Determining glomerular filtration rate in homozygous sickle cell disease: utility of serum creatinine based estimating equations.

BACKGROUND: Various estimating equations have been developed to estimate glomerular filtration rate (GFR) for use in clinical practice. However, the unique renal physiological and pathological processes that occur in sickle cell disease (SCD) may invalidate these estimates in this patient population. This study aims to compare GFR estimated using common existing GFR predictive equations to actual measured GFR in persons with homozygous SCD. If the existing equations perform poorly, we propose to develop a new estimating equation for use in persons with SCD. METHODS: 98 patients with the homozygous SS disease (55 females: 43 males; mean age 34±2.3 years) had serum measurements of creatinine, as well as had GFR measured using (99m)Tc-DTPA nuclear renal scan. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and the serum creatinine based CKD-EPI equations. The Bland-Altman limit of agreement method was used to determine agreement between measured and estimated GFR values. A SCD-specific estimating equation for GFR (JSCCS-GFR equation) was generated by means of multiple regression via backward elimination. RESULTS: The mean measured GFR±SD was 94.9±27.4 mls/min/1.73 m(2) BSA, with a range of 6.4-159.0 mls/min/1.73 m(2). The MDRD and CG equations both overestimated GFR, with the agreement worsening with higher GFR values. The serum creatinine based CKD-EPI equation performed relatively well, but with a systematic bias of about 45 mls/min. The new equation developed resulted in a better fit to our sickle cell disease data than the MDRD equation. CONCLUSION: Current estimating equations, other than the CKD-EPI equation, do not perform very accurately in persons with homozygous SS disease. A fairly accurate estimating equation, suitable for persons with GFR >60 mls/min/1.73 m(2) has been developed from our dataset and validated within a simulated dataset.

Fetal sex and differential survival in preeclampsia and eclampsia.

PURPOSE: We investigate sex differences in the incidence of stillbirth, neonatal mortality, and perinatal mortality among singletons born to mothers with preeclampsia or eclampsia. METHODS: Retrospective cohort analysis of a population-based sample of singleton births covering the period 1989 through 2005 (n = 56,313). RESULTS: The study population comprised 26,931 female (47.8%) and 29,382 male infants (52.2%; referent group). Overall, the prevalence of stillbirth, neonatal mortality and perinatal mortality were 0.68, 0.52 and 1.2%, respectively. There was no sex difference in the incidence of stillbirth, neonatal or perinatal mortality among offspring of mothers in this study. CONCLUSION: Although there was a preponderance of male infants among mothers with preeclampsia or eclampsia, we did not observe any sex-associated differences in fetal or neonatal survival among offspring of mothers with preeclampsia or eclampsia.

Neonatal outcomes of successful VBAC among obese and super-obese mothers.

OBJECTIVE: We sought to evaluate neonatal morbidity and mortality among women who experienced successful vaginal births after previous cesarean delivery (VBAC) by obesity subtypes. METHODS: Missouri maternally linked cohort data files were utilized. Analyses were restricted to successful singleton VBACs. Main study outcomes were neonatal death and neonatal morbidity. Risk estimates were obtained using logistic and hazards regression modeling. RESULTS: A total of 30,017 singleton births met inclusion criteria. The prevalence of VBAC was 2.3%. The neonatal death rate (per 1000) by maternal obesity subtype was 4.1 for moderate, 3.2 for severe, 4.5 for extreme and 14.3 for super-obese. The overall risk for neonatal morbidity was 56% greater among obese women when compared with normal weight women, with risk estimates increased incrementally with ascending body mass index (BMI) (p for trend < 0.01). CONCLUSION: Infants of obese women undergoing successful VBAC are at elevated risk for neonatal morbidity, and the risk increases progressively with ascending BMI.

Association between tobacco use in pregnancy and placenta-associated syndromes: a population-based study.

