Altre malattie croniche

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1 Altre malattie croniche
Diapositive rivedute e corrette il 15 Settembre 2010

2 Raccomandazione generale
Identificare le donne con una malattia cronica (Ri-) valutarne il trattamento e mantenere/instaurarquello che presenta maggiori vantaggi per la donna e minori rischi per lo sviluppo embrio- fetale. Se necessario in collaborazione con lo specialista. Se sono necessari modifiche di trattamento: fornire indicazioni sul controllo della fertilità finché non è stata valutata l’efficacia del nuovo trattamento. Perché Uno stato di salute ottimale, pur nei limiti imposti dalla presenza di una malattia cronica, garantisce una gravidanza più sicura e minimizza i rischi per il nascituro.

3 Alcune specifiche malattie croniche

4 Epilessia Raccomandazione Perché
Corso sul Counseling Preconcezionale Pacchetto formativo completo Raccomandazione In tutte le donne in età fertile con epilessia in trattamento con un qualsiasi farmaco anti-epilettico (FAE) , in vista di una gravidanza è necessario: rivalutare la necessità e l’appropriatezza del trattamento in atto per: sospendere il trattamento, instaurare una monoterapia se necessario e possibile, ridurre/frazionare il dosaggio di un FAE, soprattutto valproato escludere il valproato se possibile; informare sul rischio di fallimento di metodi contraccettivi ormonali associato ad alcuni FAE, prescrivere acido folico 4-5 mg/die. Perché I FAE aumentano il rischio di malformazioni (RR=2-3), e probabilmente anche di altri esiti avversi della riproduzione compresa una ridotta capacità cognitiva del bambino quando grandicello associata al valproato. International Centre on Birth Defects 4 4

5 Epilessia, farmaci e gravidanza
Esiti avversi della riproduzione Fertilità ridotta Aborto spontaneo Prematurità Restrizione crescita fetale Parto cesareo Malformazioni Disturbi cognitivi del bambino più grande Ricorrenza della patologia epilettica La frequenza delle crisi in gravidanza Aumenta nel 17% dei casi Rimane invariato nel 67% dei casi Diminuisce nel 16 % Rischio per un genitore di avere un figlio con epilessia = 4,2 % (variabile tra 1,7 e 7,3 % in base al tipo di epilessia e agli studi condotti) Commento I vari esiti avversi della riproduzione associati ad epilessia materna in trattamento con farmaci antiepilettici (es.: fertilità ridotta, aborto spontaneo, prematurità, mortalità perinatale e neonatale, disturbi cognitivi del bambino più grande), eccetto le malformazioni, vengono riferiti in modo incostante nelle varie indagini eseguite fino ad oggi e in questa sede vanno tenuti presenti come indicazione di cautela, senza poter fornire l’incremento di rischio. La frequenza delle crisi in gravidanza, aumenta nel 17% dei casi, rimane invariato nel 67% dei casi, diminuisce nel 16 %. Il rischio per una donna con epilessia di avere un figlio affetto da epilessia è variabile tra l’1,7 e il 7,3% (mediana 4,2%) e dipende dal tipo di epilessia (Tsuboi 1989, citato nel testo Medical Genetics di Emery e Rimoin). Ovviamente lo stesso rischio si verifica se il padre è affetto. Il rischio aumenta se uno dei precedenti figli è affetto. Il rischio di malformazioni verrà affrontato nel dettaglio nelle prossime diapositive. Riferimenti bibliografici Harden CL, Hopp J, Ting TY, Pennell PB, French JA, Allen Hauser W, Wiebe S, Gronseth GS, Thurman D, Meador KJ, Koppel BS, Kaplan PW, Robinson JN, Gidal B, Hovinga CA, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Le Guen C; American Academy of Neurology; American Epilepsy Society. Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): I. Obstetrical complications and change in seizure frequency: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia May;50(5): Review. Disponibile su richiesta Pennell PB. EURAP Outcomes for Seizure Control During Pregnancy: Useful and Encouraging Data. Epilepsy Curr Nov-Dec;6(6): Free Full Text EURAP Study Group. Seizure control and treatment in pregnancy: observations from the EURAP epilepsy pregnancy registry. Neurology Feb 14;66(3): Kälviäinen R, Tomson T. Optimizing treatment of epilepsy during pregnancy. Neurology Dec 26;67(12 Suppl 4):S Review. Disponibile su richiesta Crawford P. Best practice guidelines for the management of women with epilepsy. Epilepsia. 2005;46 Suppl 9: Disponibile su richiesta 5

