Ira M. Bernstein

Maternal Smoking and Its Association With Birth Weight

OBJECTIVE: Maternal smoking has been associated with a reduction in newborn birth weight. We sought to estimate how the pattern of maternal smoking throughout pregnancy influences newborn size. METHODS: One hundred sixty pregnant smoking women were enrolled in a prospective study. We collected data on maternal age, education, prepregnancy body mass index, and parity, as well as alcohol and illicit drug use. Cigarette use was defined as self-reported consumption before pregnancy, at the time of study enrollment, and in the third trimester. Statistical analyses were performed based on bivariate correlations and multiple linear regression. RESULTS: Of the smoking parameters examined, maternal third-trimester cigarette consumption was the strongest predictor of birth weight percentile (partial r = –0.23, P < .001). For each additional cigarette per day that a participant smoked in the third trimester, there was an estimated 27 g reduction in birth weight. Prepregnancy smoking volume was not significantly associated with birth weight percentile in bivariate (r = –0.06, P = .47) or multivariable analyses. Additional factors contributing to birth weight include gestational age (partial r = 0.69, P < .001), maternal body mass index (partial r = 0.23, P < .001), and parity (partial r = 0.16, P < .004). In total, these 4 variables explain 61% of the variance in newborn birth weight. CONCLUSION: Maternal third-trimester cigarette consumption is a strong and independent predictor of birth weight percentile. This supports the hypothesis that reductions in maternal cigarette consumption during pregnancy will result in improved birth weight, regardless of the prepregnancy consumption levels. LEVEL OF EVIDENCE: III

Effects of voucher-based incentives on abstinence from cigarette smoking and fetal growth among pregnant women.

AIMS This study examined whether voucher-based reinforcement therapy (VBRT) contingent upon smoking abstinence during pregnancy is an effective method for decreasing maternal smoking during pregnancy and improving fetal growth. DESIGN, SETTING AND PARTICIPANTS A two-condition, parallel-groups, randomized controlled trial was conducted in a university-based research clinic. A total of 82 smokers entering prenatal care participated in the trial. INTERVENTION Participants were assigned randomly to either contingent or non-contingent voucher conditions. Vouchers exchangeable for retail items were available during pregnancy and for 12 weeks postpartum. In the contingent condition, vouchers were earned for biochemically verified smoking abstinence; in the non-contingent condition, vouchers were earned independent of smoking status. MEASUREMENTS Smoking outcomes were evaluated using urine-toxicology testing and self-report. Fetal growth outcomes were evaluated using serial ultrasound examinations performed during the third trimester. FINDINGS Contingent vouchers significantly increased point-prevalence abstinence at the end-of-pregnancy (41% versus 10%) and at the 12-week postpartum assessment (24% versus 3%). Serial ultrasound examinations indicated significantly greater growth in terms of estimated fetal weight, femur length and abdominal circumference in the contingent compared to the non-contingent conditions. CONCLUSIONS These results provide further evidence that VBRT has a substantive contribution to make to efforts to decrease maternal smoking during pregnancy and provide new evidence of positive effects on fetal health.

A pilot study on voucher-based incentives to promote abstinence from cigarette smoking during pregnancy and postpartum

