivered of singleton infants. Of these, 433 (1.7%) were considered to have subclinical hyperthyroidism, which occurred more frequently in African-American and/or parous women. Pregnancies in women with subclinical hyperthyroidism were less likely to be complicated by hypertension (adjusted odds ratio 0.66, 95% confidence interval 0.44-0.98). All other pregnancy complications and perinatal morbidity or mortality were not increased in women with subclinical hyperthyroidism. CONCLUSION: Subclinical hyperthyroidism is not associated with adverse pregnancy outcomes. Our results indicate that identification of subclinical hyperthyroidism and treatment during pregnancy is unwarranted. LEVEL OF EVIDENCE: II-2. Mestman JH. Hyperthyroidism in pregnancy. Best Pract Res Clin Endocrinol Metab. 2004 Jun;18(2):267-88. Review. Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol (Oxf). 2003 Sep;59(3):282-8. Free full text Women with antibodies against the enzyme thyroid peroxidase [TPO-Ab; formerly microsomal antibodies (MsAb)] are at particular risk for developing postpartum thyroid dysfunction; the latter is significantly associated with postpartum depression. Although the negative effect of postpartum maternal depression on child development is well documented, the consequences of elevated titers of TPO-Ab during pregnancy and subsequent postpartum thyroid dysfunction on child development are not known. In a prospective study of a cohort of 293 pregnant women, the occurrence of TPO-Ab during gestation, thyroid dysfunction, and depression was investigated. Five years after delivery, child development was assessed in 230 children of the original cohort using the Dutch translation of the McCarthy Scales of Children's Abilities. Children of women with TPO-Ab during late gestation (n = 19, with normal thyroid function) had significantly lower scores (by t test) on the McCarthy Scales of Children's Abilities than antibody-negative women. The difference on the General Cognitive Scale, which reflects IQ scores, was substantial (10.5 points; t = 2.8; P = 0.005). After correction for possibly confounding variables, maternal TPO-Ab during gestation was found to be the most important factor related to the scores on the General Cognitive Scale (odds ratio = 10.5; 95% confidence interval = 3-34; P = 0.003). We conclude that children of pregnant women who had elevated titers of TPO-Ab but normal thyroid function are at risk for impaired development American College of Obstetricians and Gynecologists.. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 37, August 2002. (Replaces Practice Bulletin Number 32, November 2001). Thyroid disease in pregnancy. Obstet Gynecol. 2002 Aug;100(2):387-96. Because thyroid disease is the second most common endocrine disease affecting women of reproductive age, obstetricians often care for patients who have been previously diagnosed with alterations in thyroid gland function. In addition, both hyperthyroidism and hypothyroidism may initially manifest during pregnancy. Obstetric conditions, such as gestational trophoblastic disease or hyperemesis gravidarum, may themselves affect thyroid gland function. This document will review the thyroid-related pathophysiologic changes created by pregnancy and the maternal-fetal impact of thyroid disease. Allan WC, Haddow JE, Palomaki GE, Williams JR, Mitchell ML, Hermos RJ, Faix JD, Klein RZ. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen. 2000;7(3):127-30. Free Full Text Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, O'Heir CE, Mitchell ML, Hermos RJ, Waisbren SE, Faix JD, Klein RZ. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999 Aug 19;341(8):549-55. Free Full Text Mestman JH. Hyperthyroidism in pregnancy. Clin Obstet Gynecol. 1997 Mar;40(1):45-64. Review. The prevalence of hyperthyroidism in pregnancy is about 0.2%. The most common cause is Graves' disease. Maternal, fetal, and neonatal morbidity and mortality may be reduced to a minimum with careful attention to the clinical symptoms and interpretation of thyroid tests. Ideally, hyperthyroid women should be rendered euthyroid before considering conception. The incidence of maternal and neonatal morbidity is significantly higher in those patients whose hyperthyroidism is not medically controlled. Even the incidence of thyroid storm is high in women who are under poor medical supervision in the presence of a medical or obstetric complication. Maternal morbidity includes a higher incidence of toxemia, premature delivery, placenta abruptio, congestive heart failure, and thyroid crisis. In some series, anemia and infections were also reported. Neonatal morbidity includes SGA neonates, intrauterine growth retardation, LBW infants, and prematurity. Fetal goiter and transient neonatal hypothyroidism is occasionally reported in infants of mothers who have been overtreated with ATD. Propylthiouracil and MMI are equally effective in controlling the disease. In most patients, symptoms improved and thyroid tests returned to normal in 3-8 weeks after initiation of therapy. Resistance to ATD is extremely rare, most cases are caused by patient poor compliance. Surgery for the treatment of hyperthyroidism is reserved for the unusual patient who is allergic to both ATD; to those who have large goiters; to those who require large doses of ATD; or to those patients who poorly comply. Fetal and neonatal hyperthyroidism can be predicted in the majority of cases by the previous maternal medical and obstetric history and by the proper interpretation of thyroid tests. Finally, hyperthyroidism may recur in the postpartum period. Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JH. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol. 1993 Mar;81(3):349-53. Davis LE, Leveno KJ, Cunningham FG. Hypothyroidism complicating pregnancy. Obstet Gynecol. 1988 Jul;72(1):108-12. International Centre on Birth Defects www.icbd.org 7

Precedenti gravidanze e malattie genetiche

Precedenti gravidanze Raccomandazione Vvalutare la storia riproduttiva della donna Se la donna ha avuto 2 o più aborti spontanei, oppure un parto prematuro, un neonato con restrizione della crescita fetale, un nato morto, o un parto cesareo, Prendere adeguati provvedimenti per identificare la possibile causa e individuare l’eventuale trattamento Fornire indicazioni sul rischio di ricorrenza dell’evento Perché Alcune cause di precedenti esiti avversi della riproduzione possono essere affrontate con adeguati trattamenti o suggerire la necessità di una consulenza genetica