6 Epilessia, farmaci e malformazioni
Corso sul Counseling Preconcezionale Pacchetto formativo completo L’epilessia è una malattia molto eterogenea, la necessità di un trattamento farmacologico (si/no e tipo di farmaco/i) è molto variabile; dipende anche da “abitudini” della classe medica dei vari paesi Il rischio di malformazioni associato ai farmaci dipende dal tipo di regime terapeutico (> politerapia) e dal tipo di farmaci (> valproato e fenitoina). In generale RR = 2,0-3,0 (Incidenza = 4-10% vs 2-3%). Scarse le informazioni sui nuovi anti-epilettici L’epilessia di per se stessa, non in trattamento, non sembra essere associata ad aumentato rischio di malformazioni Commento Di per sé l’epilessia non sembra essere associata ad un rischio più elevato di MC, come indicato da una meta-analisi di studi effettuati in cui è stato valutato anche il bias di pubblicazione (Fried et al., 2004). Gli studi sull’argomento sono tuttavia ancora scarsi e sarebbero necessari ulteriori studi per ottenere un’evidenza più robusta di questa affermazione. L’uso di farmaci anticonvulsivanti di vecchia generazione (es.: trimetadione, fenitoina, fenobarbital, valproato) soprattutto se in politerapia comportano un aumento del rischio di MC gravi di 2-3 volte (6-10% vs 2-3%). Il rischio risulta più elevato per varie malformazioni, in particolare schisi orali, cardiopatie ed ipospadia. Valproato e carbamazepina sono associati ad un rischio più elevato di spina bifida rispettivamente del 2-5% e dello 0,5-1%. Soltanto il valproato presenta un effetto dose (più elevato con dosaggi > mg/die). In monoterapia il farmaco più teratogeno è il valproato, il meno teratogeno il fenobarbital. Gli anticonvulsivanti di vecchia generazione sono associati anche ad rischio aumentato di aborto spontaneo, nati morti, ritardo di crescita intrauterino e dimorfismi minori soprattutto a carico del volto. Questi ultimi, comuni a tutti gli anticonvulsivanti, non predicono tuttavia uno sviluppo psico-motorio ritardato, la cui reale presenza, seppure modesta e limitata a specifiche aree di sviluppo, è ancora in dubbio. Per quanto riguarda i nuovi farmaci anticonvulsivanti i più studiati sono la lamotrigina e l’oxcarbazepina. Ambedue non sembrano associati a rischi più elevati anche se per la lamotrigina cominciano a sorgere dubbi e il dosaggio elevato mostra rischi analoghi ai farmaci di vecchia generazione. Riferimenti bibliografici Meador K, Reynolds MW, Crean S, Fahrbach K, Probst C. Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res Sep;81(1): Review. Free Full Text Tomson T, Hiilesmaa V. Epilepsy in pregnancy. BMJ. 2007; 335: Disponibile su richiesta Artama M, Isojärvi JI, Auvinen A. Antiepileptic drug use and birth rate in patients with epilepsy—a population-based cohort study in Finland. Hum Reprod. 2006; 21: Disponibile su richiesta Kini U, Adab N, Vinten J, Fryer A, et al. Liverpool and Manchester Neurodevelopmental Study Group. Dysmorphic features: an important clue to the diagnosis and severity of fetal anticonvulsant syndromes. Arch Dis Child Fetal Neonatal Ed. 2006; 91: F90-5. Disponibile su richiesta Meador KJ, Baker GA, Finnell RH, Kalayjian LA, et al. NEAD Study Group. In utero antiepileptic drug exposure: fetal death and malformations. Neurology. 2006; 67: Disponibile su richiesta Perucca E. Birth defects after prenatal exposure to antiepileptic drugs. Lancet Neurol. 2005; 4: Fried S, Kozer E, Nulman I, Einarson TR, Koren G. Malformation rates in children of women with untreated epilepsy: a meta-analysis. Drug Saf. 2004;27(3): Disponibile su richiesta International Centre on Birth Defects 6 6

7 Epilessia, farmaci e malformazioni
Corso sul Counseling Preconcezionale Pacchetto formativo completo Farmaco Malformazione Rischio assoluto e RR Tutti Cardiopatie congenite 1 su 70, RR=2 Acido valproico Malformazioni maggiori (tutte) 1 su 13, RR=3 Fenitoina (F-barbital) Labioschisi 1 su 240, RR = 7 Palatoschisi 1 su 740, RR = 3 Spina bifida 1 su 140, RR = 20 Carbamazepina 1 su 280, RR = 10 Ipospadia 1 su 97, RR = 6 Dismorfismi del volto (sindrome) ? ? Ipo-agenesia arti preassiale, altre ? ? ? ? Commento I rischi specifici per le varie malformazioni sono noti solo per alcune di esse, quelle più comunemente associate ai FAE. E’ sempre opportuno ricordare il rischio individuale di base e quindi notare l’incremento di rischio (RR) legato ai FAE. Tutti i FAE possono causare dismorfismi del volto, anche se è più nota la sindrome da fenilidantoina. Riferimenti bibliografici Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK, de Jong-van den Berg LT; EUROCAT Antiepileptic Study Working Group. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med Jun 10;362(23): Disponibile su richiesta Harden CL, Meador KJ, Pennell PB, Hauser WA, Gronseth GS, French JA, Wiebe S, Thurman D, Koppel BS, Kaplan PW, Robinson JN, Hopp J, Ting TY, Gidal B, Hovinga CA, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Hirtz D, Le Guen C; American Academy of Neurology; American Epilepsy Society. Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): II. Teratogenesis and perinatal outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia May;50(5): Review. Disponibile su richiesta Rodríguez-Pinilla E, Mejías C, Prieto-Merino D, Fernández P, Martínez-Frías ML; ECEMC Working Group. Risk of hypospadias in newborn infants exposed to valproic acid during the first trimester of pregnancy: a case-control study in Spain. Drug Saf ;31(6): Disponibile su richiesta BACKGROUND: Hypospadias is one of the most frequently occurring genital anomalies described in infants prenatally exposed to valproic acid (VA). However, to our knowledge, only one publication has studied a potential causal relationship between VA and hypospadias, only estimating the unadjusted global risk. Here we present the results of a multivariate case-control study aimed at analysing and quantifying the specific risk of hypospadias in newborn infants exposed to VA during the first trimester of pregnancy. METHODS: The data analysed here were derived from the Spanish Collaborative Study of Congenital Malformations (ECEMC), an ongoing, hospital-based, case-control study and surveillance system in which collaborating paediatricians identify case and control infants. The paediatricians collect the same data for both case and control infants, blinded to information on any prenatal exposure. The information includes 312 items related to many prenatal exposures, including drug exposure, reproductive and family history, and other characteristics. The sample analysed included 2,393 infants with hypospadias and 12,465 male controls. RESULTS: The results showed that the unadjusted risk of hypospadias in infants prenatally exposed to VA was 5.23 (95% CI 2.31, 11.86; p < ). Once adjusted for 13 potential confounding factors using conditional logistic regression analyses, the value of the risk was of a similar magnitude (odds ratio = 5.71; 95% CI 1.78, 18.36; p = 0.003). In addition, the frequency of hypospadias in the study population was approximately 1.8/1000 births. This allowed us to calculate the specific risk for an infant with hypospadias to be born to an exposed mother, which was 1 child in 97 births to mothers using VA during the first trimester of pregnancy. We consider this information much more useful for risk assessment than the risk value itself. CONCLUSIONS: An alteration of placental gonadotrophic stimulation caused by changes in gonadotropin-releasing hormone release produced by the effects of VA on GABA is a possible pathogenic mechanism. Our results support the relationship between prenatal exposure to VA and hypospadias. Il rischio legato all’acido valproico è dose dipendente International Centre on Birth Defects 7 7