We report results from a pilot study examining the use of vouchers redeemable for retail items as incentives for smoking cessation during pregnancy and postpartum. Of 100 study-eligible women who were still smoking upon entering prenatal care, 58 were recruited from university-based and community obstetric practices to participate in a smoking cessation study. Participants were assigned to either contingent or noncontingent voucher conditions. Vouchers were available during pregnancy and for 12 weeks postpartum. In the contingent condition, vouchers were earned for biochemically verified smoking abstinence. In the noncontingent condition, vouchers were earned independent of smoking status. Abstinence monitoring and associated voucher delivery was conducted daily during the initial 5 days of the cessation effort, gradually decreased to every other week antepartum, increased to once weekly during the initial 4 weeks postpartum, and then decreased again to every other week for the remaining 8 weeks of the postpartum intervention period. Contingent vouchers increased 7-day point-prevalence abstinence at the end-of-pregnancy (37% vs. 9%) and 12-week postpartum (33% vs. 0%) assessments. That effect was sustained through the 24-week postpartum assessment (27% vs. 0%), which was 12 weeks after discontinuation of the voucher program. Total mean voucher earnings across antepartum and postpartum were 397 US dollars (SD=414 US dollars) and 313 US dollars (SD=142 dollars) in the contingent and noncontingent conditions, respectively. The magnitude of these treatment effects exceed levels typically observed with pregnant and recently postpartum smokers, and the maintenance of effects through 24 weeks postpartum extends the duration beyond those reported previously.

Incidence and risk factors associated with abnormal postpartum glucose tolerance in women with gestational diabetes

To determine the incidence and risk factors associated with an abnormal postpartum glucose tolerance in women with gestational diabetes, 103 patients with gestational diabetes had a 2-hour, 75 gm oral glucose tolerance test 6 +/- 2 weeks (mean +/- SD) after delivery. Twenty-two percent (23/103) of results were abnormal: Three showed frank diabetes, four showed impaired glucose tolerance, and 16 were, nondiagnostic. There was a significant difference in gravidity, pregravid weight and body mass index, delivery weight, gestational age at diagnosis, fasting and 2- and 3-hour glucose level at the time of the oral glucose tolerance test during pregnancy, need for insulin therapy during gestation, and neonatal weight greater than 4000 gm in the abnormal group as compared with the normal group. Elevated fasting glucose level (p = 0.0001) and earlier gestational age at time of diagnosis of gestational diabetes (p = 0.013) were found to be most predictive of an abnormal postpartum glucose tolerance test result. These results support the importance of postpartum oral glucose tolerance testing in women with gestational diabetes.

The Relationship Between Menstrual Cycle Phase and Anterior Cruciate Ligament Injury A Case-Control Study of Recreational Alpine Skiers

Background Female athletes suffer a greater incidence of anterior cruciate ligament tears compared with male athletes when participating in common sports; however, very little is known about the factors that explain this disparity. Study Design Case-control study; Level of evidence, 3. Methods Female recreational alpine skiers with an anterior cruciate ligament rupture and age-matched control skiers provided a serum sample and self-reported menstrual history data immediately after injury. Both serum concentrations of progesterone and menstrual history were then used to group subjects into either preovulatory or postovulatory phases of the menstrual cycle. Results Analysis of serum concentrations of progesterone revealed that alpine skiers in the preovulatory phase of the menstrual cycle were significantly more likely to tear their anterior cruciate ligaments than were skiers in the postovulatory phase (odds ratio, 3.22; 95% confidence interval, 1.09-9.52; P = .027). Analysis of menstrual history data found similar results, but the difference was not statistically significant (odds ratio, 2.38; 95% confidence interval, 0.86-6.54; P = .086). Conclusion The likelihood of sustaining an anterior cruciate ligament injury does not remain constant during the menstrual cycle; instead, the risk of suffering an anterior cruciate ligament disruption is significantly greater during the preovulatory phase of the menstrual cycle compared with the postovulatory phase. Clinical Relevance Phase of menstrual cycle may be one of the risk factors that influence knee ligament injury among female alpine skiers. The findings from this study should be considered in subsequent studies designed to identify persons at risk for anterior cruciate ligament injury and to develop intervention strategies.

