John T. Repke

A prospective longitudinal evaluation of pregnancy in the Marfan syndrome.

OBJECTIVE We undertook a prospective evaluation of the outcomes of pregnancy, both maternal and fetal, and the long-term impact of pregnancy on Marfan syndrome in a series of consecutive, unselected patients. STUDY DESIGN Forty-five pregnancies in 21 Marfan syndrome patients were prospectively observed in one institution between 1983 and 1992. During pregnancy, patients were monitored with serial echocardiograms and close attention to symptoms. Maternal and fetal outcomes were monitored with serial echocardiographic data were analyzed by least-squares regression. Eighteen of the patients were followed up for 15 months to 13 years after the completion of their last pregnancy for investigation of the long-term impact of pregnancy on the cardiovascular manifestations of Marfan syndrome. RESULTS Aortic dissection occurred in two patients, both with increased risk for dissection established before pregnancy. The incidence of obstetric complications otherwise did not exceed that in the general population. Echocardiographic data demonstrated little to no change in aortic root diameter throughout pregnancy in most patients. Long-term follow-up showed no apparent worsening of cardiovascular status attributable to pregnancy in comparison with a group of 18 women with Marfan syndrome who were of similar age, had a similar degree of disease severity, and underwent no pregnancies. CONCLUSIONS Patients with Marfan syndrome in whom cardiovascular involvement is minor and aortic root diameter is < 40 mm usually tolerate pregnancy well, with favorable maternal and fetal outcomes, and without subsequent evidence of aggravated aortic root dilatation over time.

Midline episiotomy and anal incontinence: retrospective cohort study

Abstract Objective: To evaluate the relation between midline episiotomy and postpartum anal incontinence. Design: Retrospective cohort study with three study arms and six months of follow up. Setting: University teaching hospital. Participants: Primiparous women who vaginally delivered a live full term, singleton baby between 1 August 1996 and 8 February 1997: 209 who received an episiotomy; 206 who did not receive an episiotomy but experienced a second, third, or fourth degree spontaneous perineal laceration; and 211 who experienced either no laceration or a first degree perineal laceration. Main outcome measures: Self reported faecal and flatus incontinence at three and six months postpartum. Results: Women who had episiotomies had a higher risk of faecal incontinence at three (odds ratio 5.5, 95% confidence interval 1.8 to 16.2) and six (3.7, 0.9 to 15.6) months postpartum compared with women with an intact perineum. Compared with women with a spontaneous laceration, episiotomy tripled the risk of faecal incontinence at three months (95% confidence interval 1.3 to 7.9) and six months (0.7 to 11.2) postpartum, and doubled the risk of flatus incontinence at three months (1.3 to 3.4) and six months (1.2 to 3.7) postpartum. A non-extending episiotomy (that is, second degree surgical incision) tripled the risk of faecal incontinence (1.1 to 9.0) and nearly doubled the risk of flatus incontinence (1.0 to 3.0) at three months postpartum compared with women who had a second degree spontaneous tear. The effect of episiotomy was independent of maternal age, infant birth weight, duration of second stage of labour, use of obstetric instrumentation during delivery, and complications of labour. Conclusions: Midline episiotomy is not effective in protecting the perineum and sphincters during childbirth and may impair anal continence.

Birth weight as a predictor of brachial plexus injury

Objective To examine the relationship between birth weight and brachial plexus injury and estimate the number of cesareans needed to reduce such injuries. Methods All 80 neonatal records coded for brachial plexus injury from October 1985 to September 1993 at the Brigham and Womens Hospital in Boston, Massachusetts, were studied along with linked maternal files. Birth weight, method of delivery, presence or absence of shoulder dystocia, and any diagnosis of maternal gestational or nongestational diabetes were abstracted. Data for the group with brachial plexus injury were compared with data for live-born infants without this injury during the same period. The sensitivity and specificity of birth weight as a predictor of brachial plexus injury were calculated. Further, the number of cesarean deliveries necessary to prevent a single brachial plexus injury was estimated using various weight cutoffs (4000, 4500, and 5000 g) for elective cesarean delivery. Results Among 77,616 consecutive deliveries, there were 80 brachial plexus injuries identified, for an incidence of 1.03 per 1000 live births. The incidence of brachial plexus injury increased with increasing birth weight, operative vaginal delivery, and the presence of glucose intolerance. In the group of women without diabetes, between 19 and 162 cesarean deliveries would have been necessary to prevent a single immediate brachial plexus injury. Among women with diabetes, between five and 48 additional cesareans would have been required. Conclusion Although birth weight is a predictor of brachial plexus injury, the number of cesarean deliveries necessary to prevent a single injury is high at most birth weights. Because of the large number of cesarean deliveries needed to prevent a single brachial plexus injury in infants born to women without diabetes, it is difficult to recommend routine cesarean delivery for suspected macrosomia in these women.