8 Epilessia: raccomandazioni dettagliate
In una paziente con epilessia in trattamento con FAE è indicato pianificare la gravidanza per: sospendere eventualmente la terapia qualora l’epilessia sia considerata guarita oppure le crisi siano tali da non mettere a rischio la madre o la prosecuzione della gravidanza sostituire i farmaci fino ad allora assunti, se a più alto rischio teratogeno come il valproato, con altri per i quali vi siano relative sicurezze d’impiego nel primo trimestre (periodo dell’organogenesi) ridurre il numero dei farmaci utilizzati e cercare di attuare una monoterapia se utilizzato acido valproico o lamotrigina utilizzare il minimo dosaggio possibile Commento Sulla base dei rischi di malformazioni congenite associati ai FAE sono state sviluppare da varie organizzazioni alcune raccomandazioni di buon senso. Tali raccomandazioni tuttavia non sono state ancora validate. In altre parole non esiste la dimostrazione formale che il counseling preconcezionale riduca il rischio di malformazioni o di altri esiti avversi della riproduzione. Sul piano della comunicazione con la donna Sottolineare che: il 90% e più delle gravidanze, che avvengono in donne che hanno l’epilessia ed è in trattamento con FAE, ha un esito del tutto normale. Esiste un rischio aggiuntivo, modesto, legato soprattutto ai FAE, e soprattutto a certe malformazioni, e non alla malattie di per sé, che può essere ridotto seguendo le raccomandazioni indicate in queste due diapositive. ogni valutazione del trattamento va fatta dallo specialistica in epilessia che alcuni rischi malformativi, associati al trattamento con FAE, possono essere individuati durante la gravidanza con ecografie mirate (es.: spina bifida e cardiopatie gravi), anticipare comunque che la sensibilità dell’ecografia non è del 100% Ricordare che: se è necessario variare il regime terapeutico e quindi posticipare il concepimento alcuni FAE (es.: barbiturici, fenitoina, carbamazepina, topiramato, lamotrigina) alterano l’efficacia della contraccezione ormonale. il rischio di avere un figlio affetto da epilessia si aggira intorno 3%. Riferimenti bibliografici Crawford P. Best practice guidelines for the management of women with epilepsy. Epilepsia. 2005;46 Suppl 9: PNLG Regioni 4. Diagnosi e trattamento delle epilessie. Linee guida Consiglio Sanitario Regionale Regione Toscana. Data aggiornamento: 2008 Lega Italiana Contro l’Epilessia (LICE) in collaborazione con AOGOI, SIGO, SIN, SINP, SINPIA, SIP. Conferenza nazionale di consenso su gravidanza, parto, puerperio ed epilessia. SIGO Notizie – Supplemento a Italian Journal Gynecol Obstet 2007, 3: 6-25 AAVV. Farmaci e gravidanza. La valutazione del rischio teratogeno basata su prove di efficacia. Agenzia Italiana del Farmaco – Ministero della Salute, Istituto Poligrafico e Zecca dello Stato – Roma, 2005 8

9 Epilessia: raccomandazioni dettagliate
Nella maggior parte delle pazienti in trattamento con il valproato le possibili alternative in vista di una gravidanza sono: fenobarbital e lamotrigina. Entrambi i farmaci possono interagire con gli steroidi sessuali e il loro uso in gravidanza e durante l’allattamento necessita di attenzione Le variazioni e le sostituzioni della terapia antiepilettica andrebbero completate nell’arco di 6 mesi, assicurandosi che la donna utilizzi un efficace controllo della fertilità Prescrivere 4-5 mg/die di acido folico per prevenire la spina bifida e possibilmente altre malformazioni ed altri esiti avversi della riproduzione (es.: aborto spontaneo) 9

