Determining Maternal Risk Factors and Biomarkers Associated with Preterm Birth: A Multicentric Cohort Study

Male sex is a risk factor for pre-term birth (PTB) among singleton pregnancies; however, in twin pregnancies, the effect of sex on PTB is not yet clear. The aim of this study was to evaluate the effect of twin's sex on risk of PTB. During this analytical cross-sectional study, we evaluated the effect of twin's sex, chorionicity and other factors on risk of PTB in 676 pregnant women in a university hospital in Tehran, Iran. Existence of male gender in pregnancy was a risk factor for PTB. Comparing same sex twins together, male–male gender was a risk factor for PTB (OR = 1.67 (1.19–2.34), p = 0.002), early PTB (OR = 1.18 (1.04–1.34), p = 0.01) and very early PTB (OR = 1.06 (1–1.13), p = 0.04). Monoamnion twins were at higher risk for early PTB (OR = 1.44 (1.08–1.92), p = 0.02), and very early PTB (OR = 1.95 (1.1–3.44), p = 0.03) but the risk did not increase in monochorion twins. History of abortion was also shown to be a risk factor (p < 0.05). Maternal age, multiparity, body mass index (BMI) and assisted reproductive techniques (ART) did not reach the significance levels to be considered as risk factors.

Challenges in defining and classifying the preterm birth syndrome

To evaluate whether a history of spontaneous early-term birth (37+0 -38+6 weeks of gestation) in the previous singleton pregnancy is a risk factor for preterm birth (PTB) in a subsequent twin pregnancy. Retrospective cohort study. Two French university hospitals (2006-2016). All women who delivered twins from 24+0 weeks after a preceding singleton pregnancy birth at 37+0 to 41+6 weeks. Multivariate logistic regression analysis of association between twin PTB and a previous spontaneous singleton early-term birth. Twin PTB rate before 37, 34 and 32weeks of gestation. Among 618 twin pregnancies, 270 were born preterm, 92 of them with a preceding spontaneous singleton early-term birth. The univariate analysis showed a significantly higher risk of twin PTB before 37, 34 and 32weeks among those 92 women compared with those with a full- or late-term birth in their previous singleton pregnancy. This association remained significant after logistic regression (odds ratio [OR] between 2.42 and 3.88). The secondary analysis, restricted to the twin pregnancies with spontaneous PTB found similar results, with a risk of PTB before 37, 34 and 32weeks significantly higher among women with a previous spontaneous singleton early-term birth, including after logistic regression analysis (OR between 3.51 and 3.56). A preceding spontaneous singleton early-term birth is a strong and easily identified risk factor for PTB in twin pregnancies. Spontaneous 'early-term' birth of a singleton is a significant risk factor for future preterm births in twin pregnancies.

Implications of idiopathic preterm delivery for previous and subsequent pregnancies

Maternal risk factors for preterm birth: a country-based population analysis

An Association of Chorionicity with Preterm Twin Birth

BackgroundWomen with systemic lupus erythematosus (SLE) are known to have more difficulty in achieving a successful pregnancy than healthy women. They have a higher risk for adverse pregnancy outcomes (APOs)...

Cerclage placement in twin pregnancies with short or dilated cervix does not prevent preterm birth: a fragility index assessment

A high rate of preterm birth has been reported in Okinawa Prefecture, the southernmost island prefecture of Japan. Hence, this study aimed to identify the risk factors for preterm birth in this prefecture. This retrospective study included data from January 2013 to December 2019 from three facilities in Okinawa Prefecture. Of 13,468 cases of preterm birth at ≥ 22 weeks of gestation, 11,868 were included in this study. Stillbirth and multiparity cases were excluded. First, we compared the overall preterm and full-term birth groups by categorizing the patient background, obstetric, and fetal risk factors. Further, we categorized preterm births into three groups (22-27, 28-33, and 34-36 weeks of gestation) and examined patient background factors to identify potential risk factors for the occurrence of preterm birth in each group. Preterm births accounted for 21.2% (2,521 cases) of all cases, with the rates of 2.6% (317 cases), 6.7% (800 cases), and 11.8% (1,404 cases) at 22-27, 28-33, and 34-36 weeks of gestation, respectively. To prevent preterm birth in Okinawa Prefecture, the present study specifically focused on patient background characteristics. In the multinomial logistic regression, the risk factors for preterm birth at 22-27 weeks of gestation were previous preterm birth (P < 0.0001) and lower age (P = 0.026); at 28-33 weeks of gestation, the risk factors were previous preterm birth (P < 0.0001) and history of cervical conization (P = 0.009); and at 34-36 weeks of gestation, only previous preterm birth (P < 0.0001) was a risk factor. Previous preterm birth, younger age, and history of cervical conization were risk factors for Preterm birth in Okinawa. To reduce premature births in Okinawa Prefecture, it is important to pick up women with these risk factors and provide them with appropriate guidance and education on an ongoing basis.

