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.

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.

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.

Final results from the Betaseron (interferon ß-1b) Pregnancy Registry: a prospective observational study of birth defects and pregnancy-related adverse events.

OBJECTIVE: Women with multiple sclerosis are often diagnosed and treated during their reproductive years. Limited data are available on the safety of treatment during pregnancy. The Betaseron Pregnancy Registry prospectively monitored women exposed to interferon ß-1b (IFNß-1b) during pregnancy to estimate the rates of birth defects, spontaneous abortions (SABs) and other negative outcomes in this population. DESIGN: From 2006 to 2011, this observational registry enrolled women exposed prior to conception or during pregnancy (but prior to or without abnormalities on prenatal screening). Follow-up continued from enrolment through the 4-month paediatric visit. SETTING: Patients in the USA who met these criteria were enrolled in the registry. RESULTS: The registry enrolled 99 pregnant women; 3 were lost to follow-up. The earliest exposure to IFNß-1b occurred during the first trimester for 95 pregnancies and in the third trimester for 1 pregnancy. There were 99 birth outcomes (3 twins), including 86 (86.9%) live births, 11 (11.1%) SABs and 2 (2%) stillbirths. Birth defects were reported in five (5.1%) cases. Rates of birth defects and SAB were not significantly different from population comparators. No developmental concerns were identified at the 4-month paediatric visit. CONCLUSIONS: The small sample size limits the ability to draw definitive conclusions; however, there was no pattern to suggest increased negative outcomes with IFNß-1b. CLINICAL TRIALS REGISTRATION NUMBER: NCT00317564.

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.

Physical activity and maternal-fetal circulation measured by Doppler ultrasound.

OBJECTIVE: To examine the association of physical activity on maternal-fetal circulation measured by uterine and umbilical artery Doppler flow velocimetry waveforms. STUDY DESIGN: Participants included 781 pregnant women with Doppler ultrasounds of the uterine and umbilical artery and who self-reported past week physical activity. Linear and generalized estimating equation regression models were used to examine these associations. RESULT: Moderate-to-vigorous total and recreational activity were associated with higher uterine artery pulsatility index (PI) and an increased risk of uterine artery notching as compared with reporting no total or recreational physical activity, respectively. Moderate-to-vigorous work activity was associated with lower uterine artery PI and a reduced risk of uterine artery notching as compared with no work activity. No associations were identified with the umbilical circulation measured by the resistance index. CONCLUSION: In this epidemiologic study, recreational and work activity were associated with opposite effects on uterine artery PI and uterine artery notching, although associations were modest in magnitude.

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.

Impact of maternal malaria and under-nutrition on intrauterine growth restriction: a prospective ultrasound study in Democratic Republic of Congo.

Maternal malaria and under-nutrition are established risk factors for small-for-gestational-age (SGA) births; however, whether malaria is associated with intrauterine growth restriction (IUGR) is unknown. We investigated IUGR risk among 177 HIV-negative pregnant women enrolled in a longitudinal ultrasound study conducted in Democratic Republic of Congo from May 2005 to May 2006. Malaria infection, maternal anthropometrics, and ultrasound estimated fetal weight were measured monthly. All positive malaria cases were treated and intermittent presumptive therapy (IPTp) provided. Log-binomial regression models for IUGR were fitted using generalized estimating equations to account for statistical clustering of repeat IUGR measurements. Twenty-nine percent of fetuses experienced an episode of IUGR with the majority occurring in the third trimester. The risk of IUGR associated with malaria was greatest after three or more cumulative infections (RR 3.3, 95% CI 1.3-8.2) and was two- to eight-fold higher among women with evidence of under-nutrition. Receiving antimalarial treatment in the previous month (for IPTp or treatment) was significantly protective against IUGR (RR 0.5, 95% CI 0.3-0.7). The interaction observed between malaria and under-nutrition suggests that antenatal programmes in malaria endemic areas should incorporate nutritional screening and supplementation in addition to IPTp.

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.

Psychological and biological markers of stress and bacterial vaginosis in pregnant women.

