LEITE, F. Influência da restrição de crescimento intra-uterino na idade da menarca: estudo da coorte de nascidos vivos de Ribeirão Preto de 1978/9. 2008. 85 p. Dissertação (Mestrado) apresentada à Faculdade de Medicina de Ribeirão Preto/USP. A idade da menarca é um marco da puberdade e, quando antecipada, parece estar associada a um maior risco de desenvolvimento de câncer de mama, síndrome metabólica e obesidade. É possível que alterações no ambiente intrauterino, como a restrição de crescimento do feto, levem a interferências no sistema hipotálamo-hipófise-gonadal resultando em alterações na idade da menarca. Em vista da controvérsia dos fatores que influenciam na idade da menarca, este estudo testou a hipótese da associação entre restrição de crescimento intra-uterino (baixo peso ao nascer, pequeno para idade gestacional, restrição intra-uterina de Kramer) e antecipação da idade da menarca. Em uma sub-amostra foi testada a possível interação entre a restrição de crescimento intra-uterino e o índice de massa corpórea. Para esse estudo foram utilizadas informações coletadas nos seguimentos de 1987/9 e 2004/5 de 1056 meninas nascidas em Ribeirão Preto, provenientes do estudo de coorte dos nascidos vivos em Ribeirão Preto de 1978/9. Menarca antecipada foi definida como primeiro sangramento vaginal ocorrido antes dos 12 anos de idade. Análise univariada foi seguida de análise bivariada e multivariada por meio de modelo generalizado empregando distribuição de Poisson para estimativa de riscos relativos e erro padrão por meio de método robusto. Os fatores de confusão controlados foram idade, escolaridade e situação conjugal da mãe, número de irmãos, comprimento ao nascer, prematuridade e índice de massa corpórea (apenas para a subamostra). Em média, a menarca ocorreu aos 12,3 anos (DP=1,5). A ocorrência de menarca antecipada foi de 27,7% (n= 293) para a coorte inteira e de 29,1% (n= 172) na sub-amostra. Foi encontrada associação negativa entre restrição de crescimento intra-uterino, seja representado por baixo peso ao nascer (Risco Relativo, RR= 0,47; Intervalo de Confiança de 95%, IC95%: 0,26-0,84), pequeno para idade gestacional (RR = 0,57;IC95%:0,37-0,89) ou restrição de Kramer (RR= 0,65; IC95%:0,47-0,92), com a antecipação da idade da menarca. Os resultados foram semelhantes na análise da sub-amostra, porém sem significância estatística. Quando o índice de massa corpórea foi considerado na análise da sub-amostra, não houve modificação dos resultados. Desta forma, este estudo demonstrou associação negativa entre restrição de crescimento intra-uterino e antecipação da idade da menarca, ou seja, a restrição de crescimento foi fator de proteção da menarca antecipada. / LEITE, F. Influence of intrauterine growth restriction on the age of menarche: the cohort study of live births of Ribeirao Preto in 1978/9. 2008. 85 p. Dissertation (Master) submitted to the Faculty of Medicine of Ribeirao Preto/USP. This study tested the hypothesis of association between intrauterine growth restriction and early age of menarche. For this study, follow-up data (n = 1056) from the population based livebirth cohort study of Ribeirao Preto of 19789 were analyzed. Early menarche was defined as having the first menstrual event before 12 years-old and intrauterine growth restriction was defined by three measurements: low birthweight (< 2500grs), small for gestational age (< 10% Williams growth curve) and fetal growth ratio (< 0.85 mean weight for gestational age). Relative risks were estimated by generalized estimation equations (Poisson distribution) with robust method for estimation of standard errors. Analyzes were adjusted for maternal age, education and marital status, number of siblings, birth length and preterm. Body mass index was tested as intervenient or interaction factor in a subsample of the cohort examined at 9 yrs-old. The mean age of menarche was 12.3 years (Standard Deviation = 1.5). Early menarche was observed for 27.7% for the entire cohort and 29.1% for the sub-sample. Negative association was observed between intrauterine growth restriction and early menarche. The adjusted relative risks and respective confidence intervals (95% CI) for low birth weight, small for gestational age and fetal growth ratio were respectively: 0.47 (95% CI: 0.26-0.84), 0.57 (95% CI: 0,37-0,89), and 0.65 (95%CI: 0,47-0, 92). No evidence that body mass index was an intermediate or interaction factor was observed. Thus, this study showed a negative association between intrauterine growth restriction and anticipation of age of menarche.

