C. Andrew Combs

Risk factors for third-degree and fourth-degree perineal lacerations in forceps and vacuum deliveries

Third- and fourth-degree perineal lacerations occur frequently during operative vaginal deliveries. To identify risk factors for lacerations, 2832 consecutive forceps and vacuum extraction deliveries were analyzed. Third- and fourth-degree lacerations occurred in 30% of deliveries. Multiple logistic regression was used to control for intercorrelation between potential risk factors. Factors associated with increased risk for third- and fourth-degree lacerations were midline episiotomy, nulliparity, second-stage arrest, occipitoposterior position, low or mid station, use of forceps instead of vacuum, use of local anesthesia, and Asian race. When these factors were controlled, there was no effect of birth weight, faculty versus resident operator, gestational age, abnormalities of first-stage labor, or several other factors. Prevention of perineal lacerations requires that the operator identify the patient at risk. Possible options for management of high-risk patients include use of mediolateral episiotomy or no episiotomy, use of vacuum extraction instead of forceps, and use of conduction anesthesia.

Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes

OBJECTIVE The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes. STUDY DESIGN Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL). RESULTS The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.2-11.2, OR, 3.1; 95% CI, 1.5-6.4, and OR, 1.8; 95% CI, 0.6-5.5, respectively). CONCLUSION We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.

Progression of diabetic retinopathy in pregnancy: association with hypertension in pregnancy.

OBJECTIVE To test the hypothesis that women with insulin-dependent diabetes and chronic or pregnancy-induced hypertensive disorders are at increased risk for developing retinopathic complications during pregnancy. STUDY DESIGN One hundred fifty-four women with insulin-dependent diabetes were prospectively followed in an intensive program of diabetes in pregnancy. Ophthalmologic evaluations were obtained through pregnancy and at 6 to 12 weeks post partum, and findings were graded by a standard scale. Association of retinopathic progression with risk factors was tested with chi 2 and multiple logistic regression analysis. RESULTS Fifty-one women had progression of retinopathy during pregnancy; postpartum regression was observed in 13 women. Changes in glycemic control early in pregnancy, chronic hypertension, and pregnancy-induced hypertension were significantly associated with progression of retinopathy. CONCLUSION Women with insulin-dependent diabetes who have hypertensive disorders in pregnancy are at increased risk for progression of retinopathy.

Experimental preeclampsia produced by chronic constriction of the lower aorta: validation with longitudinal blood pressure measurements in conscious rhesus monkeys.

OBJECTIVES Our goals were (1) to determine whether hypertension, proteinuria, and glomerular endotheliosis can be produced by chronic reduction of lower aortic pressure in pregnant rhesus monkeys and (2) to study the time course of the development of hypertension by means of longitudinal arterial blood pressure measurements in conscious, unrestrained pregnant rhesus monkeys. STUDY DESIGN Indwelling arterial catheters were placed at 103 +/- 4 days of gestation (term 160 days) for measurement of arterial pressure before and after reduction of lower aortic pressure. At 116 +/- 7 days lower aortic pressure was reduced by 24 +/- 11 mm Hg in 11 monkeys (experimental group) by a stricture on the aorta just below the renal arteries; six monkeys (controls) underwent a sham operation. Resting on the aorta just below the renal arteries; six monkeys (controls) underwent a sham operation. Resting pressures were measured three to five times per week by a tether-and-swivel system. RESULTS Baseline arterial pressure averaged 81 +/- 6 mm Hg. In the experimental group four monkeys had adverse outcomes (one maternal death with severe hypertension, one abruptio placentae with stillbirth, and two spontaneous preterm deliveries with hypertension). There was one preterm delivery in the control group. Of the seven monkeys with aortic stricture who continued to term, four developed sustained hypertension (mean pressure 18 +/- 6 mm Hg above baseline), proteinuria, and moderate-to-severe glomerular endotheliosis. None of the controls had hypertension or proteinuria, but two had endotheliosis. CONCLUSION These observations confirm that a syndrome resembling preeclampsia can be produced by a reduction of lower aortic pressure, and they demonstrate that the associated hypertension is not an artifact of anesthesia. This model may prove useful in studying the pathophysiologic mechanisms of preeclampsia.