10 Ipo e iper-tiroidismo Ipo e iper-tiroidismo Raccomandazione Perché
Corso sul Counseling Preconcezionale Ipo e iper-tiroidismo Ipo e iper-tiroidismo 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 per ottenere un buono stato di eutiroidismo in vista della gravidanza. Perché L’ipertiroidismo (2/1.000 gravidanze) non ben controllato aumenta il rischio di esiti avversi della riproduzione (EAR*). I rischi sono correlati al controllo della malattia. Preferibile il propiltiouracile al metimazolo. L’ipotiroidismo manifesto (2,5% gravidanze) è associato a EAR* (in particolare basso peso neonatale e disabilità cognitive nella prole). L’ipotiroidismo subclinico (2-5% gravidanze) sembra essere associato a 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 Bánhidy F, Puhó EH, Czeizel AE. Possible association between hyperthyroidism in pregnant women and obstructive congenital abnormalities of urinary tract in their offspring - a population-based case-control study. J Matern Fetal Neonatal Med May 26. [Epub ahead of print] Conclusions. The lack of appropriate treatment of pregnant women affected with hyperthyroidism seems to be the major problem, because it would be necessary to prevent the hyperthyroidism related risks of pregnancy complications and CAs which exceed 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 Mar;66(3): 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 Jul;112(1):85-92. Casey BM, Dashe JS, Wells CE, McIntire DD, Leveno KJ, Cunningham FG. Subclinical hyperthyroidism and pregnancy outcomes. Obstet Gynecol Feb;107(2 Pt 1): Free Full Text 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 ). 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 Jun;18(2): 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) Sep;59(3): 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 (Replaces Practice Bulletin Number 32, November 2001). Thyroid disease in pregnancy. Obstet Gynecol Aug;100(2): 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): 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 Aug 19;341(8): Free Full Text Mestman JH. Hyperthyroidism in pregnancy. Clin Obstet Gynecol Mar;40(1): 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 Mar;81(3): Davis LE, Leveno KJ, Cunningham FG. Hypothyroidism complicating pregnancy. Obstet Gynecol Jul;72(1): * Incrementi di rischio modesti International Centre on Birth Defects 10 10

11 Ipertensione Raccomandazione Perché
Corso sul Counseling Preconcezionale Pacchetto formativo completo Raccomandazione Controllare la pressione arteriosa in tutte le donne ed accertare attraverso l’anamnesi eventuali precedenti ipertensivi. Informare le donne con ipertensione sui rischi riproduttivi ad essa associati e sulla necessità di instaurare il trattamento ottimale in vista della gravidanza sostituendo se necessario gli ACE-inibitori, antagonisti dei recettori dell’angiotensina II e clorotiazide controindicati in gravidanza. Perché L’ipertensione (3% gravidanze) non ben controllata aumenta il rischio di esiti avversi: nella madre: pre-eclampsia (50-75%), eclampsia, distacco di placenta (10-20%), nel neonato: restrizione della crescita intrauterina (25-40%, ipotizzato incremento di ipospadia). I rischi sono correlati al controllo della malattia, grado di ipertensione, insorgenza di pre-eclampsia. Commento Rischi associati all’ipertensione in gravidanza Pre-eclampsia (50-75%); Restrizione crescita fetale (25-40%) Distacco placenta (10-20%) Un recente studio (Caton et al., 2008) ipotizza anche un incremento di rischio di ipospadia (OR=2.1) associato a ipertensione (a prescindere dai farmaci) Riferimenti bibliografici Visintin C, Mugglestone MA, Almerie MQ, Nherera LM, James D, Walkinshaw S; Guideline Development Group. Management of hypertensive disorders during pregnancy: summary of NICE guidance. BMJ Aug 25;341:c2207. Caton AR, Bell EM, Druschel CM, Werler MM, Mitchell AA, Browne ML, McNutt LA, Romitti PA, Olney RS, Correa A; National Birth Defects Prevention Study. Maternal hypertension, antihypertensive medication use, and the risk of severe hypospadias. Birth Defects Res A Clin Mol Teratol Jan;82(1): Disponibile su richiesta Powrie RO. A 30-year-old woman with chronic hypertension trying to conceive. JAMA Oct 3;298(13): Disponibile su richiesta Sibai BM. Caring for women with hypertension in pregnancy. JAMA Oct 3;298(13): Editorial Disponibile su richiesta James PR, Nelson-Piercy C. Management of hypertension before, during, and after pregnancy. Heart Dec;90(12): Free Full Text Waterstone M, Bewley S, Wolfe C. Incidence and predictors of severe obstetric morbidity: case-control study. BMJ May 5;322(7294): ; Free Full Text International Centre on Birth Defects 11 11

