In the past decades there has been an improvement in the medical treatment of children born preterm or with reduced foetal growth. This has resulted in a much higher survival rate of these children, but also in a higher number of surviving children with chronic conditions. These changes have, in turn, increased interest in investigating the connection between birth-characteristics and outcomes in later life. The overall aim of the present thesis was to study the relations between birth-characteristics, subsequent hospitalisations, and childbearing by means of data available in Swedish population-based registries. The study population in this thesis consisted of women (and men in Paper III) born in 1973-75 according to the Medical Birth Register and the Total Population Register. Information available in other registries, such as the Hospital Discharge Register, was obtained by individual record linkage. In Paper I, 148,281 women, alive and living in Sweden at 13 years of age, were included. Of the women, 4.1% were born preterm and 5.4% were born small for gestational age, and approximately 30% of all women had given birth between 13 and 27 years of age. We found that reduced foetal growth and possibly preterm birth were related to the likelihood of giving birth during the study period. The intergenerational effects of preterm birth and reduced foetal growth were investigated in Paper II and the study population consisted of 38,720 mother-offspring pairs. An intergenerational effect of reduced foetal growth was found, and reduced foetal growth in the mother also increased the risk for preterm birth in the child. Paper III was concerned with 304,275 men and women living in Sweden at 13 years of age. Of these men and women, 30% were hospitalised during adolescence and early adulthood (i.e. between 12 and 23 years of age). We found that men and women born small for gestational age or preterm were more likely to be hospitalised, and that those born small for gestational age seemed to be more at risk compared to those born preterm. Finally, in Paper IV, the relation between hospitalisations during adolescence and the likelihood of giving birth was studied in 142,998 women living in Sweden at 20 years of age. We found that a majority of the causes of hospitalisation during adolescence were positively connected to the likelihood of giving birth between 20 and 27 years of age. The relations presented in Papers I-IV were evident although socio-economic characteristics were adjusted for.

A gemelaridade apresenta algumas intercorrências específicas, como a discordância de peso entre fetos e recém-nascidos (RNs). O objetivo do presente estudo foi predizer a discordância de peso do exame ultra-sonográfico comparada à do parto e avaliar a morbidade e a mortalidade neonatais nas gestações gemelares discordantes quanto ao peso. Este foi um estudo retrospectivo, com levantamento dos casos do período de 1998 a 2004, no Setor de Gestações Múltiplas da Clínica Obstétrica do HCFMUSP. Na avaliação da predição ultra-sonográfica, foram inseridas 221 gestações gemelares e, na avaliação da morbidade e da mortalidade, 151 gestações com partos nessa instituição. A discordância de peso foi definida como >= 20%, sendo excluídos os casos de malformações fetais (n=43) e da Síndrome da transfusão feto-fetal (n=24). Para análise da adequação do peso ao nascimento, utilizou-se a curva de Alexander et al., 1998, para gêmeos. No estudo da predição, foram utilizados quatro intervalos de tempo em relação ao parto (0 a 7 dias - n = 96; 8 a 14 dias - n = 66; 15 a 21 dias - n = 58; 22 a 28 dias - n = 59 gestações), somando 279 avaliações. No grupo de 0 a 7 dias, a estimativa da sensibilidade foi de 93,6%, especificidade de 79,4%, valor preditivo positivo de 89,2%, valor preditivo negativo de 87,1% e acurácia de 88,6%. Nos demais grupos, a sensibilidade e a acurácia foram de 95,8% e 84,9%, 95,6% e 84,5%, 90,9% e 84,8%, respectivamente. Em relação à morbidade, 111 gestações eram concordantes (73,5%) e 40 discordantes quanto ao peso. No grupo discordante, 75% das gestações gemelares apresentaram pelo menos um recém-nascido com Restrição de Crescimento Fetal (RCF). Nesta análise, as gestações gemelares concordantes monocoriônicas