17-hydroxyprogesterone caproate for twin pregnancy: a double-blind, randomized clinical trial.

OBJECTIVE We sought to determine whether prophylactic treatment with 17-alpha-hydroxyprogesterone caproate (17Pc) in twin pregnancy will reduce neonatal morbidity (primary outcome) by prolonging pregnancy (secondary outcome). STUDY DESIGN This was a double-blind, randomized clinical trial. Mothers carrying dichorionic-diamniotic twins were randomly assigned (in a 2:1 ratio) to weekly injections of 250 mg of 17Pc or placebo, starting at 16-24 weeks and continued until 34 weeks. RESULTS In all, 160 women were randomized to 17Pc and 80 to placebo. Composite neonatal morbidity occurred with similar frequency in the 17Pc and placebo groups (14% vs 12%, respectively, P = .62). Mean gestational age at delivery was not affected by 17Pc (35.3 vs 35.9 weeks, P = .10), but a 3-day difference in median gestational age favored placebo (P = .02). There were no perinatal deaths with 17Pc and 3 with placebo. CONCLUSION In twin pregnancy, prophylactic treatment with 17Pc did not prolong gestation or reduce neonatal morbidity.

Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet pregnancy: a double-blind randomized clinical trial

OBJECTIVE To test whether 17 alpha-hydroxyprogesterone caproate (17P) will reduce neonatal morbidity by increasing gestational age at delivery in triplet pregnancies. STUDY DESIGN Double-blind, randomized clinical trial. Mothers carrying trichorionic-triamniotic triplets were randomly assigned (in a 2:1 ratio) to weekly injections of 250 mg of 17P or placebo, starting at 16-22 weeks and continued until 34 weeks. Primary outcome was composite neonatal morbidity. RESULTS Fifty-six women were randomized to 17P and 25 to placebo. Composite neonatal morbidity occurred with similar frequency in the 17P and placebo groups (38% vs 41%, respectively; P = .71). Mean gestational age at delivery was not affected by 17P (31.9 vs 31.8 weeks; P = .36). There were 13 midtrimester fetal losses with 17P vs none with placebo (P < .02). CONCLUSION In triplet pregnancy, prophylactic treatment with 17P did not reduce neonatal morbidity or prolong gestation but was associated with increased midtrimester fetal loss.

Increased depth of trophoblast invasion after chronic constriction of the lower aorta in rhesus monkeys

OBJECTIVE Our purpose was to investigate whether a reduction in uteroplacental perfusion pressure would produce changes in trophoblast-uterine interactions at the cellular level. STUDY DESIGN Strictures were placed around the abdominal aortas of rhesus monkeys at 116 +/- 7 days of pregnancy to reduce uteroplacental perfusion pressure. Placental bed biopsy specimens were obtained at cesarean section, and cytotrophoblasts were identified by means of an anticytokeratin antibody. RESULTS In monkeys without aortic strictures, interstitial trophoblast invasion was restricted to the outer half of the endometrium. Endovascular trophoblast invasion involved the entire endometrial portion of uterine vessels and extended through the subjacent half of their myometrial segments. In seven of nine monkeys with aortic strictures the depth of interstitial trophoblast invasion was substantially increased and extended throughout the entire decidua and at least a portion of the myometrium. In contrast, the pattern of endovascular trophoblast invasion was identical to that observed in the placental beds of control animals. CONCLUSION These results suggest that uteroplacental perfusion pressure or oxygen content may be important physiologic factors controlling the depth of interstitial cytotrophoblast invasion.