12 Quali sono i farmaci di prima scelta in vista della gravidanza ?
Metildopa 250 mg x 2/die fino a 1000 mg x2-3 die. Il farmaco meglio studiato per la gravidanza. Può provocare sonnolenza e vertigini; 20% dei casi non tollerate dosi adeguate. Labetalolo 100 mg x 2/die fino a 800 mg x2-3/die. Diminuisce la PA senza diminuire il flusso uteroplacentare; non aumenta rischio di restrizione fetale come altri beta-bloccanti. Nifedipina 10-40 mg x3/die o equivalente per long-lasting. Riferimenti bibliografici Powrie RO. A 30-year-old woman with chronic hypertension trying to conceive. JAMA Oct 3;298(13): Disponibile su richiesta 12

13 Trombofilie Raccomandazione
Identificare le donne con anamnesi personale o familiare positiva per trombosi delle vene profonde o per aborti ricorrenti e inviarle allo specialista per una diagnosi più precisa. Lo screening delle mutazioni o il dosaggio dell’omocisteina non è indicato né nel periodo preconcezionale né all’inizio della gravidanza. Perché La trombofilia può essere causa di pre-eclampsia, eclampsia e restrizione crescita fetale. Il trattamento con eparina in gravidanza sembra ridurre il rischio degli esiti avversi. Dodd JM, McLeod A, Windrim RC, Kingdom J. Antithrombotic therapy for improving maternal or infant health outcomes in women considered at risk of placental dysfunction. Cochrane Database Syst Rev Jun 16;6:CD AUTHORS' CONCLUSIONS: The review identified no significant differences for the primary outcomes perinatal mortality, preterm birth less than 34 weeks' gestation, and childhood neurodevelopmental handicap, although the number of studies and participants was small. While treatment with heparin appears promising with a reduction in pre-eclampsia, eclampsia, and infant birthweight less than the 10th centile for gestational age, the number of studies and participants included was small, and to date important information about serious adverse infant and long-term childhood outcomes is unavailable. Further research is required. 13

14 Trombofilie Cause Conseguenze Mutazioni genetiche
Fattore V° di Leiden Protrombina – G20210A Iperomocisteinemia (MTHFR – C677T) Deficit di proteina C, S e antitrombina Sindrome antifosfolipidi Conseguenze Trombosi vene profonde in gravidanza Aborto precoce, tardivo o ricorrente Pre-eclampsia Abruptio placenta Restrizione crescita intrauterina Riferimenti bibliografici Wu et al. Screening for thrombophilia in high risk situations. Health Technology Assessment 2006; Vol 10; No 11. 14