The relationship between calcium intake and pregnancy-induced hypertension: Up-to-date evidence

In 1980 we pointed to a relationship between calcium intake and pregnancy-induced hypertension. The original epidemiologic observations showed an inverse association between calcium intake and incidence of eclampsia after adjusting by several confounding factors. A series of recent randomized clinical trials have demonstrated a reduction in blood pressure with calcium supplementation in animals, in healthy and mildly hypertensive subjects, and in pregnant women. It is hypothesized that parathyroid hormone plays a role since it is affected by calcium intake and can partially regulate the concentration of free cytosolic ionized calcium, thus triggering smooth muscle contraction. Randomized clinical trials showing a reduction in the incidence of pregnancy-induced hypertension with calcium supplementation have not as yet been published. However, preliminary observations appear to support this hypothesis.

Rate of uterine rupture during a trial of labor in women with one or two prior cesarean deliveries

OBJECTIVE We sought to determine whether there is a difference in the rate of symptomatic uterine rupture after a trial of labor in women who have had 1 versus 2 prior cesarean deliveries. STUDY DESIGN The medical records of all women with a history of either 1 or 2 prior cesarean deliveries who elected to undergo a trial of labor during a 12-year period (July 1984-June 1996) at the Brigham and Womens Hospital were reviewed. Rates of uterine rupture were compared for these 2 groups. Potential confounding variables were controlled by using logistic regression analyses. RESULTS Women with 1 prior cesarean delivery (n = 3757) had a rate of uterine rupture of 0.8%, whereas women with 2 prior cesarean deliveries (n = 134) had a rate of uterine rupture of 3.7% (P =.001). In a logistic regression analysis that was controlled for maternal age, use of epidural analgesia, oxytocin induction, oxytocin augmentation, the use of prostaglandin E(2) gel, birth weight, gestational age, type of prior hysterotomy, year of trial of labor, and prior vaginal delivery, the odds ratio for uterine rupture in those patients with 2 prior cesarean deliveries was 4.8 (95% confidence interval, 1.8-13. 2) CONCLUSIONS Women with a history of 2 prior cesarean deliveries have an almost 5-fold greater risk of uterine rupture than those with only 1 prior cesarean delivery.

Interdelivery interval and risk of symptomatic uterine rupture

Objective To relate interdelivery interval to risk of uterine rupture during a trial of labor after prior cesarean delivery. Methods We reviewed the medical records of all women who had a trial of labor after cesarean delivery over 12 years (July 1984 to June 1996). Analysis was limited to women with only one prior cesarean delivery and no prior vaginal deliveries who delivered term singletons and whose medical records included the month and year of the prior delivery. The time in months between the prior cesarean delivery and the index trial of labor was calculated, and the women were divided accordingly to permit comparison with respect to symptomatic uterine rupture. Results Two thousand four hundred nine women had trials of labor after one prior cesarean delivery and had complete data from the medical records. There were 29 uterine ruptures (1.2%) in the population. For interdelivery intervals up to 18 months, the uterine rupture rate was 2.25% (seven of 311) compared with 1.05% (22 of 2098) with intervals of 19 months or longer (P = .07). Multiple logistic regression was used to assess the risk of uterine rupture according to interdelivery interval while controlling for maternal age, public assistance, length of labor, gestational age at least 41 weeks, and oxytocin use. Women with interdelivery intervals of up to 18 months were three times as likely (95% confidence interval, 1.2, 7.2) to have symptomatic uterine rupture. Conclusion Interdelivery intervals of up to 18 months were associated with increased risk of symptomatic uterine rupture during a trial of labor after cesarean delivery compared with that for longer interdelivery intervals.

Effect of fat and fat-free mass deposition during pregnancy on birth weight.

OBJECTIVES The purposes of our study were to describe the patterns and location of fat and fat-free mass deposition during pregnancy and to evaluate their effects on fetal growth. STUDY DESIGN Our study is a prospective follow-up of 105 healthy pregnant women who were delivered of term infants. Body composition was evaluated eight times during gestation with anthropometric measures and bioimpedance techniques. Body fat and fat-free mass were calculated with equations specifically developed for this population. RESULTS Total weight gain was 10.0 +/- 3.5 kg; net weight gain was 3.7 +/- 0.31 kg; birth weight was 3211 +/- 467 gm (values are mean +/- SEM). In these women fat was deposited mostly in the thigh and subscapular region for a total of 6.23 +/- 0.19 kg at term. The period of pregnancy of the largest maternal fat deposition per week is between the twentieth and thirtieth weeks. After adjusting by prepregnancy weight, birth weight is associated with maternal changes in thigh skin folds and fat gain before the thirtieth week of gestation. Infants born to mothers with low fat gain before the thirtieth week were 204 gm lighter than infants born to mothers with fat gain > or = 25th percentile of this population. CONCLUSION Maternal nutritional status at the beginning of gestation and the rate of fat gain early in pregnancy are the two nutritional indicators most strongly associated with fetal growth in this population.

Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations

Results are presented of a randomized, double-blinded controlled clinical trial of calcium supplementation (2.0 gm of elemental calcium as calcium carbonate) and a placebo. All participants were 17 years of age or less and clinically healthy. Patients were enrolled by the twenty third week of gestation. The mean duration of calcium supplementation or placebo was approximately 14 weeks. Treatment consisted of 2.8 (+/- 1.5) tablets per day in the placebo group (N = 95) and 3.0 (+/- 1.4) tablets per day in the calcium group (N = 94). Dietary calcium intake was similar in both groups at about 1200 mg/day. The calcium group had a lower incidence of preterm delivery (less than 37 weeks; 7.4% vs 21.1%; p = 0.007); spontaneous labor and preterm delivery (6.4% vs 17.9%; p = 0.01); and low birth weight (9.6% vs 21.1%; p = 0.03). This effect was also present after stratified analysis by level of treatment compliance, urinary tract infection, and chlamydial infection. Life-table analysis demonstrated an overall shift to a higher gestational age in the calcium group compared with the placebo group (log-rank test, p = 0.02). As suggested previously, the observed effect could be mediated by a reduction in uterine smooth muscle contractibility. If confirmed by future research, these results could represent an important preventive intervention for prematurity in high-risk populations.

Elevated serum human chorionic gonadotropin as evidence of secretory response in severe preeclampsia

OBJECTIVE Because preeclampsia is a trophoblastic disorder and human chorionic gonadotropin is secreted from trophoblast, we sought to determine whether measurement of serum human chorionic gonadotropin might reflect a different trophoblastic secretory response of preeclampsia. STUDY DESIGN Twenty patients with mild preeclampsia and 12 with severe preeclampsia were matched with 32 healthy, normotensive women in the third trimester with singleton pregnancies. Serum total human chorionic gonadotropin and total human chorionic gonadotropin-beta were measured by a two-site immunoenzymometric assay, and total hCG-alpha was determined by a double-antibody radioimmunoassay. Wilcoxon signed-rank and Mann-Whitney rank-sum tests were used for statistical analysis. RESULTS Serum total human chorionic gonadotropin, total human chorionic gonadotropin-alpha, and total human chorionic gonadotropin-beta levels were significantly higher in severely preeclamptic women (p < 0.05), but not in those with mild preeclampsia, compared with those in their matched controls. CONCLUSION Elevated serum human chorionic gonadotropin levels in severely preeclamptic women might reflect a significantly pathologic change and secretory reaction of the placenta.

Acute complications of preeclampsia

Preeclampsia is an idiopathic multisystem disorder specific to human pregnancy and the puerperium. More precisely, it is a disease of the placenta, because it has also been described in pregnancies where there is trophoblast but no fetal tissue (complete molar pregnancies). Although the pathophysiology of preeclampsia is poorly understood, it is clear that the blueprint for its development is laid down early in pregnancy. It has been suggested that the pathologic hallmark is a complete or partial failure of the second wave of trophoblast invasion from 16 to 20 weeks’ gestation, which is responsible in normal pregnancies for destruction of the muscularis layer of the spiral arterioles. As pregnancy progresses, the metabolic demands of the fetoplacental unit increase. However, because of the abnormally shallow invasion of the placenta, the spiral arterioles are unable to dilate to accommodate the required increase in blood flow, resulting in “placental dysfunction” that manifests clinically as preeclampsia. Although attractive, this hypothesis remains to be validated. Preeclampsia is a clinical diagnosis. The classic definition of preeclampsia encompasses three elements: new-onset hypertension (defined as a sustained sitting blood pressure !140/90 mm Hg in a previously normotensive woman); new-onset proteinuria (defined as >300 mg/24 hours or !2+ on a clean-catch urinalysis in the absence of urinary tract infection); and new-onset significant nondependent edema. However, more recent consensus reports have suggested eliminating edema as a criterion for the diagnosis. A more extensive synopsis of preeclampsia is beyond the scope of this discussion. This monograph serves to review in detail the diagnosis and management of several acute maternal complications of preeclampsia: eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, liver rupture, pulmonary edema, renal failure, disseminated intravascular coagulopathy (DIC), hypertensive emergency, and hypertensive encephalopathy and cortical blindness. Correspondence: Errol R. Norwitz, MD, PhD, Department of Obstetrics & Gynecology, Brigham & Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. E-mail: enorwitz@partners.org PROD. # GRF20214