OBJETIVO: O objetivo deste estudo foi investigar o uso de progesterona natural vaginal para a prevenção de parto prematuro em gestações gemelares. Delineamento do estudo: foi realizado um estudo prospectivo, randomizado, duplo-cego, placebo controlado, que avaliou 390 gestações gemelares concebidas naturalmente entre mães sem história de prematuridade que estavam recebendo cuidados pré-natais em centro único. Mulheres com gestações entre 18 e 21 semanas e 6 dias foram aleatoriamente randomizadas para o grupo progesterona vaginal diária (200 mg) ou placebo até 34 semanas e 6 dias de gestação. O desfecho primário foi a diferença de idade gestacional média no parto; os resultados secundários foram a taxa de parto espontâneo < 34 semanas de gestação e a taxa de mortalidade e morbidade neonatal composta entre os grupos. RESULTADOS: As características gerais dos grupos foram semelhantes. A análise final incluiu 189 mulheres no grupo progesterona e 191 no grupo placebo. Nenhuma diferença (p=0,095) na idade gestacional média foi observada entre o grupo progesterona (35,08 ± 3,19 [DP]) e placebo (35,55 ± 2,85). A incidência de parto espontâneo com < 34 semanas de gestação foi de 18,5% no grupo de progesterona e 14,6% no grupo placebo (OR = 1,32; 95% intervalo de confiança, 0,24 - 2,37). Nenhuma diferença no resultado neonatal composto e mortalidade foi observada entre a progesterona (15,5%) e o grupo placebo (15,9%) (odds ratio, 1,01; 95% intervalo de confiança, 0,58 - 1,75). CONCLUSÃO: Em gestação gemelar, população não selecionada, o uso de progesterona natural micronizada 200mg/dia não reduz a incidência de parto prematuro espontâneo / OBJECTIVE: The purpose of this study was to investigate the use of vaginal progesterone for the prevention of preterm delivery in twin pregnancies. STUDY DESIGN: We conducted a prospective, randomized, double-blind, placebo-controlled trial that involved 390 naturally conceived twin pregnancies among mothers with no history of preterm delivery who were receiving antenatal care at a single center. Women with twin pregnancies between 18 and 21 weeks and 6 days\' gestation were assigned randomly to daily vaginal progesterone (200 mg) or placebo ovules until 34 weeks and 6 days\' gestation. The primary outcome was the difference in mean gestational age at delivery; the secondary outcomes were the rate of spontaneous delivery at < 34 weeks\' gestation and the rate of neonatal composite morbidity and mortality in the treatment and no treatment groups. RESULTS: The baseline characteristics were similar in both groups. The final analysis included 189 women in the progesterone group and 191 in the placebo group. No difference (P .095) in the mean gestational age at delivery was observed between progesterone (35.08 ± 3.19 [SD]) and placebo groups (35.55 ± 2.85). The incidence of spontaneous delivery at < 34 weeks\' gestation was 18.5% in the progesterone group and 14.6% in the placebo group (odds ratio, 1.32; 95% confidence interval, 0.24 - 2.37). No difference in the composite neonatal morbidity and mortality was observed between the progesterone (15.5%) and placebo (15.9%) groups (odds ratio, 1.01; 95% confidence interval, 0.58 -1.75). CONCLUSION: In non-selected twin pregnancies, vaginal progesterone administration does not prevent preterm delivery

The birth of low weight babies in the United States has not had a meaningful decline for the last 10 years.It continues to be a major predictor of fetal-infant mortality. In addition, the rate of low birth weight infants among African American women continues to be twice that of European American women. Low birth weight babies may experience breathing problems, vision problems, diabetes, hypertension, and cerebral palsy. The purpose of this study was to examine why the high infant mortality rate persist among the African American communities of Southeast Queens, New York City as compared to European American communities in the Borough of Queens, New York City.This was a quantitative retrospective study with a correlational design that utilized secondary data derived from vital records maintained by the New York City Department of Health and Mental Hygiene. The investigation was guided by the ecological model as the theoretical framework to collect, assess, and analyze the data. Logistic regression was used to predict the association of risk factors to infant mortality. Low birth weight, preterm birth, late or no prenatal care, and smoking during pregnancy were risk factors associated with a high mortality rate among African American women. Positive social change implications for this study include the development of a social intervention that will be culturally based for the diverse communities of Southeast Queens, New York City. There will be a collaborative effort in implementing the evidence-based interventions involving interested stakeholders.