obtiveram menor média de idade gestacional no parto (34,3 versus 36,2 semanas, p=0,004), menor peso médio (2067 versus 2334 gramas, p=0,0016) e maior tempo de internação (10,6 versus 7,3 dias, p=0,0023) que as gestações concordantes dicoriônicas. Nas gestações discordantes, não houve diferença significativa em relação à corionicidade. As gestações discordantes, com pelo menos um RN abaixo do percentil 10, apresentaram menor média de idade gestacional (35,2 versus 36,8 semanas, p=0,009) e maior tempo de internação (17,5 versus 8,2 dias, p=0,026). Não foi observada diferença significativa de morbidade e mortalidade entre RNs concordantes e discordantes, com pesos entre os percentis 10 e 90. Os fetos menores das gestações discordantes demonstraram maior freqüência de índice de Apgar inferior a 7 (27,5% versus 7,5%, p=0,01). A avaliação da mortalidade não demonstrou diferença significativa em relação aos grupos concordantes (3,7%) e discordantes (4,5%; p = 1,00). No presente estudo, conclui-se que os quatro grupos apresentaram adequada correlação entre a discordância de peso à ultra-sonografia e no nascimento, porém com melhor predição até sete dias antes do parto. A morbidade neonatal esteve relacionada à RCF do menor feto. A discordância de peso e a corionicidade não interferiram na mortalidade neonatal. / The aim of this study was to evaluate the ability of prenatal ultrasound scans to predict fetal growth discordance in twin pregnancies and perinatal morbidity/mortality associated with these cases. This was a retrospective study (1998-2004) involving twin pregnancies that were scanned and had their delivery at our Institution (HCFMUSP). Cases with fetal malformations (n=43) or twin to twin transfusion syndrome (n=24) were excluded. The study of ultrasound scans consisted of 221 twin pregnancies. The final morbidity/mortality study group consisted of 151 twin pregnancies. Birth weight was evaluated based on twin growth charts published by Alexander et al (1998) and weight discordance as a difference >= 20%. Small for gestacional age (SGA) was defined as birth weight below the 10th centile. The study of ultrasonographic prediction of interwin discordance was made using four different intervals between ultrasound examination and delivery (0 to 7 days, n = 96; 8 to 14 days, n = 66; 15 to 21 days, n = 58; 22 to 28 days, n = 59 pregnancies), with a total of 279 ultrasound examinations. In group 0 to 7 days, the sensitivity was 93,6%, specificity was 79,4%, positive predicted values was 89,2%, negative predicted values was 87,1% and accuracy was 88,6%. In the groups 8 to 14 days, 15 to 21 days and 22 to 28 days the sensitivity and accuracy were 95,8% and 84,9%, 95,6% and 84,5%, 90,9% and 84,8%, respectively. Birthweight discordance was observed in 40 sets of twins (26.5%) and 12 cases were monochorionic MC (30%). Twenty five cases (22.5%) in the non discordant group were MC. In the non discordant group, monochorionic pregnancies showed lower gestational age at delivery (34.3 versus 36.2 wks, p=0.004), lower mean birth weight (2067g versus 2334g, p=0.0016) and longer length of stay in hospital (10.6 versus 7.3 days, p=0.0023) compared to dichorionic twins. In the group with twin birthweight discordance, there were no significant differences between MC and DC pregnancies and 75% of the cases had at least one newborn with SGA. These cases were showed lower gestational age at delivery (35.2 versus 36.8wks, p=0.009) and longer length of stay in hospital (17.5 versus 8.2 days, p=0.026). In the discordant group, the smaller twin had a higher frequency of first minute Apgar score < 7 (27.5% versus 7.5%, p=0.01). Perinatal mortality rate was similar in both groups (discordant 4.5% and concordant 3.7%, p=1.0). There were no significant differences in morbidity and mortality between concordant and discordant twins when birth weight was between the 10 th and 90 th centile. In conclusion, there was a good correlation between fetal growth discordance predicted by prenatal scan and actual birth weight discordance. Neonatal morbidity was related to SGA. Excluding fetal malformation and TTTS cases, birth weight discordance in twin pregnancies is not a significantly associated with neonatal mortality.

