Cervical conization and the risk of preterm delivery

The current body of literature concerning cervical conization and its effect on subsequent pregnancy outcome is conflicting. Depending on the type of conization procedure that is examined and the quality of the control group, the results and conclusions vary widely. Because treatment for cervical intraepithelial neoplasia is commonplace among women of reproductive age, it is imperative that practitioners have an understanding of the issues surrounding the treatment. Therefore, this review will summarize the published literature that addresses excisional procedures of the uterine cervix and the risk of preterm delivery in subsequent pregnancies and provide reasonable treatment recommendations for women with cervical abnormalities and a desire for future fertility.     

Recurrent preterm birth

Recurrent preterm birth is frequently defined as two or more deliveries before 37 completed weeks of gestation. The recurrence rate varies as a function of the antecedent for preterm birth: spontaneous versus indicated. Spontaneous preterm birth is the result of either preterm labor with intact membranes or preterm prelabor rupture of the membranes. This article reviews the body of literature describing the risk of recurrence of spontaneous and indicated preterm birth. Also discussed are the factors which modify the risk for recurrent spontaneous preterm birth (a short sonographic cervical length and a positive cervicovaginal fetal fibronectin test). Patients with a history of an indicated preterm birth are at risk not only for recurrence of this subtype, but also for spontaneous preterm birth. Individuals of black origin have a higher rate of recurrent preterm birth.     

Cervical length,risk factors,and delivery outcomes among women with spontaneous preterm birth

Objectives: To evaluate differences in risk factors and delivery outcomes among women with spontaneous preterm birth (sPTB) with short (≤25?mm) versus normal (>25?mm) cervical length (CL).

Methods: Secondary analysis of a prospective cohort study of singleton gestations between 18 0/7 and 23 6/7 weeks, without prior sPTB, undergoing universal transvaginal CL screening between 1 January 2012 and 31 December 2013. Only women with sPTB (<37 0/7 weeks) were included. Demographic characteristics, risk factors for sPTB, delivery outcomes and presentation of PTB were collected. The primary outcome was mean number of risk factors.

Results: The cohort included 2071 women, of which 145 (7%) had PTB and 84 (4%) had sPTB. Sixty-nine (82%) women with sPTB had a CL >25?mm and 15 (18%) had a CL≤25?mm. Women with a short CL did not differ from women with normal CL with respect to demographic variables or mean number of risk factors (4.20?±?2.11 versus 3.52?±?1.97, p?=?0.23), but they did deliver at a significantly earlier gestational age (25.0?±?1.1 versus 34.6?±?3.1 weeks, p?<?0.01). The distribution of the presentation of sPTB was different in women with a short versus normal CL (p?<?0.01).

Conclusions: Among women with sPTB, women with a short CL had similar number of risk factors, but were more likely to deliver at a significantly earlier gestational age. A short CL identifies women at risk for very early sPTB.     

Short interpregnancy interval increases the risk of preterm premature rupture of membranes and early delivery

Objectives: Preterm premature rupture of membranes (PPROM) is a major contributor to overall preterm birth (PTB) rates. A short interpregnancy interval (IPI) is a well-known risk factor for PTB. It is unknown if a short IPI specifically affects the risk of developing PPROM in a subsequent pregnancy. We sought to determine the association between IPI and the risk of PPROM in a subsequent pregnancy.

Methods: A retrospective cohort study using the Missouri birth certificate database of singleton births from 2003 to 2013 was conducted. A short IPI (delivery of the prior pregnancy to conception of the index pregnancy) was defined as ≤6 months. IPI >6 months was categorized into two groups: IPI 7–23 months and IPI ≥24 months. PPROM was defined as premature rupture of membranes between 16⁰ and 36⁶ weeks. Multivariable logistic regression was conducted to determine the association between IPI and PPROM while controlling for maternal age, race, body mass index (BMI), education level, use of social services (Medicaid insurance, food stamps, or participation in the WIC [Women, Infants, and Children] program), tobacco use, and history of PTB. Secondary outcome included the gestational age at delivery, categorized into five subgroups (≤24⁰, 24¹?28⁰, 28¹?32⁰, 32¹?34⁰, and 34¹?36⁶ weeks).