<p>The studies were undertaken to evaluate risk factors and outcomes in small-for-gestational-age (SGA) births, in cohort studies using the population-based Swedish Birth, Twin and Education Registers. A cohort study of pregnant women from Uppsala County evaluated the effect on birthweight by caffeine.</p><p> Maternal anthropometrics influence risks of SGA at all gestational ages. Smoking increases risks of moderately preterm and term SGA, while hypertensive disorders foremost increase the risk of preterm SGA. Monozygotic twin mothers have higher concordance rates in offspring birthweight-for-gestational length than dizygotic twin mothers, indicating genetic effects on fetal growth. Caffeine is not associated with a reduction in birthweight or birthweight-for-gestational age.</p><p> The increased risk of stillbirth in postterm pregnancies is explained by increased rates of SGA in postterm pregnancies. Births with malformations account for a large part of the SGA-related increased risk of infant death. SGA, as defined by an individualised birth-weight standard, is a better predictor of adverse pregnancy outcomes than the commonly used population-based birthweight standard. </p><p> Risk factors for SGA, as well as the prognosis for the SGA infant, vary with gestational age. However, the commonly used definition of SGA is probably a poor predictor of intrauterine growth retardation.</p>

The studies were undertaken to evaluate risk factors and outcomes in small-for-gestational-age (SGA) births, in cohort studies using the population-based Swedish Birth, Twin and Education Registers. A cohort study of pregnant women from Uppsala County evaluated the effect on birthweight by caffeine. Maternal anthropometrics influence risks of SGA at all gestational ages. Smoking increases risks of moderately preterm and term SGA, while hypertensive disorders foremost increase the risk of preterm SGA. Monozygotic twin mothers have higher concordance rates in offspring birthweight-for-gestational length than dizygotic twin mothers, indicating genetic effects on fetal growth. Caffeine is not associated with a reduction in birthweight or birthweight-for-gestational age. The increased risk of stillbirth in postterm pregnancies is explained by increased rates of SGA in postterm pregnancies. Births with malformations account for a large part of the SGA-related increased risk of infant death. SGA, as defined by an individualised birth-weight standard, is a better predictor of adverse pregnancy outcomes than the commonly used population-based birthweight standard. Risk factors for SGA, as well as the prognosis for the SGA infant, vary with gestational age. However, the commonly used definition of SGA is probably a poor predictor of intrauterine growth retardation.

The objectives of the thesis was to explore partner violence during pregnancy in Nicaragua – its prevalence and characteristics, how women perceive, understand and cope with it, its association with specific child outcomes such as low birth weight (LBW), small for gestational age (SGA) and preterm birth, and possible pathways. A cross-sectional community-based study was conducted with 478 pregnant women and for a sub-sample of 147 salivary cortisol was measured. A case-referent hospital-based study was organized including 303 mothers immediately after delivery. In-depth interviews were conducted with women survivors to increase understanding of partner violence during pregnancy. The prevalence of emotional, physical and sexual partner abuse during pregnancy was 32.4%, 13.4% and 6.7% respectively. Seventeen percent of the victims suffered all three types of violence and in two thirds the abuse was severe and repeated. Half of the abused women had experienced punches and kicks directed to the abdomen; however, only 14% had sought health care and very few had disclosed the abuse or contacted police or authorities. Adolescent mothers, unwanted pregnancy and late registration for antenatal care or no check-ups were more likely among victims. The access to social resources facilitated the women’s ability to cope with the abuse, but the pregnancy itself was a barrier to receiving support from family, friends or society. The ability to confront abuse was determined by a complex interplay of factors such as economic independence, severity of abuse, access to social resources, implications for important others (i.e. children), socioeconomic group and a personal ability to cope with social norms. Low social resources, high levels of emotional distress and attempted suicide were associated with violence during pregnancy. Abuse during pregnancy was also found as an independent risk factor for LBW. Sixteen percent of LBW was attributed to physical abuse by a partner during pregnancy. A significant association between abuse during the index pregnancy and SGA was found. Partner violence during the pregnancy, low social resources and emotional distress were associated with higher levels of salivary cortisol. Pregnant women with high cortisol values were significantly more likely to give birth to SGA babies. A substantial decrease of birthweight, 142 grams, was estimated to be associated with increases in cortisol due to violence exposure. Partner violence during pregnancy is a serious social problem that impacts the rights, health and wellbeing of both the woman and her unborn child. The studies call for prioritization of intervention programmes for prevention and detection of violence, treatment and rehabilitation of the victims and the perpetrators, and change of the structural causes producing violence in society.