Plasma volume expansion in early pregnancy

Objective To determine the time course of plasma volume expansion in early pregnancy. Methods We prospectively measured plasma volume by Evans blue dye dilution during the menstrual (cycle day 2–3), follicular (cycle day 9–10), and luteal phases (cycle day urinary leutinizing hormone [LH] surge plus 9–10) of the menstrual cycle and at three additional time points (LH surge + 16 days, LH surge + 28 days, and LH surge + 70 days) in women achieving pregnancy. Twenty-one subjects were examined during 38 menstrual cycles to establish baseline menstrual cycle data. Ten subjects conceived within 1 year of menstrual cycle studies. All ten pregnancies were viable and reached the third trimester. Analyses used repeated-measures analysis of variance with P < .05 accepted for significance. Results Mean plasma volume was found to change significantly across the period of observation (P < .008) in those who conceived. Plasma volume at LH surge + 70 days (12 menstrual weeks, 2320 ± 280 mL) was greater than either menstrual cycle estimates or early pregnancy estimates of plasma volume. There was no difference in plasma volume at LH surge + 16 days (2077 ± 288 mL) or LH surge + 28 days (2010 ± 271 mL) compared with menstrual cycle measurements during the menstrual phase (2156 ± 292 mL), follicular phase (2036 ± 280 mL), and luteal phase (2120 ± 425 mL). There was no significant difference between those who conceived and those who did not in their mean menstrual cycle plasma volume. Conclusion Plasma volume expansion in early human pregnancy cannot be identified until after the sixth menstrual week. By 12 menstrual weeks, plasma volume has expanded by approximately 14% ± 12% (mean ± SD) over follicular phase measurements.

The Effect of Estradiol and Progesterone on Knee and Ankle Joint Laxity

Background Female athletes suffer a higher incidence of anterior cruciate ligament injuries compared to their male counterparts, and they appear to be at increased risk for these injuries when they have increased anterior-posterior knee laxity and at specific phases of the menstrual cycle. Although the mechanism by which these factors combine to increase injury risk is unclear, studies suggest that cyclic variations in joint laxity produced by hormone fluctuation during the menstrual cycle pre-dispose an athlete to increased risk of ligamentous injury. Little is known about whether joint laxity varies cyclically during the menstrual cycle and if so, whether it is modulated by cyclic variations of estradiol (E2) and progesterone (P4). Hypothesis Increased serum estradiol (E2) and progesterone (P4) levels are associated with increased ankle and knee joint laxity. Study Design Cohort study. Level of evidence, 2. Methods Ankle laxity, anterior-posterior knee laxity, and serum concentrations of estradiol (E2) and progesterone (P4) were measured during the menstrual cycle in women and at corresponding time intervals in men (controls). Ankle laxity was measured from stress radiographs and included anterior talar translation relative to the tibia and talar tilt relative to the tibia; anterior-posterior knee laxity was measured with the KT-1000 arthrometer. Results Women had greater knee and ankle laxity values compared to men. There was, however, no change in knee and ankle laxity over the normal menstrual cycle in women and no change over time in men. There was no relationship between estradiol and progesterone fluctuation and ankle and knee joint laxity. Conclusions Knee and ankle joint laxities are greater for women compared to men; however, the cyclic estradiol and progesterone fluctuations that occur during the menstrual cycle do not produce cyclic fluctuations of joint laxity. Studies using joint laxity to identify a subject at risk for ligamentous injury need only consider making measurements at a specific point in time, such as during a preseason screening evaluation.

Financial Incentives for Smoking Cessation Among Pregnant and Newly Postpartum Women

OBJECTIVE Smoking during pregnancy is the leading preventable cause of poor pregnancy outcomes in the U.S., causing serious immediate and longer-term adverse effects for mothers and offspring. In this report we provide a narrative review of research on the use of financial incentives to promote abstinence from cigarette smoking during pregnancy, an intervention wherein women earn vouchers exchangeable for retail items contingent on biochemically-verified abstinence from recent smoking. METHODS Published reports based on controlled trials are reviewed. All of the reviewed research was conducted by one of two research groups who have investigated this treatment approach. RESULTS Results from six controlled trials with economically disadvantaged pregnant smokers support the efficacy of financial incentives for increasing smoking abstinence rates antepartum and early postpartum. Results from three trials provide evidence that the intervention improves sonographically estimated fetal growth, mean birth weight, percent of low-birth-weight deliveries, and breastfeeding duration. CONCLUSIONS The systematic use of financial incentives has promise as an efficacious intervention for promoting smoking cessation among economically disadvantaged pregnant and recently postpartum women and improving birth outcomes. Additional trials in larger and more diverse samples are warranted to further evaluate the merits of this treatment approach.

