Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm.

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal vitamin C and E supplementation in smokers is associated with reduced placental abruption and preterm birth: a secondary analysis.

OBJECTIVE: Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking. DESIGN/SETTING/POPULATION: A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations. METHODS: We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction. MAIN OUTCOME MEASURES: The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption. RESULTS: There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046). CONCLUSION: In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers.

Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids.

OBJECTIVE: The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. RESULTS: CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

OBJECTIVE: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. DESIGN: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. SETTING: A multicentre study in 16 academic medical centres in the USA. POPULATION: Low-risk nulliparous women. METHODS: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. MAIN OUTCOME MEASURES: Change in PlGF, sFlt-1 and sEng. RESULTS: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. CONCLUSION: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.

Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women.

OBJECTIVE: To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. DESIGN: A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. SETTING: Fourteen academic health centres in the USA. POPULATION: Women with prior spontaneous preterm birth. METHODS: In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. MAIN OUTCOME MEASURES: Recurrent preterm birth at <37 and <32 weeks of gestation. RESULTS: The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). CONCLUSIONS: In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth.

Ultrasound-derived fetal size nomogram for a sub-Saharan African population: a longitudinal study.

OBJECTIVES: To create a fetal size nomogram for use in sub-Saharan Africa and compare the derived centiles with reference intervals from developed countries. METHODS: Fetal biometric measurements were obtained at entry to antenatal care (11-22 weeks' gestation) and thereafter at 4-week intervals from pregnant women enrolled in a longitudinal ultrasound study in Kinshasa, Democratic Republic of Congo. The study population comprised 144 singleton gestations with ultrasound-derived gestational age within 14 days of the menstrual estimate. A total of 755 monthly ultrasound scans were included with a mean +/- SD of 5 +/- 1 (range, 2-8) scans per woman. Estimated fetal weight (EFW) was calculated at each ultrasound examination using the Hadlock algorithm. A general mixed-effects linear regression model that incorporated random effects for both the intercept and slope was fitted to log-transformed EFW to account for both mean growth and within-fetus variability in growth. Reference centiles (5(th), 10(th), 50(th), 90(th) and 95(th) centiles) were derived from this model. RESULTS: Nomograms derived from developed populations consistently overestimated the 50(th) centile EFW value for Congolese fetuses by roughly 5-12%. Differences observed in the 10(th) and 90(th) centiles were inconsistent between nomograms, but generally followed a pattern of overestimation that decreased with advancing gestational age. CONCLUSIONS: In low-resource settings, endemic malaria and maternal nutritional factors, including low prepregnancy weight and pregnancy weight gain, probably lead to lower fetal weight and utilization of nomograms derived from developed populations is not appropriate. This customized nomogram could provide more applicable reference intervals for diagnosis of intrauterine growth restriction in sub-Saharan African populations.

Stress and placental resistance measured by Doppler ultrasound in early and mid-pregnancy.

OBJECTIVES: To examine the association between self reports and biomarkers of stress and placental resistance (measured by Doppler ultrasound of the uterine and umbilical arteries), to determine if restriction of blood flow to the placenta is a mechanism by which stress might affect health during pregnancy. METHODS: Eight hundred and seventy-two women had ultrasound examinations of the uterine artery at 15-19 weeks' gestation and the uterine and umbilical arteries at 24-29 weeks, and resistance and pulsatility indices were calculated. Psychosocial stress was measured by telephone interview and self-administered questionnaire using several validated tools twice during the pregnancy. Cortisol and corticotropin-releasing hormone (CRH) were measured twice during the pregnancy. Linear and hierarchical models were used to examine the relationships among reported stress, stress hormones and placental Doppler indices. RESULTS: The umbilical artery resistance index was higher in younger women, those with less education, those who were single and those who smoked. The uterine artery pulsatility index was higher in women with pre-eclampsia, those living alone, those with high body mass index, and those who gained the least weight during pregnancy. A higher CRH level was associated with small increases in uterine artery pulsatility and umbilical artery resistance indices. Psychosocial measures of stress were not consistently associated with higher placental resistance. CONCLUSIONS: Increased CRH levels may be associated with increased placental resistance. Otherwise, these findings do not support the hypothesis that restriction of blood flow to the fetus is a major mechanism by which stress affects infant health.