INTRODUCTION: Cigarette smoking is an established risk factor for adverse perinatal outcomes. The purpose of this study is to examine the association between maternal smoking in pregnancy and the occurrence of placental-associated syndromes (PAS). METHODS: We analyzed data from a population-based retrospective cohort of singleton deliveries that occurred in the state of Missouri from 1989 through 2005 (N = 1,224,133). The main outcome was PAS, a composite outcome defined as the occurrence of placental abruption, placenta previa, preeclampsia, small for gestational age, preterm or stillbirth. We used logistic regression models to generate adjusted odd ratios and their 95 percent confidence intervals. Non-smoking gravidas served as the referent category. RESULTS: The overall prevalence of prenatal smoking was 19.6%. Cigarette smoking in pregnancy was associated with the composite outcome of placental syndromes (odds ratio, 95% confidence interval = 1.59, 1.57-1.60). This association showed a dose-response relationship, with the risk of PAS increasing with increased quantity of cigarettes smoked. Similar results were observed between smoking in pregnancy and independent risks for abruption, previa, SGA, stillbirth, and preterm delivery. CONCLUSION: Maternal smoking in pregnancy is a risk factor for the development of placenta-associated syndrome. Smoking cessation interventions in pregnancy should continue to be encouraged in all maternity care settings.

Impact of prenatal alcohol consumption on placenta-associated syndromes.

The biology of placental and fetal development suggests that alcohol may play a significant role in increasing the risk of feto-infant morbidity and mortality, but study results are inconsistent and the mechanism remains poorly defined. Previous studies have not examined the risk of placenta-associated syndromes (PASs: defined as the occurrence of either placental abruption, placenta previa, preeclampsia, small for gestational age, preterm, or stillbirth) as a unique entity. Therefore, we sought to examine the relationship between prenatal alcohol use and the risk of PAS among singleton births in the Missouri maternally linked data files covering the period 1989-2005. Logistic regression with adjustment for intracluster correlation was used to generate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Compared with nondrinkers, drinkers were more likely to be smokers, 35 years of age or older, black, and multiparous. Drinkers had an increased risk of PAS (OR=1.26, 95% CI=1.22,1.31) when compared with their nondrinking counterparts. The risk of PAS was progressively amplified with increasing prenatal alcohol consumption (P for trend <.01). Women who reported consuming five or more alcoholic drinks per week had more than twofold increased risk of PASs, whereas women in the lowest drinking category (one to two drinks per week) had only a slight increased risk of PAS (OR=1.09, 95% CI=1.05, 1.14). Enhanced understanding of the mechanism by which prenatal alcohol consumption leads to PAS may aid in the development of more targeted interventions designed to prevent adverse pregnancy outcomes. Screening women for alcohol use may assist providers in protecting developing fetuses from the potential dangers of prenatal alcohol use.

Alcohol consumption during pregnancy and risk of placental abruption and placenta previa.

The purpose of this study was to examine the association between prenatal alcohol consumption and the occurrence of placental abruption and placenta previa in a population-based sample. We used linked birth data files to conduct a retrospective cohort study of singleton deliveries in the state of Missouri during the period 1989 through 2005 (n = 1,221,310). The main outcomes of interest were placenta previa, placental abruption and a composite outcome defined as the occurrence of either or both lesions. Multivariate logistic regression was used to generate adjusted odd ratios, with non-drinking mothers as the referent category. Women who consumed alcohol during pregnancy had a 33% greater likelihood for placental abruption during pregnancy (adjusted odds ratio (OR), 95% confidence interval (CI) = 1.33 [1.16-1.54]). No association was observed between prenatal alcohol use and the risk of placenta previa. Alcohol consumption in pregnancy was positively related to the occurrence of either or both placental conditions (adjusted OR [95% CI] = 1.29 [1.14-1.45]). Mothers who consumed alcohol during pregnancy were at elevated risk of experiencing placental abruption, but not placenta previa. Our findings underscore the need for screening and behavioral counseling interventions to combat alcohol use by pregnant women and women of childbearing age.

Maternal alcohol use and medically indicated vs. spontaneous preterm birth outcomes: a population-based study.

BACKGROUND: The aetiology of preterm birth remains poorly understood. The purpose of this study is to investigate if an association exists between prenatal alcohol consumption and preterm birth and to determine if such an association differs by subcategories of preterm birth. METHODS: We employed vital statistics data from the state of Missouri covering the period 1989-2005 (n = 1 221 677 singleton records). The outcome of interest was preterm birth, subclassified into medically indicated and spontaneous phenotypes. Multivariate logistic regression was used to generate adjusted odds ratios, with non-drinking mothers as the referent category. RESULTS: Prenatal alcohol use was associated with elevated risk for preterm birth. The strength of association was more prominent for spontaneous preterm delivery {adjusted odds ratio (AOR) [95% confidence interval (CI)] = 1.34 (1.28-1.41)} than for medically indicated preterm birth [AOR (95% CI) = 1.16 (1.05-1.28)]. The overall risk for drinking-related spontaneous preterm birth increased with incremental rise in the number of drinks consumed per week (P for trend < 0.01). CONCLUSIONS: Prenatal alcohol use is a risk factor for preterm delivery, and especially for spontaneous preterm birth. These findings enhance our understanding of the aetiology of preterm birth and could be utilized in the development of appropriate prevention strategies that will assist in decreasing perinatal mortality and morbidity associated with preterm delivery.