Results: 474,957 subjects with singleton gestations had data available to calculate the IPI. Of these, 1.4% (n?=?6797) experienced PPROM. IPI ≤6 months was significantly associated with an increased risk of developing PPROM compared with patients with IPI ≥24 months (odds ratio (OR) 1.80, 95% CI 1.70–1.90, p?1 and 32⁰ weeks compared to the other two IPI groups (27.0 versus 15.0 and 16.4%, p?2, BMI ≥30?kg/m², use of social services, tobacco use, and a prior PTB.

Conclusion: Our data demonstrate that an IPI of ≤6 months is significantly associated with an increased risk of developing PPROM in the subsequent pregnancy. Of greater clinical relevance is that these women were more likely to deliver between 28¹ and 32⁰ weeks as compared with women with a longer IPI. Novel to this study is the establishment of a specific link between a short IPI and PPROM with subsequent early delivery. Several maternal demographic factors known to be associated with PTB risk were also found to be associated with an increased risk of PPROM. Further studies are necessary to elucidate plausible biologic mechanisms ultimately leading to the development and implementation of preventive and therapeutic strategies for this high-risk cohort.     

Elevated maternal serum-free β-human chorionic gonadotropin (β-hCG) and reduced risk of spontaneous preterm delivery*

Objective: To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD).

Study design: This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded.

Results: Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD.

Conclusions: High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.     

Interleukin-6 bedside testing in women at high risk of preterm birth

Objective. Infection is likely to contribute to preterm birth (PTB). Laboratory analysis has demonstrated that vaginal IL-6 is correlated with PTB. We aimed to investigate a bedside test in this context.

Method.?Vaginal secretions were collected from 71 asymptomatic high-risk women. After 20 minutes incubation at room temperature, samples were analyzed by the bedside reader (IL-6 concentration in pg/ml) (Milenia-Biotec, Germany). Maternal and neonatal infectious markers and pregnancy outcome were recorded.

Results.?IL-6 was related to PTB, latency to gestation and maternal infection but not neonatal infection. In women with visible fetal membranes (n?=?13), all of those with a high IL-6 (≥56 pg/ml) had a PTB (n?=?11) compared to half (n?=?1) with a low IL-6 (<56 pg/ml). All the women with a high IL-6 at?<24 weeks' (n?=?10) delivered before viability compared to none with a low IL-6 (n?=?2). In women with preterm prelabor rupture of membrane (PPROM) and high IL-6 (n?=?8) there was a trend toward more extreme PTB's (57% vs. 0%, p?=?0.19) and delivery within 7 days (71% vs. 50%, p?=?0.09) compared to low IL-6 (n?=?5).

Conclusion.?IL-6 may be useful in guiding the difficult management of patients with visible membranes and PPROM, for example, the potential benefit of a cervical cerclage.     

Risk for spontaneous preterm birth among inter-racial/ethnic couples*

Objective: Approximately 10% of US couples are inter-racial/ethnic. Substantial variation in preterm birth (PTB) rates is seen when stratified by race/ethnicity, although most studies focused solely on maternal racial/ethnic demographics. Our aims were to analyze the contribution of paternal in addition to maternal race/ethnicity, and to evaluate risk of spontaneous PTB for previously understudied inter-racial/ethnic couples.

Methods: California singleton live births from 2007 to 2010 were included. Race/ethnicity was determined based on self-report, obtained from birth certificates and defined as African American (AA), Hispanic, Asian, and White. Logistic regression was used to estimate odds ratios of spontaneous PTB at 20–23, 24–31, 32–36 and <37 weeks of gestation, with White–White couples as reference. Results were stratified by previous PTB, pre-gestational and gestational diabetes and hypertension. To investigate the paternal contribution to the risk for any given maternal race/ethnicity we assessed the rates of PTB among inter-racial/ethnic couples compared to the respective same-race couple. Odds ratios were adjusted for maternal age, parity, BMI, prenatal care, payor status, education and smoking.