Low mortality from all causes, including myocardial infarction, in well-controlled hypertensives treated with a beta-blocker plus other antihypertensives.

The aim of the present study was to monitor the efficacy of treatment, morbidity and mortality over a 10-year period in 939 moderate to severe hypertensive patients. All patients were treated in the same hypertension clinic with the beta 1-selective agent atenolol, administered either alone or more usually with a diuretic with or without a vasodilator or other agents. Survival rates were compared with predicted survival rates, had the hypertension not been treated, and also with those of a local reference population matched for age and sex. After a mean follow-up time of 6.1 years, mean blood pressure (BP) was significantly lowered from 183/109 to 145/87 mmHg. Biochemical disturbance was minimal. There were 79 withdrawals from treatment, of whom 37 were lost to follow-up. There were 91 deaths on intention to treat. Systolic blood pressure (SBP) on treatment, and not initial BP, was a powerful predictor of mortality. Patients of all age groups with well-controlled SBP were less likely to die, particularly from myocardial infarction, than those with less well controlled SBP (P less than 0.001). However, due to possible J-curve relationships between treated BP and outcome, lowering SBP below 140-150 mmHg in the elderly, and the diastolic blood pressure (DBP) below about 85 mmHg, may not be beneficial. Total mortality and mortality due to myocardial infarction was about 60% [corrected], of predicted level, had a high BP not been treated, being similar to that in a local reference control population (age- and sex-matched). The death rate from stroke was reduced to about 50% of that predicted. Patients who died showed a mean fall in mean serum triglyceride concentration in contrast to the mean increase that occurred in survivors. It is concluded that patients with moderate to severe hypertension who obtain a high level of general health care and optimal control of BP for up to 10 years, experience a significant decrease in total mortality rate and death from myocardial infarction and stroke.

Determinants of hormone replacement therapy duration among postmenopausal women with intact uteri.

OBJECTIVE: To investigate factors associated with hormone replacement therapy (HRT) duration among postmenopausal women with intact uteri. DESIGN: A Cox proportional hazard model on time to HRT discontinuation is estimated for 2,632 postmenopausal HRT users with intact uteri who began a new episode of treatment between January 1990 and December 1994 in Saskatchewan, Canada. RESULTS: Major contraindicating medical events were highly associated with HRT discontinuation among postmenopausal women. Women who were diagnosed with uterine cancer while taking HRT were almost four times as likely to discontinue HRT, and women who were diagnosed with breast cancer while taking HRT were nearly five times as likely to discontinue HRT. Other statistically significant factors associated with the duration of HRT episodes include administration mode and the ability to try different types and strengths of HRT. Women initiating HRT with a transdermal patch were 50% more likely to discontinue it. Women who were willing and able to experiment with different HRT reduced their likelihood of discontinuing by one-half to three-fourths. CONCLUSIONS: Although some of the factors associated with the hazard of HRT discontinuation among postmenopausal women who are taking the treatment for preventive benefits are immutable, clinicians may influence HRT continuation rates through initial drug choice or modifications in drug type or regimen over the course of therapy.

Vaginal endosonography in the assessment of the anorectum.

Endosonography from within the anus has been used to image the anorectum and its associated musculature. A 5.0-MHz endovaginal probe was inserted vaginally, and longitudinal and cross-sectional views of the anorectum were obtained. We were able to measure rectal length and diameter, puborectalis thickness and angle, thickness of internal and external anal sphincter, and the curvature of the anal canal. We visualized defects in the internal and external anal sphincters. Suitable images were obtained from 70 subjects. Muscle thicknesses were within previously published ranges. Twenty-five of 70 subjects (36%) had defects of the internal anal sphincter, and 19 of 65 subjects (29%) had defects of the external anal sphincter.

FSH levels in relation to hysterectomy and to unilateral oophorectomy.