OBJECTIVES: To determine whether stress is associated with risk of bacterial vaginosis (BV) in pregnant women. DESIGN: Prospective cohort study. SETTING: The prenatal care clinics at the University of North Carolina. The residents' clinic sees mostly government-insured and uninsured women, and the physicians' clinic sees mostly those with private health insurance. POPULATION: A total of 897 women gave samples for BV analysis. Study participants were 22% African-American, 68% white; 24% unmarried and 44% nulliparous. More than half had completed college. METHODS: Women completed two questionnaires and two interviews reporting stress and psychological aspects of their lives. Measurement scales included the Sarason life events questionnaire, the Cohen perceived stress scale, Spielberger state-trait anxiety, the John Henryism coping style and the Medical Outcomes Study social support inventory. Two stress hormones, corticotrophin-releasing hormone and cortisol, were also measured. MAIN OUTCOME MEASURES: BV at 15-19 and 24-29 weeks of gestation was diagnosed by Gram's stain. RESULTS: Women in the highest quartile of stress measures, particularly state anxiety (OR=2.0, 95% CI 1.2-3.3), perceived stress (OR=2.4, 95% CI 1.5-3.9) and total life events (OR=2.0, 95% CI 1.3-3.2), had the highest risk of BV. Adjustment for confounders, especially age, race, and income, reduced these associations (state anxiety: OR=1.3, 95% CI 0.7-2.4; perceived stress: OR=1.4, 95% CI 0.8-2.5; total life events: OR=1.3, 95% CI 0.7-2.4). No clear pattern of association was seen between stress hormones and BV. CONCLUSIONS: Few associations between stress and BV were seen after adjustment for confounders.

Risk factors for preterm birth in Vietnam.

OBJECTIVE: To identify the risk of preterm birth and possible determinants among women in Hanoi, Vietnam. METHOD: Prospective cohort study of 1709 women with singleton live births at Hanoi Obstetrics and Gynecology Hospital, Hanoi, Vietnam, June-October 2002. Logistic regression analysis was used to examine predictors of preterm birth (<37 weeks' gestation). RESULT: The risk of preterm birth was 11.8%. Physically demanding work during pregnancy, two or more prior spontaneous abortions, history of preterm birth, vaginal bleeding, inadequate prenatal care during the first 20 weeks of gestation, and history of intrauterine device use with removal less than 12 months before the current pregnancy were associated with increased risk of preterm birth (adjusted odds ratios between 1.8 and 2.6). CONCLUSION: Preterm birth is relatively frequent in this population. Beyond established risk factors, these data implicated agricultural work and physical work demands with preterm birth, as well as history of recent IUD use.

Could ultrasonography be used by an anaesthetist to identify a specified lumbar interspace before spinal anaesthesia?

BACKGROUND: Insertion of a needle into the lumbar subarachnoid space may cause damage to the spinal cord. Current techniques to identify a safe interspace have limitations. Ultrasound was investigated as a means to improve anatomical accuracy. METHODS: Seventeen patients attending for elective magnetic resonance imaging (MRI) of the spine were studied. Ultrasonic identification of the L3-4 interspace was attempted by an anaesthetist and a marker was placed. A radiologist identified the anatomical location of the marker on the MRI scan. RESULTS: Thirteen out of 17 markers were at the L3-4 interspace; four were at the L2-3 interspace. CONCLUSIONS: These results suggest that ultrasonography may be a useful adjunct to safe subarachnoid anaesthesia.

Altered expression of TCR-CD3zeta induced by sera from women with preeclampsia.

OBJECTIVE: To investigate TCR-CD3zeta expression by cultured T lymphocytes exposed to midtrimester sera from pregnant women in whom preeclampsia developed at term compared with normotensive pregnant control subjects. STUDY DESIGN: Sera obtained at 24 to 28 weeks' gestation from 16 nulliparous women in whom preeclampsia developed at term and from 32 gestational age-matched control subjects without preeclampsia were evaluated for TCR-CD3zeta chain expression with use of Jurkat cells. Subsets of serum samples from 6 women with preeclampsia and 6 control subjects were then evaluated for their ability to induce apoptosis and to suppress interleukin-2 production. Groups were compared by use of the Kruskal-Wallis test, and P <.05 was considered significant. RESULTS: TCR-CD3zeta chain expression in cultured T lymphocytes was suppressed in approximately 60% of untreated control subjects after incubation with sera from normotensive pregnant women compared with 30% after incubation with sera from women with preeclampsia (P <.001). T-cell apoptosis was significantly higher after incubation with sera from normotensive control subjects, as was the expression of the proapoptotic regulator Bax, compared with sera from women with preeclampsia. Interleukin-2 levels were higher in T cells incubated with sera from women in whom preeclampsia later developed compared with sera from normotensive pregnant women (27.7 ng/mL versus 72.5 ng/mL; P <.001). CONCLUSIONS: Nulliparous women in whom preeclampsia developed did not suppress TCR-CD3zeta levels to the extent of normotensive control subjects, which may be linked to decreased lymphocyte apoptosis. This occurs remotely from the manifestation of clinical disease and suggests a deficiency in a serum factor in preeclampsia that may induce T cell zeta chain suppression in normal pregnancy.