15 Iperfenilalaninemia Raccomandazione
Corso sul Counseling Preconcezionale Pacchetto formativo completo Raccomandazione Identificare le donne in età fertile a cui è stata diagnosticata una iperfenilalaninemia in epoca neonatale (1 su circa). Se non desiderano una gravidanza devono adottare un efficace metodo di controllo della fertilità Se desiderano una gravidanza devono essere seguite da uno specialista per ri-adottare un’alimentazione priva o povera di fenilalanina per tutto il periodo preconcezionale e gravidico. Perché L’iperfenilalaninemia è teratogena: cardiopatie, microcefalia, deficit cognitivo, peso neonatale < gr Riferimento bibliografico Albandar JM, Brunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, J Periodontol Jan;70(1):13-29. Marakoglu I, Gursoy UK, Marakoglu K, Cakmak H, Ataoglu T. Periodontitis as a risk factor for preterm low birth weight. Yonsei Med J Apr 30;49(2):200-3. Boggess KA; Society for Maternal-Fetal Medicine Publications Committee. Maternal oral health in pregnancy. Obstet Gynecol Apr;111(4): Review. Pitiphat W, Joshipura KJ, Gillman MW, Williams PL, Douglass CW, Rich-Edwards JW. Maternal periodontitis and adverse pregnancy outcomes. Community Dent Oral Epidemiol Feb;36(1):3-11. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet Jan 5;371(9606): Review. Dasanayake AP, Gennaro S, Hendricks-Muñoz KD, Chhun N. Maternal periodontal disease, pregnancy, and neonatal outcomes. MCN Am J Matern Child Nurs Jan-Feb;33(1):45-9. Review. Vettore MV, Leal M, Leão AT, da Silva AM, Lamarca GA, Sheiham A. The relationship between periodontitis and preterm low birthweight. J Dent Res Jan;87(1):73-8. Riferimenti bibliografici Revisioni sistematiche Xiong X, Buekens P, Fraser WD, Beck J, Offenbacher S. Periodontal disease and adverse pregnancy outcomes: a systematic review. BJOG Feb;113(2): Review. Three clinical trial (2 non randomizzati !!!) studies suggest that oral prophylaxis and periodontal treatment can lead to a 57% reduction in preterm low birthweight (pooled RR 0.43; 95% CI ) and a 50% reduction in preterm births (RR 0.5; 95% CI ). Khader YS, Ta'ani Q. Periodontal diseases and the risk of preterm birth and low birth weight: a meta-analysis. J Periodontol Feb;76(2): Review. RESULTS: Pregnant women with periodontal disease had an overall adjusted risk of preterm birth that was 4.28 (95% confidence interval [CI], 2.62 to 6.99; P <0.005) times that risk for healthy subjects. The overall adjusted odds ratio of preterm low birth weight was 5.28 (95% CI, 2.21 to 12.62; P <0.005), while the overall adjusted odds ratio of a delivery of either PTB or LBW was 2.30 (95% CI, 1.21 to 4.38; P <0.005). Scannapieco FA, Bush RB, Paju S. Periodontal disease as a risk factor for adverse pregnancy outcomes. A systematic review. Ann Periodontol Dec;8(1):70-8. Review. Studi clinici randomizzati disponibili 6 - Tarannum F, Faizuddin M. Effect of periodontal therapy on pregnancy outcome in women affected by periodontitis. J Periodontol Nov;78(11): 5 - Offenbacher S, Lin D, Strauss R, McKaig R, Irving J, Barros SP, Moss K, Barrow DA, Hefti A, Beck JD. Effects of periodontal therapy during pregnancy on periodontal status, biologic parameters, and pregnancy outcomes: a pilot study. J Periodontol Dec;77(12): 4 - Michalowicz BS, Hodges JS, DiAngelis AJ, Lupo VR, Novak MJ, Ferguson JE, Buchanan W, Bofill J, Papapanou PN, Mitchell DA, Matseoane S, Tschida PA; OPT Study. Treatment of periodontal disease and the risk of preterm birth. N Engl J Med Nov 2;355(18): 3 - Sadatmansouri S, Sedighpoor N, Aghaloo M. Effects of periodontal treatment phase I on birth term and birth weight. J Indian Soc Pedod Prev Dent Mar;24(1):23-6. 2 - López NJ, Da Silva I, Ipinza J, Gutiérrez J. Periodontal therapy reduces the rate of preterm low birth weight in women with pregnancy-associated gingivitis. J Periodontol Nov;76(11 Suppl): 1 - López NJ, Smith PC, Gutierrez J. Periodontal therapy may reduce the risk of preterm low birth weight in women with periodontal disease: a randomized controlled trial. J Periodontol Aug;73(8): Tarannum F, Faizuddin M. Effect of periodontal therapy on pregnancy outcome in women affected by periodontitis. J Periodontol Nov;78(11): Offenbacher S, Lin D, Strauss R, McKaig R, Irving J, Barros SP, Moss K, Barrow DA, Hefti A, Beck JD. Effects of periodontal therapy during pregnancy on periodontal status, biologic parameters, and pregnancy outcomes: a pilot study. J Periodontol Dec;77(12): Michalowicz BS, Hodges JS, DiAngelis AJ, Lupo VR, Novak MJ, Ferguson JE, Buchanan W, Bofill J, Papapanou PN, Mitchell DA, Matseoane S, Tschida PA; OPT Study. Treatment of periodontal disease and the risk of preterm birth. N Engl J Med Nov 2;355(18): Sadatmansouri S, Sedighpoor N, Aghaloo M. Effects of periodontal treatment phase I on birth term and birth weight. J Indian Soc Pedod Prev Dent Mar;24(1):23-6. López NJ, Da Silva I, Ipinza J, Gutiérrez J. Periodontal therapy reduces the rate of preterm low birth weight in women with pregnancy-associated gingivitis. J Periodontol Nov;76(11 Suppl): López NJ, Smith PC, Gutierrez J. Periodontal therapy may reduce the risk of preterm low birth weight in women with periodontal disease: a randomized controlled trial. J Periodontol Aug;73(8): Offenbacher S, Beck JD, Jared HL, Mauriello SM, Mendoza LC, Couper DJ, Stewart DD, Murtha AP, Cochran DL, Dudley DJ, Reddy MS, Geurs NC, Hauth JC; Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators. Effects of periodontal therapy on rate of preterm delivery: a randomized controlled trial. Obstet Gynecol Sep;114(3):551-9. OBJECTIVE: To test the effects of maternal periodontal disease treatment on the incidence of preterm birth (delivery before 37 weeks of gestation). METHODS: The Maternal Oral Therapy to Reduce Obstetric Risk Study was a randomized, treatment-masked, controlled clinical trial of pregnant women with periodontal disease who were receiving standard obstetric care. Participants were assigned to either a periodontal treatment arm, consisting of scaling and root planing early in the second trimester, or a delayed treatment arm that provided periodontal care after delivery. Pregnancy and maternal periodontal status were followed todelivery and neonatal outcomes until discharge. The primary outcome (gestational age less than 37 weeks) and the secondary outcome (gestational age less than 35 weeks) were analyzed using a chi test of equality of two proportions. RESULTS: The study randomized 1,806 patients at three performance sites and completed 1,760 evaluable patients. At baseline, there were no differences comparing the treatment and control arms for any of the periodontal or obstetric measures. The rate of preterm delivery for the treatment group was 13.1% and 11.5% for the control group (P=.316). There were no significant differences when comparing women in the treatment group with those in the control group with regard to the adverse event rate or the major obstetric and neonatal outcomes. ONCLUSION: Periodontal therapy did not reduce the incidence of preterm delivery. LEVEL OF EVIDENCE: I. Cruz SS, Costa Mda C, Gomes-Filho IS, Rezende EJ, Barreto ML, Dos Santos CA, Vianna MI, Passos JS, Cerqueira EM. Contribution of periodontal disease in pregnant women as a risk factor for low birth weight. Community Dent Oral Epidemiol Dec;37(6): Epub 2009 Aug 20. Starting in the 1990s, several authors sought to investigate the hypothesis that periodontitis during pregnancy may contribute towards the birth of low-weight children. However, this relationship is still not well established. The aim of this study was to evaluate whether this oral infection is associated with this gestational event. METHODS: This was a case-control study among 548 puerperae, of whom 164 were the mothers of low-weight live births (case group) and 384 were the mothers of live births of normal gestational weight (control group). They were selected at two public hospital units in two municipalities in the State of Bahia. From interviews and data gathered using live birth cards or birth certificates, information was obtained regarding age, height, previous diseases, marital status, socioeconomic situation, smoking and alcohol use. Mothers who presented at least four teeth on which one or more sites had a probing depth of greater than or equal to 4 mm, clinical attachment loss of greater than or equal to 3 mm and bleeding on probing, at the same site, were deemed to present periodontal disease. The data were analysed by stratification from logistic regression. RESULTS: Periodontal disease was diagnosed in 42.7% of the case group and 30% of the control group. A statistically significant association was found between periodontal disease and low birth weight (unadjusted OR = 1.74; 95% CI: ), particularly among mothers with low schooling levels (adjusted OR = 2.30; 95% CI: ). CONCLUSION: The findings suggest an association between periodontal disease and low birth weight among mothers with low education levels. International Centre on Birth Defects 15 15