OBJECTIVE: To examine the association between hysterectomy, unilateral oophorectomy, and ovarian status, measured by FSH concentrations, in women aged 35-49 years. METHODS: From the National Health and Examination Survey III, 1716 women aged 35-49 years were studied. Information on menopausal status, surgical history (hysterectomy, single or bilateral oophorectomy), smoking, and other characteristics was collected in a structured interview, height and weight were measured, and one blood sample was collected. We used logistic regression to analyze FSH concentration in relation to hysterectomy and oophorectomy, controlling for age, ethnicity, body mass index, smoking, education, nulligravidity, and exercise. RESULTS: Hysterectomy with unilateral oophorectomy was associated with an increased prevalence of elevated FSH (above 20 IU/L) (adjusted odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3, 4.6) compared with women who had not had hysterectomies or oophorectomies. Among women with two ovaries, hysterectomy was associated with increased prevalence of elevated FSH (adjusted OR 1.5, 95% CI 1.0, 2.5). As a comparison of the effect size, the observed association between hysterectomy and elevated FSH was smaller than the association between FSH and current smoking (OR 2.0), a factor associated with a 1-2 year decrease in mean age at natural menopause. CONCLUSION: Although the differences in FSH levels were small, there was evidence of elevated FSH in women who have had hysterectomies, even if at least one ovary remained.

Ovarian suspension in massive ovarian edema.

Massive ovarian edema is an uncommon condition found in young women that is speculated to occur as a result of incomplete ovarian torsion. We present the second patient to our knowledge to undergo ovarian suspension as a treatment for this condition. This approach succeeded after ovarian wedge resection had failed. Our patient remained symptom-free at 1 year of follow-up. Ovarian suspension should be considered when this pathologic entity is diagnosed.

Utility of Leopold maneuvers in screening for malpresentation.

Malpresentation is a common complication of pregnancy. Using ultrasound as the gold standard, we prospectively tested Leopold maneuvers as a screen for nonvertex presentation in the third trimester. In our hands this technique performed poorly. Values for sensitivity, specificity, positive predictive value, and negative predictive value were 28, 94, 24, and 95%, respectively, in a population with a 7% prevalence of noncephalic presentation. Much of the correlation between the screening and diagnostic tests seemed to arise from chance (kappa = 0.13).

Selected use of midline episiotomy: effect on perineal trauma.

A prospective, nonrandomized controlled study was performed to determine the effect of using midline episiotomy only for mothers who experienced fetal distress and/or operative vaginal delivery. Such a policy resulted in a significant decline in third- and fourth-degree lacerations in nulliparous women. This reduction was most pronounced in nulliparous women delivering infants larger than 3400 g. No third- or fourth-degree laceration occurred without antecedent episiotomy in any woman. A policy of using episiotomy selectively appears to lower the incidence of perineal trauma.

Assessment of perineal floor function: electromyography with acrylic plug surface electrodes in nulliparous women.

A new technique using acrylic plug surface electrodes was employed to record electromyographic activity in the musculature surrounding the rectum and vagina. Forty-one asymptomatic nulliparous women were tested. The group had a wide range of normal values. When eight women were chosen at random for a second testing session, intra-class correlation coefficients to compare readings between the two sessions ranged from 0.76-0.97, indicating adequate reliability. No demographic factor correlated with the voltage generated in these women.

The Mueller-Hillis maneuver: can it be used to predict dystocia?

OBJECTIVE: To assess prospectively the utility of intrapartum Mueller-Hillis maneuvers in predicting labor abnormalities. METHODS: Patients underwent Mueller-Hillis maneuvers upon admission in active labor. Outcomes of each labor were assessed, and correlations were sought between the degree of descent and outcome. Labor curves were constructed for each patient, and labor abnormalities were described by an observer blinded to descent and outcome. The relationship of labor abnormality to outcome also was evaluated. RESULTS: One hundred six patients had Mueller-Hillis maneuvers performed. The distribution of results was as follows: no descent (N = 25) 23.6% one station (N = 33) 31.1%, two stations (N = 46) 43.4%, and three stations (N = 2) 1.9%. Lack of descent failed to indicate increased risk of abdominal delivery, operative vaginal delivery, need for oxytocin augmentation, prolonged second stage, or labor curve abnormality. Analysis of parity (nulliparous versus multiparous) did not alter these findings. CONCLUSION: We present normative data for the results of Mueller-Hillis maneuvers performed in active labor. To our knowledge, no such data exist. We also failed to find a relationship between dystocia and descent with the maneuver. Until this test is demonstrated to be useful, it should not be used to predict dystocia.