Results: Among 1,664,939 live births, 13% (n?=?216,417) were born to inter-racial/ethnic couples. Compared to White–White couples, risk for spontaneous PTB was increased across all inter-racial/ethnic couples with a non-White mother, except when the father was Asian. Patterns of association were similar after stratification by previous PTB, hypertension and diabetes. Paternal race/ethnicity was also a significant risk factor for PTB.

Conclusions: Increased risks for spontaneous PTB were seen in most inter-racial/ethnic couple groupings. In addition to maternal race/ethnicity, paternal race/ethnicity was a significant risk factor in many inter-racial/ethnic couplings. Identifying such different risk profiles based on both maternal and paternal race/ethnicity may offer new lines of research inquiry for the underlying etiologies of PTB.     

Pregnancy after periviable birth: making the case for innovative delivery of interpregnancy care*

Objective: Women who have had a spontaneous periviable delivery are at high risk for recurrent preterm delivery. The objective of our study was to determine interpregnancy interval (IPI) after periviable birth as well as percentage of women taking 17 alpha hydroxyprogesteronecaproate (17OHP-C) after periviable birth. We then examined the association between adherence with a postpartum visit after a periviable birth and IPI as well as receipt of 17OHP-C.

Materials and methods: We included all women with a periviable delivery (20–26-week gestation) due to spontaneous preterm birth at Magee Women’s Hospital between 2009 and 2014, who had their subsequent delivery at our institution during or before May of 2016. Information on maternal, fetal, and neonatal outcomes was obtained from the Magee Obstetrical Medical and Infant (MOMI) database as well as chart abstraction. We calculated IPI, proportion of women who received 17OHP-C in their next pregnancy, and attendance rates with a postpartum visit. The relationship between attendance with a postpartum visit and IPI, and receipt of 17OHP-C was examined with a logistic regression.

Results: During the study period, 361 women had a spontaneous periviable birth. A total of 60 women had a subsequent delivery at Magee Women’s Hospital. Only 33/60 (52.5%) presented for a postpartum visit after their periviable delivery. The median IPI for the cohort was 12.5 months (interquartile range: 6.4, 17.5 months) and 21.0% (n?=?13) had an IPI less than 6 months. Adherence with the postpartum visit was not associated with an IPI less than 6 months. A total of 18.33% (11 women) did not receive 17OHP-C in their subsequent pregnancy. Women who attended a postpartum visit were much more likely to receive 17OHP-C (p?=?.001).

Conclusions: Many women with a history of a periviable birth do not optimize strategies to reduce their risk of recurrent preterm birth. While attendance with a postpartum visit was associated with greater receipt of 17OHP-C in the subsequent pregnancy, given the overall poor rate of attendance with the postpartum visit in this cohort, novel strategies to counsel women about interpregnancy health are needed.     

Adenomyosis and risk of preterm delivery

OBJECTIVE: To evaluate the risk of preterm delivery in patients with adenomyosis. DESIGN: A 1:2 nested case-control study. SETTING: Tertiary-care institution. POPULATION: A base cohort population of 2138 pregnant women who attended routine prenatal check-up between July 1999 and June 2005. METHODS: From this base cohort population, gravid women with singleton pregnancy who delivered prior to the completion of 37 weeks of gestation were identified and formed the study group. Singleton gravid women who had term delivery and who matched with age, body mass index, smoking, and status of previous preterm delivery were recruited concurrently and served as control group. Preterm delivery cases were further divided into spontaneous preterm delivery and preterm premature rupture of membranes (PPROM) cases. MAIN OUTCOME MEASURES: Risk analysis of preterm delivery between gravid women with and without adenomyosis. RESULTS: One-hundred and four preterm delivery case subjects and 208 control subjects were assessed. Overall, gravid women with adenomyosis were associated with significantly increased risk of preterm delivery (adjusted odds ratio 1.96, 95% CI 1.23-4.47, P=0.022). For subgroup analysis, gravid women with adenomyosis had an adjusted 1.84-fold risk of spontaneous preterm delivery (95% CI 1.32-4.31, P=0.012) and an adjusted 1.98-fold risk of PPROM (95% CI 1.39-3.15, P=0.017). CONCLUSIONS: Gravid women with adenomyosis were associated with increased risk of both spontaneous preterm delivery and PPROM. A common pathophysiological pathway may exist in these two disorders. Further in-depth biochemical and molecular studies are necessary to explore this phenomenon.     