The association of prepregnancy body mass index with pregnancy outcomes in triplet gestations.

The impact of obesity on triplet gestations is poorly understood. In this study, we investigate the association of obesity with birth outcomes in triplets. Triplet births in the state of Missouri from 1989 through 1997 were analyzed. Obesity was defined as maternal prepregnancy body mass index (BMI) >or=30 kg/m(2). We assessed the association between obesity and the following outcomes: stillbirth, preeclampsia, very preterm, small for gestational age (SGA), and a composite adverse birth outcome. We employed logistic regression with further correction for intracluster correlation to obtain adjusted estimates. A total of 667 triplet gestations were analyzed. As compared with normal-weight mothers, the likelihood of stillbirth and preeclampsia was higher among obese mothers (odds ratio[OR] = 3.70; 95% confidence interval [CI] = 1.37 to 9.97 and OR = 3.02; 95% CI = 1.69 to 5.40 respectively). Obese mothers were also about twice as likely to experience at least one of the adverse birth outcomes considered. Obese women with triplet gestations have about four- and threefold elevated risks for stillbirth and preeclampsia as compared with their counterparts with normal weight. This observation may be of utility in the preconceptional counseling of women considering the use of assisted reproductive technology.

Intrauterine exposure to tobacco and risk of medically indicated and spontaneous preterm birth.

We investigated the association between prenatal smoking and the occurrence of medically indicated and spontaneous preterm delivery (<37 weeks). We performed a retrospective cohort study of singleton live births in the state of Missouri (n = 1,219,159) using maternally linked cohort data files covering the period 1989 to 2005. The main outcomes of interest were spontaneous and medically indicated preterm and very preterm birth. Logistic regression models were used to generate adjusted odds ratios and their 95% confidence intervals. There were 132,246 (10.8%) infants born preterm in the study population, of which 106,410 (80.5%) were classifiable as spontaneous preterm births and 25,836 (19.5%) were medically indicated preterm deliveries. We found elevated risks for both medically indicated and spontaneous preterm birth associated with maternal cigarette smoking during pregnancy. This heightened risk was particularly evident for medically indicated preterm birth (adjusted odds ratio [95% confidence interval] = 1.48 [1.41 to 1.55]). Women who smoke during pregnancy are at increased risk for preterm birth, and especially for medically indicated preterm delivery.

Maternal prepregnancy underweight and risk of early and late stillbirth in black and white gravidas.

OBJECTIVE: The association between underweight and stillbirth remains poorly defined, especially across racial/ethnic sub-populations. We investigate the association of pre-pregnancy underweight on the risk for early and late stillbirth among black and white mothers. METHODS: We conducted analysis on the Missouri maternally linked data files covering the period 1989-1997 inclusive. Using body mass index (BMI), we categorized mothers as underweight (BMI <18.5) and normal weight (BMI = 18.5-24.9). By applying logistic regression modeling with adjustment for intracluster correlation, we estimated the risk for total, early (-28 weeks of gestation), and late stillbirth (>28 weeks of gestation) among black and white mothers. RESULTS: A total of 1808 cases of stillbirth were registered. The rate of stillbirth among white mothers was 3.7 per 1000, while the rate among blacks was 7.1 per 1000. Underweight black mothers had comparable risk for total (OR, 0.9; 95% CI, 0.7-1.2), early (OR, 1.1; 95% CI, 0.8-1.5), and late stillbirth (OR, 0.8; 95% CI, 0.5-1.2) as compared to their normal-weight counterparts. By contrast, underweight white gravidas had a 30% reduced likelihood (OR, 0.7; 95% CI, 0.6-0.9) for late stillbirth as compared to normal-weight white mothers. However, the risks for total and early stillbirth among underweight white mothers were similar to those of normal-weight white mothers. CONCLUSION: Low prepregnancy BMI has similar effects on fetal survival in both blacks and whites except for late stillbirth. The underweight white survival advantage over blacks in late pregnancy could probably be due to greater access for identified white at-risk groups to effective obstetrical interventions as previously reported.

Maternal pre-gravid body weight and risk for placental abruption among twin pregnancies.