A gemelaridade apresenta algumas intercorrências específicas, como a discordância de peso entre fetos e recém-nascidos (RNs). O objetivo do presente estudo foi predizer a discordância de peso do exame ultra-sonográfico comparada à do parto e avaliar a morbidade e a mortalidade neonatais nas gestações gemelares discordantes quanto ao peso. Este foi um estudo retrospectivo, com levantamento dos casos do período de 1998 a 2004, no Setor de Gestações Múltiplas da Clínica Obstétrica do HCFMUSP. Na avaliação da predição ultra-sonográfica, foram inseridas 221 gestações gemelares e, na avaliação da morbidade e da mortalidade, 151 gestações com partos nessa instituição. A discordância de peso foi definida como >= 20%, sendo excluídos os casos de malformações fetais (n=43) e da Síndrome da transfusão feto-fetal (n=24). Para análise da adequação do peso ao nascimento, utilizou-se a curva de Alexander et al., 1998, para gêmeos. No estudo da predição, foram utilizados quatro intervalos de tempo em relação ao parto (0 a 7 dias - n = 96; 8 a 14 dias - n = 66; 15 a 21 dias - n = 58; 22 a 28 dias - n = 59 gestações), somando 279 avaliações. No grupo de 0 a 7 dias, a estimativa da sensibilidade foi de 93,6%, especificidade de 79,4%, valor preditivo positivo de 89,2%, valor preditivo negativo de 87,1% e acurácia de 88,6%. Nos demais grupos, a sensibilidade e a acurácia foram de 95,8% e 84,9%, 95,6% e 84,5%, 90,9% e 84,8%, respectivamente. Em relação à morbidade, 111 gestações eram concordantes (73,5%) e 40 discordantes quanto ao peso. No grupo discordante, 75% das gestações gemelares apresentaram pelo menos um recém-nascido com Restrição de Crescimento Fetal (RCF). Nesta análise, as gestações gemelares concordantes monocoriônicas obtiveram menor média de idade gestacional no parto (34,3 versus 36,2 semanas, p=0,004), menor peso médio (2067 versus 2334 gramas, p=0,0016) e maior tempo de internação (10,6 versus 7,3 dias, p=0,0023) que as gestações concordantes dicoriônicas. Nas gestações discordantes, não houve diferença significativa em relação à corionicidade. As gestações discordantes, com pelo menos um RN abaixo do percentil 10, apresentaram menor média de idade gestacional (35,2 versus 36,8 semanas, p=0,009) e maior tempo de internação (17,5 versus 8,2 dias, p=0,026). Não foi observada diferença significativa de morbidade e mortalidade entre RNs concordantes e discordantes, com pesos entre os percentis 10 e 90. Os fetos menores das gestações discordantes demonstraram maior freqüência de índice de Apgar inferior a 7 (27,5% versus 7,5%, p=0,01). A avaliação da mortalidade não demonstrou diferença significativa em relação aos grupos concordantes (3,7%) e discordantes (4,5%; p = 1,00). No presente estudo, conclui-se que os quatro grupos apresentaram adequada correlação entre a discordância de peso à ultra-sonografia e no nascimento, porém com melhor predição até sete dias antes do parto. A morbidade neonatal esteve relacionada à RCF do menor feto. A discordância de peso e a corionicidade não interferiram na mortalidade neonatal. / The aim of this study was to evaluate the ability of prenatal ultrasound scans to predict fetal growth discordance in twin pregnancies and perinatal morbidity/mortality associated with these cases. This was a retrospective study (1998-2004) involving twin pregnancies that were scanned and had their delivery at our Institution (HCFMUSP). Cases with fetal malformations (n=43) or twin to twin transfusion syndrome (n=24) were excluded. The study of ultrasound scans consisted of 221 twin pregnancies. The final morbidity/mortality study group consisted of 151 twin pregnancies. Birth weight was evaluated based on twin growth charts published by Alexander et al (1998) and weight discordance as a difference >= 20%. Small for gestacional age (SGA) was defined as birth weight below the 10th centile. The study of ultrasonographic prediction of interwin discordance was made using four different intervals between ultrasound examination and delivery (0 to 7 days, n = 96; 8 to 14 days, n = 66; 15 to 21 days, n = 58; 22 to 28 days, n = 59 pregnancies), with a total of 279 ultrasound examinations. In group 0 to 7 days, the sensitivity was 93,6%, specificity was 79,4%, positive predicted values was 89,2%, negative predicted values was 87,1% and accuracy was 88,6%. In the groups 8 to 14 days, 15 to 21 days and 22 to 28 days the sensitivity and accuracy were 95,8% and 84,9%, 95,6% and 84,5%, 90,9% and 84,8%, respectively. Birthweight discordance was observed in 40 sets of twins (26.5%) and 12 cases were monochorionic MC (30%). Twenty five cases (22.5%) in the non discordant group were MC. In the non discordant group, monochorionic pregnancies showed lower gestational age at delivery (34.3 versus 36.2 wks, p=0.004), lower mean birth weight (2067g versus 2334g, p=0.0016) and longer length of stay in hospital (10.6 versus 7.3 days, p=0.0023) compared to dichorionic twins. In the group with twin birthweight discordance, there were no significant differences between MC and DC pregnancies and 75% of the cases had at least one newborn with SGA. These cases were showed lower gestational age at delivery (35.2 versus 36.8wks, p=0.009) and longer length of stay in hospital (17.5 versus 8.2 days, p=0.026). In the discordant group, the smaller twin had a higher frequency of first minute Apgar score < 7 (27.5% versus 7.5%, p=0.01). Perinatal mortality rate was similar in both groups (discordant 4.5% and concordant 3.7%, p=1.0). There were no significant differences in morbidity and mortality between concordant and discordant twins when birth weight was between the 10 th and 90 th centile. In conclusion, there was a good correlation between fetal growth discordance predicted by prenatal scan and actual birth weight discordance. Neonatal morbidity was related to SGA. Excluding fetal malformation and TTTS cases, birth weight discordance in twin pregnancies is not a significantly associated with neonatal mortality.