16 Infezioni periodontali
Corso sul Counseling Preconcezionale Pacchetto formativo completo Raccomandazione Tutte le donne, per il loro benessere, devono essere incoraggiate a curare l’igiene orale e controllare l’esistenza di eventuali periodontiti. Perché Le periodontite possono rappresentare un fattore di rischio per la prematurità. Le prove di efficacia sulla riduzione del rischio di prematurità dopo il trattamento delle periodontiti nel 2° trimestre di gravidanza non sono (ancora ?) robuste. Pur tuttavia la diagnosi e il trattamento di una eventuale periodontite va effettuata non solo come buona norma di salute ma soprattutto in vista della gravidanza. Riferimento bibliografico Albandar JM, Brunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, J Periodontol Jan;70(1):13-29. Marakoglu I, Gursoy UK, Marakoglu K, Cakmak H, Ataoglu T. Periodontitis as a risk factor for preterm low birth weight. Yonsei Med J Apr 30;49(2):200-3. Boggess KA; Society for Maternal-Fetal Medicine Publications Committee. Maternal oral health in pregnancy. Obstet Gynecol Apr;111(4): Review. Pitiphat W, Joshipura KJ, Gillman MW, Williams PL, Douglass CW, Rich-Edwards JW. Maternal periodontitis and adverse pregnancy outcomes. Community Dent Oral Epidemiol Feb;36(1):3-11. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet Jan 5;371(9606): Review. Dasanayake AP, Gennaro S, Hendricks-Muñoz KD, Chhun N. Maternal periodontal disease, pregnancy, and neonatal outcomes. MCN Am J Matern Child Nurs Jan-Feb;33(1):45-9. Review. Vettore MV, Leal M, Leão AT, da Silva AM, Lamarca GA, Sheiham A. The relationship between periodontitis and preterm low birthweight. J Dent Res Jan;87(1):73-8. Riferimenti bibliografici Revisioni sistematiche Xiong X, Buekens P, Fraser WD, Beck J, Offenbacher S. Periodontal disease and adverse pregnancy outcomes: a systematic review. BJOG Feb;113(2): Review. Three clinical trial (2 non randomizzati !!!) studies suggest that oral prophylaxis and periodontal treatment can lead to a 57% reduction in preterm low birthweight (pooled RR 0.43; 95% CI ) and a 50% reduction in preterm births (RR 0.5; 95% CI ). Khader YS, Ta'ani Q. Periodontal diseases and the risk of preterm birth and low birth weight: a meta-analysis. J Periodontol Feb;76(2): Review. RESULTS: Pregnant women with periodontal disease had an overall adjusted risk of preterm birth that was 4.28 (95% confidence interval [CI], 2.62 to 6.99; P <0.005) times that risk for healthy subjects. The overall adjusted odds ratio of preterm low birth weight was 5.28 (95% CI, 2.21 to 12.62; P <0.005), while the overall adjusted odds ratio of a delivery of either PTB or LBW was 2.30 (95% CI, 1.21 to 4.38; P <0.005). Scannapieco FA, Bush RB, Paju S. Periodontal disease as a risk factor for adverse pregnancy outcomes. A systematic review. Ann Periodontol Dec;8(1):70-8. Review. Studi clinici randomizzati disponibili 6 - Tarannum F, Faizuddin M. Effect of periodontal therapy on pregnancy outcome in women affected by periodontitis. J Periodontol Nov;78(11): 5 - Offenbacher S, Lin D, Strauss R, McKaig R, Irving J, Barros SP, Moss K, Barrow DA, Hefti A, Beck JD. Effects of periodontal therapy during pregnancy on periodontal status, biologic parameters, and pregnancy outcomes: a pilot study. J Periodontol Dec;77(12): 4 - Michalowicz BS, Hodges JS, DiAngelis AJ, Lupo VR, Novak MJ, Ferguson JE, Buchanan W, Bofill J, Papapanou PN, Mitchell DA, Matseoane S, Tschida PA; OPT Study. Treatment of periodontal disease and the risk of preterm birth. N Engl J Med Nov 2;355(18): 3 - Sadatmansouri S, Sedighpoor N, Aghaloo M. Effects of periodontal treatment phase I on birth term and birth weight. J Indian Soc Pedod Prev Dent Mar;24(1):23-6. 2 - López NJ, Da Silva I, Ipinza J, Gutiérrez J. Periodontal therapy reduces the rate of preterm low birth weight in women with pregnancy-associated gingivitis. J Periodontol Nov;76(11 Suppl): 1 - López NJ, Smith PC, Gutierrez J. Periodontal therapy may reduce the risk of preterm low birth weight in women with periodontal disease: a randomized controlled trial. J Periodontol Aug;73(8): Tarannum F, Faizuddin M. Effect of periodontal therapy on pregnancy outcome in women affected by periodontitis. J Periodontol Nov;78(11): Offenbacher S, Lin D, Strauss R, McKaig R, Irving J, Barros SP, Moss K, Barrow DA, Hefti A, Beck JD. Effects of periodontal therapy during pregnancy on periodontal status, biologic parameters, and pregnancy outcomes: a pilot study. J Periodontol Dec;77(12): Michalowicz BS, Hodges JS, DiAngelis