Malattie genetiche Raccomandazione Perché Identificare attraverso l’anamnesi personale e familiare i fattori di rischio per malattie genetiche Raccomandare una consulenza con uno specialista in genetica medica, se necessario o in caso di dubbio Prescrivere lo screening per emoglobinopatie in presenza di indici anormali all’emocromo Informare anticipatamente la coppia sugli screening prenatali per la sindrome di Down e per le malformazioni Informare sullo screening per la fibrosi cistica Perché La coppia informata correttamente prima della gravidanza può prendere decisioni sul proprio futuro riproduttivo in maggiore autonomia e con minore ansietà

Vaccinazione, trattamento o prevenzione delle infezioni più comuni

Varicella Raccomandazione Perché Durante il counseling preconcezionale valutare in tutte le donne lo stato immunitario nei confronti della varicella attraverso anamnesi vaccinale, oppure avvenuta infezione diagnosticata da un medico, oppure test immunologico Vaccinare le donne che non risultano immuni Perché La varicella in gravidanza può provocare: nella donna: polmonite (16%) con elevata mortalità materna (28%) una specifica embriopatia (infezione < 20 settimane di gestazione) zoster precoce dopo la nascita (infezione > 20 settimane) varicella congenita del neonato (infezione <3 settimane dal parto)

Rosolia Raccomandazione Perché Durante il counseling preconcezionale valutare in tutte le donne lo stato immunitario nei confronti della rosolia attraverso anamnesi vaccinale, oppure avvenuta infezione diagnosticata da un medico, oppure test immunologico Vaccinare le donne che non risultano immuni Perché La rosolia in gravidanza può provocare una specifica embriopatia

Alimentazione folati, acido folico altre vitamine ed oligoelementi

Folati, acido folico e altre vitamine B Raccomandazione Se la donna / coppia non esclude la possibilità di una gravidanza nei prossimi mesi: suggerire un’alimentazione ricca di frutta e verdura, e … poiché l’alimentazione da sola, seppure ricca di folati non raggiunge livelli ottimali prescrivere fino alla fine del 3° mese di gravidanza un prodotto che fornisca almeno 0,4 mg/die di acido folico oppure un polivitaminico con acido folico ma senza vitamina A

Assumere più acido folico A tutte le donne che eseguono un counseling preconcezionale è utile: raccomandare di scegliere un’alimentazione ricca di frutta (es. arance, mandarini, clementine, succhi freschi di agrumi) e verdura fresca (es. spinaci, carciofi, indivia, bieta, broccoli, cavoli, fagioli) e di utilizzare alimenti arricchiti con acido folico prescrivere un supplemento vitaminico a base di acido folico (0,4 mg al giorno) senza vitamina A preformata Il SSN ha inserito in fascia A prodotti a base di acido folico (0,4 mg/cp), con la precisa indicazione: “profilassi primaria dei difetti dello sviluppo del tubo neurale in donne in età fertile, che stanno pianificando una gravidanza” E’ fondamentale che questa raccomandazione venga seguita anche per tutto il primo trimestre di gravidanza

Assumere più acido folico Donne con aumentato rischio di DTN o altre malformazioni Tutte le donne che hanno avuto una gravidanza esitata in una interruzione dopo diagnosi prenatale o in un nato con un DTN devono assumere un supplemento di acido folico al dosaggio di 5 mg al giorno Inoltre, sulla base di una serie di considerazioni, è utile che il dosaggio di 5 mg al giorno venga prescritto anche alle donne che: hanno o hanno avuto un familiare (nella propria famiglia o nella famiglia del partner) con un DTN sono affette da epilessia, anche se non in trattamento con farmaci anticonvulsivanti (vedi anche sezione 2.8.3 epilessia) hanno avuto una gravidanza esitata in una interruzione dopo diagnosi prenatale o in un nato con una qualunque malformazione congenita sono affette da diabete sono affette da obesità assumono, o hanno assunto in precedenza, quantità eccessive di bevande alcoliche

Fumo, bevande alcoliche, farmaci e agenti ambientali

Fumo di sigaretta Raccomandazione Perché Tutte le donne in età fertile che fumano vanno incoraggiate a smettere di fumare, soprattutto in vista di una gravidanza, attraverso una breve sessione di counseling adeguato oppure consigliando un intervento presso centri specialistici. Perché Il fumo è un fattore di rischio per lo stato di salute in generale e per molteplici esiti avversi della riproduzione tra cui restrizione dell’accrescimento fetale, le schisi orali e la SIDS.

Bevande alcoliche Raccomandazione Indagare in tutte le donne in età fertile sull’abitudine ad assumere bevande alcoliche Se la donna ne fa un uso moderato informare sull’opportunità dell’astensione pressochè completa in vista della gravidanza e in gravidanza, e sui rischi dello stato di ebbrezza (binge drinking) Se la donna è una forte bevitrice informare sui rischi legati all’abuso di bevande alcoliche per la salute riproduttiva e per lo sviluppo embrio-fetale ed aiutarla a smettere e a rimandare la gravidanza

Crediti FNCO Ultima versione 3 gennaio 2008 Uno o più rappresentanti delle seguenti organizzazioni hanno condiviso e/o suggerito modifiche: ACP, AGICo, AGEO, AGUI, AOGOI, APEL, CFC, CIPE, FIMP, FIOG, FNCO, ONSP, SaPeRiDoc, SIEOG, SIGO, SIMG, SIMGePeD, SIN, SIGU FNCO SIN Ultima versione 3 gennaio 2008

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