Proteomic profiling of urine identifies specific fragments of SERPINA1 and albumin as biomarkers of preeclampsia

OBJECTIVE The cause of preeclampsia remains unknown and the diagnosis can be uncertain. We used proteomic-based analysis of urine to improve disease classification and extend the pathophysiologic understanding of preeclampsia. STUDY DESIGN Urine samples from 284 women were analyzed by surface-enhanced laser desorption/ionization. In the exploratory phase, 59 samples were used to extract the proteomic fingerprint characteristic of severe preeclampsia requiring mandated delivery and to develop a diagnostic algorithm. In the challenge phase, we sought to prospectively validate the algorithm in 225 women screened for a variety of high- and low-risk conditions, including preeclampsia. Of these, 19 women were followed longitudinally throughout pregnancy. The presence of biomarkers was interpreted relative to clinical classification, need for delivery, and other urine laboratory measures (ratios of protein to creatinine and soluble fms-like tyrosine kinase-1 to placental growth factor). In the translational phase, biomarker identification by tandem mass spectrometry and validation experiments in urine, serum, and placenta were used to identify, quantify, and localize the biomarkers or related proteins. RESULTS We report that women with preeclampsia appear to present a unique urine proteomic fingerprint that predicts preeclampsia in need of mandated delivery with highest accuracy. This characteristic proteomic profile also has the ability to distinguish preeclampsia from other hypertensive or proteinuric disorders in pregnancy. Pregnant women followed longitudinally who developed preeclampsia displayed abnormal urinary profiles more than 10 weeks before clinical manifestation. Tandem mass spectrometry and de novo sequencing identified the biomarkers as nonrandom cleavage products of SERPINA1 and albumin. Of these, the 21 amino acid C-terminus fragment of SERPINA1 was highly associated with severe forms of preeclampsia requiring early delivery. In preeclampsia, increased and aberrant SERPINA1 immunoreactivity was found in urine, serum, and placenta, in which it localized predominantly to placental villi and placental vascular spaces adherent to the endothelium. In addition, significant perivascular deposits of misfolded SERPINA1 aggregates were exclusively identified in preeclamptic placentae. CONCLUSION Proteomics-based characterization of urine in preeclampsia identified a proteomic fingerprint composed of SERPINA1 and albumin fragments, which can accurately diagnose preeclampsia and shows promise to discriminate it from other hypertensive proteinuric diseases. These findings provide insight into a novel pathophysiological mechanism of preeclampsia related to SERPINA1 misfolding, which may offer new therapeutic opportunities in the future.

Subclinical abnormalities of glucose metabolism in subjects with previous gestational diabetes

To investigate whether there are subclinical abnormalities of glucose metabolism in women with previous gestational diabetes that are consistent with a high incidence of diabetes mellitus in later life, eight patients with previous gestational diabetes and normal oral glucose tolerance were evaluated by means of body composition studies, intravenous glucose tolerance tests, and the hyperinsulinemic-euglycemic clamp coupled with 6-6 dideuterated glucose infusion, indirect calorimetry, and measurement of islet cell antibodies. Eight control subjects were matched for percent body fat and diet and studied in a similar fashion. Abnormalities of insulin response and insulin resistance were present in four (50%) of patients with previous gestational diabetes. Insulin resistance was significantly greater in the patients than in the control subjects. When compared with lean patients, obese patients with previous gestational diabetes had significantly greater insulin response to the intravenous glucose tolerance test and insulin resistance. These changes are consistent with reported findings of an early and progressive development of overt diabetes in patients who had gestational diabetes.