AJ, Lupo VR, Novak MJ, Ferguson JE, Buchanan W, Bofill J, Papapanou PN, Mitchell DA, Matseoane S, Tschida PA; OPT Study. Treatment of periodontal disease and the risk of preterm birth. N Engl J Med Nov 2;355(18): Sadatmansouri S, Sedighpoor N, Aghaloo M. Effects of periodontal treatment phase I on birth term and birth weight. J Indian Soc Pedod Prev Dent Mar;24(1):23-6. López NJ, Da Silva I, Ipinza J, Gutiérrez J. Periodontal therapy reduces the rate of preterm low birth weight in women with pregnancy-associated gingivitis. J Periodontol Nov;76(11 Suppl): López NJ, Smith PC, Gutierrez J. Periodontal therapy may reduce the risk of preterm low birth weight in women with periodontal disease: a randomized controlled trial. J Periodontol Aug;73(8): Offenbacher S, Beck JD, Jared HL, Mauriello SM, Mendoza LC, Couper DJ, Stewart DD, Murtha AP, Cochran DL, Dudley DJ, Reddy MS, Geurs NC, Hauth JC; Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators. Effects of periodontal therapy on rate of preterm delivery: a randomized controlled trial. Obstet Gynecol Sep;114(3):551-9. OBJECTIVE: To test the effects of maternal periodontal disease treatment on the incidence of preterm birth (delivery before 37 weeks of gestation). METHODS: The Maternal Oral Therapy to Reduce Obstetric Risk Study was a randomized, treatment-masked, controlled clinical trial of pregnant women with periodontal disease who were receiving standard obstetric care. Participants were assigned to either a periodontal treatment arm, consisting of scaling and root planing early in the second trimester, or a delayed treatment arm that provided periodontal care after delivery. Pregnancy and maternal periodontal status were followed todelivery and neonatal outcomes until discharge. The primary outcome (gestational age less than 37 weeks) and the secondary outcome (gestational age less than 35 weeks) were analyzed using a chi test of equality of two proportions. RESULTS: The study randomized 1,806 patients at three performance sites and completed 1,760 evaluable patients. At baseline, there were no differences comparing the treatment and control arms for any of the periodontal or obstetric measures. The rate of preterm delivery for the treatment group was 13.1% and 11.5% for the control group (P=.316). There were no significant differences when comparing women in the treatment group with those in the control group with regard to the adverse event rate or the major obstetric and neonatal outcomes. ONCLUSION: Periodontal therapy did not reduce the incidence of preterm delivery. LEVEL OF EVIDENCE: I. Cruz SS, Costa Mda C, Gomes-Filho IS, Rezende EJ, Barreto ML, Dos Santos CA, Vianna MI, Passos JS, Cerqueira EM. Contribution of periodontal disease in pregnant women as a risk factor for low birth weight. Community Dent Oral Epidemiol Dec;37(6): Epub 2009 Aug 20. Starting in the 1990s, several authors sought to investigate the hypothesis that periodontitis during pregnancy may contribute towards the birth of low-weight children. However, this relationship is still not well established. The aim of this study was to evaluate whether this oral infection is associated with this gestational event. METHODS: This was a case-control study among 548 puerperae, of whom 164 were the mothers of low-weight live births (case group) and 384 were the mothers of live births of normal gestational weight (control group). They were selected at two public hospital units in two municipalities in the State of Bahia. From interviews and data gathered using live birth cards or birth certificates, information was obtained regarding age, height, previous diseases, marital status, socioeconomic situation, smoking and alcohol use. Mothers who presented at least four teeth on which one or more sites had a probing depth of greater than or equal to 4 mm, clinical attachment loss of greater than or equal to 3 mm and bleeding on probing, at the same site, were deemed to present periodontal disease. The data were analysed by stratification from logistic regression. RESULTS: Periodontal disease was diagnosed in 42.7% of the case group and 30% of the control group. A statistically significant association was found between periodontal disease and low birth weight (unadjusted OR = 1.74; 95% CI: ), particularly among mothers with low schooling levels (adjusted OR = 2.30; 95% CI: ). CONCLUSION: The findings suggest an association between periodontal disease and low birth weight among mothers with low education levels. International Centre on Birth Defects 16 16