Risk factors for cerebral palsy in PPROM and preterm delivery with intact membranes*

Objective: Gestational age (GA) at delivery and spontaneous prematurity are independent risk factors for cerebral palsy (CP). The aim of this study is to investigate perinatal risk factors for CP in spontaneous preterm delivery.

Methods: A retrospective cohort study of all single pregnancies complicated by spontaneous preterm labor (PTL) or PPROM with delivery at <34 weeks from January 2006 to December 2012 was performed. We compared demographic, obstetric, neonatal, and placental histology variables in cases of spontaneous preterm birth in reference to the development of CP. Statistical analysis included chi-square, one-way ANOVA and logistic regression analysis. p?<?0.05 was considered significant.

Results: Two hundred sixty-one women were included for this study. Of 249 survivors, 5 babies died during the first year of life, 52 did not fulfill the inclusion criteria for neurologic follow-up, and 24 were lost to follow up. Thus 168 infants in the study cohort underwent neurologic follow-up. We observed 26 cases of CP. Factors related to CP were lower GA at PROM (p?=?0.007) and longer latency from PPROM to delivery (p?=?0.002) in the PPROM group, lower GA at delivery (p?<?0.001) and presence of funisitis (p?<0.001) in the PTL group.

Conclusions: GA at membrane rupture in PPROM and GA at delivery in PTL are significantly associated with CP. A process leading to neurological damage may be initiated at the moment of membranes rupture in cases of PPROM and at the time of PTL in the group with intact membranes.     

Association between antenatal corticosteroids and neonatal hypoglycemia in indicated early preterm births*

Purpose: We sought to determine if administration of antenatal corticosteroids in early preterm births (<34 weeks) is associated with an increased risk of developing neonatal hypoglycemia (<40?mg/dL) within the first 48?h of neonatal life.

Materials and methods: Retrospective cohort of all indicated singleton preterm births (23?34 weeks) in a single tertiary center from 2011 to 2014. The primary outcome was neonatal hypoglycemia (<40?mg/dL) within the first 48?h of life. The outcome was compared by antenatal corticosteroids received at any point during the gestation, within 2–7 d of delivery, and whether the patient received a partial, full, or repeat course of antenatal corticosteroids. Logistic regression was used to adjust for confounders.

Results: Six hundred thirty-five patients underwent an indicated preterm birth during the study period. Six hundred and four (95%) received antenatal corticosteroids prior to delivery and 31 (5%) did not. The incidence of neonatal hypoglycemia within 48?h of life was not significantly different between those who received any antenatal corticosteroids and those who did not (23.0 versus 16.1%, adjusted odds ratio [OR] 1.3, 95%CI 0.5–3.6). Infants who received a full antenatal corticosteroid course within 2–7 d of delivery had similar incidences of hypoglycemia compared with those who received antenatal corticosteroids more than 7?d before delivery (20.4 versus 25.4%, adjusted OR 1.5, 95% confidence interval(CI) 0.8–2.9). Neonatal hypoglycemia was not increased by the number of antenatal corticosteroid doses (partial, full, or repeat course) administered. There was not a correlation between timing of antenatal corticosteroid administration before delivery, up to 250?h, and the lowest neonatal blood sugar in the first 48?h of life.

Conclusion: Our findings suggest antenatal corticosteroid administration in indicated early preterm infants (<34 weeks) may not increase the risk of developing neonatal hypoglycemia within the first 48?h of life. Further studies should validate our findings.