OBJECTIVES: Placental abruption is a major cause of fetal and neonatal death and has been reported more frequently in twin pregnancies than among singleton gestations. The purpose of this article is to investigate the role of maternal pre-gravid body mass index (BMI) on the risk for placental abruption among twin pregnancies. METHODS: We used the Missouri maternally linked cohort files (years 1989-1997) consisting of twin live births (gestational age 20-44 weeks). Maternal pre-gravid weight was classified based on the following BMI-based categories: normal (18.5-24.9), underweight (<18.5), overweight (25-29.9), and obese (>30). We used logistic regression for generated adjusted odds ratios with correction for the presence of intra-cluster correlation using generalized estimating equations. RESULTS: Overall, 261 cases of placental abruption were registered over the entire study period, yielding a placental abruption rate of 14.9/1000. The frequency of placental abruption correlated negatively with maternal BMI in a dose-effect pattern: underweight (19.3/1000); normal weight (16.1/1000); overweight (13.9/1000); and obese (9.5/1000) mothers (p for trend < 0.01). After adjusting for confounders, the likelihood of placental abruption was still lower in obese women (OR = 0.58; 95% CI = 0.38-0.87). By contrast, women who were underweight had a 20-30% greater likelihood for placental abruption when compared with normal weight mothers, although these findings were statistically not significant. CONCLUSIONS: There is an inverse relationship between pre-gravid maternal BMI and placental abruption. The mechanism by which obesity impacts the likelihood of placental abruption in twin pregnancies requires further study.

Extreme maternal underweight and feto-infant morbidity outcomes: a population-based study.

OBJECTIVE: We sought to estimate the association between severity of maternal pre-pregnancy underweight and feto-infant morbidity outcomes. METHODS: Missouri maternally linked cohort records from 1989 to 1997 inclusive were analysed. Using pre-pregnancy maternal body mass index (BMI), we classified study participants into: Normal (18.5-24.9) [referent group], mild thinness (17.0-18.5), moderate thinness (16.0-16.9) and severe thinness (<16.0). We estimated the association between pre-pregnancy underweight, underweight subtypes and feto-infant morbidity outcomes using adjusted odds ratios to approximate relative risks with correction for intra-cluster correlations. RESULTS: Fetal growth curve trajectories for the two groups became divergent as from 30 gestational weeks. Underweight mothers were at increased risk for low birthweight (OR = 1.82; 95% CI = 1.77-1.88), very low birthweight (OR = 1.41; 95% CI = 1.31-1.51), small for gestational age (OR = 1.80; 95% CI = 1.76-1.84), preterm (OR = 1.37; 95% CI = 1.33-1.40) and very preterm (OR = 1.42; 95% CI = 1.34-1.50). These risk estimates increased in a dose-effect fashion with increasing severity of underweight status except for very preterm (p for trend < 0.01). CONCLUSION: Pre-pregnancy underweight is a risk factor for a spectrum of feto-infant morbidity outcomes, with risk estimates being most pronounced among extremely underweight mothers.

Obesity subtypes and risk of spontaneous versus medically indicated preterm births in singletons and twins.

Using data from the Missouri maternally linked files (1989-1997), the authors examined the association among maternal obesity, obesity subtypes, and spontaneous and medically indicated preterm (<37 weeks) and very preterm (<33 weeks) births in singletons and twins. Adjusted odds ratios were obtained with correction for intracluster correlation. The prevalence of obesity increased by 77% over the study period (p(trend) < 0.001). Obese mothers had a lower risk for spontaneous preterm birth, and this was more pronounced among twins (odds ratio = 0.68, 95% confidence interval: 0.62, 0.75) than singletons (odds ratio = 0.84, 95% confidence interval: 0.82, 0.87). However, this association was present only among obese women who gained less than 0.69 kg/week for singletons and between 0.23 and 0.69 kg/week for twins. By contrast, obese mothers with singleton gestation had about 50% greater odds of medically indicated preterm (odds ratio = 1.46, 95% confidence interval: 1.39, 1.54) and very preterm (odds ratio = 1.49, 95% confidence interval: 1.34, 1.65) births, and the risk increases with ascending severity of obesity (p(trend) < 0.01). For extreme obesity, the risk of medically indicated preterm and very preterm births was almost double that for nonobese women. Similar findings were observed in twins. These data suggest that obesity increases the risk for medically indicated but not spontaneous preterm birth in both singletons and twins.