A case-control study was performed to evaluate the Swedish population-based symphysis fundus (SF) reference curves. The study included 242 small for gestational age (SGA) neonates (169 term and 73 preterm infants) as cases and 296 non-SGA infants as controls. Two Swedish SF curves were evaluated. In term pregnancies they showed a sensitivity of 32 % and 51 % and a specificity of 90 % and 83 %, respectively, at a cut-off level of &lt; - 2 SD from the mean according to the SF reference curve. The sensitivity for SGA was higher in preterm pregnancies (49 % and 58 %, respectively) and the first alarm below – 2 SD was noted before 32 weeks in 37 % and 43 % of the preterm pregnancies, respectively. (Study I) A study of self-administered SF measurements was designed to achieve more regular and frequent SF measurements. Thirty-three women with singleton, ultrasound dated pregnancies performed SF measurements on average 14 weeks from gestational week 20 to 25 until delivery. Self-administered SF measurements were higher and had higher variance than midwives’ measurements. Four consecutive SF measurements on each occasion can compensate for higher variance. Reliable self-administered SF measurements can be obtained. (Study II) Self-administered SF measurements from 191 women were used to construct absolute and relative SF growth references. The influence of fetal sex, maternal obesity and parity was assessed in regression models. The lnSF growth was statistically influenced by maternal obesity, and a borderline significance was recorded for fetal sex and parity. Statistical analysis and graphical displays show no evidence that the relative lnSF growth should be dependent on these variables. (Study III) To improve detection of infants with intrauterine growth restriction (IUGR) rather than SGA a new statistical model (the SR method) was used. The SR method was evaluated with SF measurements from 1122 pregnant women. The sensitivity for neonatal morbidity and SGA was low, between 6 and 36 % for SGA (&lt; -2SD). Neonates classified as SGA (&lt; -2SD and &lt; 10th percentile) had increased morbidity compared with the total study group. Neonates suspected to be SGA before delivery by the population-based SF measurement method had lower morbidity than those not suspected. The SR method was found not to improve detection of fetuses with increased morbidity or SGA neonates in this study. Better screening methods to detect IUGR and SGA prior to delivery are needed. (Study IV)