DIABETIC NEPHROPATHY AND PREGNANCY

Knowledge of the pathogenic mechanisms of diabetic nephropathy (by which hyperglycemia, hyperfiltration, and hypertension cause the gradual development of microproteinuria, mesangial expansion, and eventual glomerular closure) provides the basis for effective treatment. Intensified glycemic control and antihypertensive therapy that is safe for the fetus are crucial for success during pregnancy. Considered outcome measures include perinatal survival, size at birth, child development, and long-term maternal renal function.

Urinary protein/creatinine ratio before and during pregnancy in women with diabetes mellitus

Quantitation of urinary protein excretion has traditionally involved collection of a 24-hour urine specimen. Recent reports have suggested that the ratio of protein to creatinine in a single-voided urine specimen may be used as a screening test of proteinuria, obviating the need for a 24-hour urine collection. This study was undertaken to determine whether the urinary protein/creatinine ratio was correlated with 24-hour protein excretion in women with diabetes, to determine whether pregnancy had any effect on the correlation, and to test the accuracy of estimates of 24-hour protein excretion on the basis of the protein/creatinine ratio. We studied 329 24-hour urine specimens from 133 women with classes B through RF diabetes. The protein/creatinine ratio was highly correlated with total protein excretion (r = 0.977, p less than 0.0001). The correlation was not affected by pregnancy, trimester, or preeclampsia. Three methods were used to predict protein excretion on the basis of the ratio. Compared with actual protein excretion, predicted values had mean errors of 19% to 27%; 6% to 13% of predictions were in error by greater than or equal to 50%. Because of these large errors, we conclude that this method of estimating protein excretion has limited value in pregnant women with diabetes.

Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis

Objective To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies. Design Systematic review and meta-analysis. Data sources Medline, Embase, and Cochrane databases (until December 2015). Review methods Databases were searched without language restrictions for studies of women with uncomplicated twin pregnancies that reported rates of stillbirth and neonatal outcomes at various gestational ages. Pregnancies with unclear chorionicity, monoamnionicity, and twin to twin transfusion syndrome were excluded. Meta-analyses of observational studies and cohorts nested within randomised studies were undertaken. Prospective risk of stillbirth was computed for each study at a given week of gestation and compared with the risk of neonatal death among deliveries in the same week. Gestational age specific differences in risk were estimated for stillbirths and neonatal deaths in monochorionic and dichorionic twin pregnancies after 34 weeks’ gestation. Results 32 studies (29 685 dichorionic, 5486 monochorionic pregnancies) were included. In dichorionic twin pregnancies beyond 34 weeks (15 studies, 17 830 pregnancies), the prospective weekly risk of stillbirths from expectant management and the risk of neonatal death from delivery were balanced at 37 weeks’ gestation (risk difference 1.2/1000, 95% confidence interval −1.3 to 3.6; I2=0%). Delay in delivery by a week (to 38 weeks) led to an additional 8.8 perinatal deaths per 1000 pregnancies (95% confidence interval 3.6 to 14.0/1000; I2=0%) compared with the previous week. In monochorionic pregnancies beyond 34 weeks (13 studies, 2149 pregnancies), there was a trend towards an increase in stillbirths compared with neonatal deaths after 36 weeks, with an additional 2.5 per 1000 perinatal deaths, which was not significant (−12.4 to 17.4/1000; I2=0%). The rates of neonatal morbidity showed a consistent reduction with increasing gestational age in monochorionic and dichorionic pregnancies, and admission to the neonatal intensive care unit was the commonest neonatal complication. The actual risk of stillbirth near term might be higher than reported estimates because of the policy of planned delivery in twin pregnancies. Conclusions To minimise perinatal deaths, in uncomplicated dichorionic twin pregnancies delivery should be considered at 37 weeks’ gestation; in monochorionic pregnancies delivery should be considered at 36 weeks. Systematic review registration PROSPERO CRD42014007538.