Altered DNA methylation may lead to suboptimal fetal programming, increasing the risk of adverse pregnancy outcomes such as small for gestational age (SGA); however, few studies have examined the associations between DNA methylation, prenatal exposures, and fetal outcomes. Cross-sectional data from a larger, ongoing study were used to assess the impact of prenatal smoking on gene specific methylation of umbilical cord blood derived DNA and to investigate the association between gene-specific methylation and risk of SGA. The association between gene-specific DNA methylation and birthweight was also assessed. Maternal and infant covariates were abstracted from medical records, cigarette smoke exposure was determined by measuring cotinine in umbilical cord blood plasma, and the Illumina Infinium Methylation27 assay was used to assess CpG site specific methylation. Methylation was represented by a beta value ranging from 0 to 1. Gene-level methylation was calculated by averaging the methylation levels over the CpG sites interrogated in that gene. Logistic regression was used to generate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between SGA and methylation of CYP1A1, HIF1A, GSTT1, and GSTM1 and the association between cotinine level and hypermethylation of CYP1A1, HIF1A, GSTT1, and GSTM1. DNA was considered hypermethylated if the beta value was greater than or equal to the 75th percentile. Univariate and multivariable linear regression were used to examine the association between birthweight and methylation of the IGF1 and IGF2 gene. The analyses included 90 singleton births. A 0.10 unit increase in methylation of GSTT1 increased the risk of SGA almost 3-fold (OR=2.69, 95%CI=1.34, 5.43). A 5ng/ml increase in cotinine level increased the risk of hypermethylation of GSTT1 (OR=1.18, 95%CI=1.02, 1.37). Birthweight did not appear to be impacted by methylation of IGF2 (β=0.07, 95%CI=-2.91, 3.05), but a one standard deviation increase in methylation of IGF1 was associated with a 3.63% decrease in birthweight (95%CI= -6.49, -0.78). No differences in DNA methylation by prenatal vitamin intake were detected. These findings suggest that DNA methylation plays a critical role in fetal growth and may mediate the risk of SGA and low birthweight.

In this retrospective cohort from 2002 through 2007, 104,003 singleton live births in Hillsborough County, Florida were analyzed to elucidate the relationship between feto-infant morbidity outcomes and prenatal exposure to six criteria air pollutants. This study is based on three linked databases: The Florida Hospital Discharge database; The vital statistics records of singleton live births; Air Pollution meteorological data from the Environmental Protection Agency. There are six common air pollutants, particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), ground-level ozone (O3), carbon monoxide (CO), nitrogen (NOx), and lead (Pb). These pollutants are harmful to human health and the environment. The primary outcomes of interest were low birth weight (LBW), preterm births, and small for gestational age (SGA). The intent of this project is to address these issues of air pollution effects and the methodology surrounding the study of air pollution. Using modeling, exposure values of the six criteria air pollutants were assigned to mothers over their period of pregnancy. To address these methodological concerns, this study utilizes the structural equation modeling, quartile groupings with dose response, and trimester groupings to evaluate the relationship between air pollution and birth outcomes of pregnant residents. Using structural equation modeling a significant B value of 0.35 indicated that exposure to the six criteria pollutant in pregnancy may have a significant relationship to all five birth outcomes if they are broken down into latent variables. Quartile data demonstrated that NOx seemed to have most significant associations with all outcomes with a dose response for SGA. PM10 and PM2.5 had some association to LBW and VLBW at high levels. PM10 demonstrated significance in the higher doses for SGA. However, the only dose response relationship that was demonstrated for PM10 and PM2.5 was in VLBW. PM10 also demonstrated a dose response with very preterm. If sub-divided into trimester data, PM10 demonstrated a significant relationship between exposures in all trimesters and LBW, VLBW, and SGA. PM2.5 demonstrated a significant relationship between exposures in all trimesters and VLBW. CO demonstrated a significant relationship in the 2nd trimester for LBW as well as for SGA. Mothers and their babies are a vulnerable population who are more susceptible to lower levels of pollution. These air pollutants can possibly have long-term effect on their children. Implantation of laws and regulations, warning system, or more strict EPA standards may be needed to adequately control the cost to our society.

In order to better understand the statistical relationship between measures of birthweight and gestational age and their effects on infant mortality, national vital statistics data was examined using non-parametric regression techniques (GAM) that allow for a sophisticated and detailed analysis of infant mortality models. These models allow for various non-linear effects of birthweight and gestational age on infant mortality to be quantified based upon extant methodologies (Solis, Pullum and Frisbie, 2000). Utilizing over-time, race/ethnicand sex-specific approaches, the identification of "zones" of optimal birth outcomes based upon infant mortality probabilities is successfully accomplished. This process results from the creation of a rigorous cross-classification of GAMsupplied birthweight and gestational age parameters. From these results, I find that Non-Hispanic Black infants still exhibit an infant mortality disadvantage relative to Non-Hispanic Whites and Mexican American infants. For the four birth outcome parameters and their interactions, I find evidence of infant mortality disadvantage for infants that are early or late as well as small or heavy relative to their race/ethnic-specific, birthweight-adjusted optima.