In the United States, ∼12% of all neonates are born preterm. Prior excisional procedures to diagnose and treat cervical dysplasia are a risk factor of preterm delivery. Studies on the risk for preterm birth in women after cold knife conization, laser cone, or loop electrosurgical excision procedure (LEEP) have provided conflicting results. One consideration is whether the increased risk for preterm birth is attributable to the cervical excision procedure itself or secondary to risk factors associated with cervical dysplasia. This review was performed to assess whether LEEP increases the risk for preterm birth before 37 weeks’ gestation and to clarify whether the increased risk for preterm birth is attributable to the procedure or to risk factors associated with cervical dysplasia. The review and meta-analysis were based on a predesigned protocol; PubMed, EMBASE, SCOPUS, CENTRAL, and ClinicalTrials.gov databases were searched. The review included cohort and case-control studies that compared rates of preterm birth in women with prior LEEP and women with no history of cervical excision. The primary outcome was preterm birth at less than 37 weeks. Secondary outcomes were preterm birth at less than 34 weeks, spontaneous preterm birth, preterm premature rupture of membranes, and perinatal mortality. The exposure was a history of LEEP for treatment of cervical dysplasia. Two unexposed categories included women with no or unknown history of cervical dysplasia and women with a history of cervical dysplasia but no excisional procedure. Data were analyzed using Stata 12.0 with METAN software. From 559 publications, 47 studies were examined; the final analysis included 16 retrospective cohort and 2 prospective cohort studies and 1 case-control study. These reports comprised 6589 patients with a history of LEEP (exposed) and 1,415,015 without a history of LEEP (unexposed). All studies reported preterm birth at less than 37 weeks’ gestation as an outcome. Loop electrosurgical excision procedure was associated with a higher risk for preterm birth at less than 37 weeks (8.8% vs 5.1%; pooled relative risk (RR) 1.61; 95% confidence interval [CI], 1.35–1.92; P = 0.001). No statistically significant difference was found in the risk for preterm birth when the prior LEEP group was compared with women with a history of cervical dysplasia but no excision procedure (4 studies: 10.0% vs 7.2%; pooled RR, 1.08; 95% CI, 0.88–1.33; P = 0.654). The association between LEEP and preterm birth persisted when the comparison group was women with either no history or unknown history of dysplasia (15 studies: 8.6% vs 4.6%; pooled RR, 1.86; 95% CI, 1.58–2.21; P = 0.69). In 8 studies, spontaneous preterm birth at less than 37 weeks could specifically be assessed. Although a similar magnitude of increase in risk was found, it was not statistically significant (8 studies: 6.8% vs 3.4%; pooled RR, 1.60; 95% CI, 0.99–2.55). The risk for preterm premature rupture of membranes was increased greater than 2-fold in women with a history of LEEP (6 studies: 5.1% vs 2.5%; pooled RR, 2.37; 95% CI, 1.64–3.44), as was the risk for preterm birth at less than 34 weeks (5 studies: 2.9% vs 2.3%; pooled RR, 2.21; 95% CI, 1.33–3.67). The perinatal mortality risk was elevated in women with a prior LEEP but was not statistically significant (1.0% vs0.8%; pooled RR, 1.63; 95% CI, 0.95–2.80; P = 0.911). Women with a prior LEEP are at increased risk for preterm birth before 37 weeks, but the risk was not significantly different when compared with women with prior dysplasia but no cervical excision. Risk factors of dysplasia and preterm birth are shared, and LEEP itself may not be an independent risk factor of preterm birth. If LEEP is not an independent risk factor of preterm birth, the risk and benefits of LEEP or expectant management might be altered, thus ensuring optimal therapy without fear of increasing the risk for preterm birth.

Background: Annually, an estimated 20 million (13%) low-birthweight (LBW) and 15 million (11.1%) preterm infants are born worldwide. A paucity of data and reliance on hospital-based studies from low-income countries make it difficult to quantify the true burden of LBW and PB, the leading cause of neonatal and under-five mortality. We aimed to determine the incidence and risk factors for LBW and preterm birth in Lira district of Northern Uganda. Methods: This was a community-based cohort study, nested within a cluster-randomized trial, designed to study the effect of a combined intervention on facility-based births. In total, 1877 pregnant women were recruited into the trial and followed from 28 weeks of gestation until birth. Infants of 1556 of these women had their birthweight recorded and 1279 infants were assessed for preterm birth using a maturity rating, the New Ballard Scoring system. Low birthweight was defined as birthweight <2.5kg and preterm birth was defined as birth before 37 completed weeks of gestation. The risk factors for low birthweight and preterm birth were analysed using a multivariable generalized estimation equation for the Poisson family. Results: The incidence of LBW was 121/1556 or 7.3% (95% Confidence interval (CI): 5.4–9.6%). The incidence of preterm births was 53/1279 or 5.0% (95% CI: 3.2–7.7%). Risk factors for LBW were maternal age ≥35 years (adjusted Risk Ratio or aRR: 1.9, 95% CI: 1.1–3.4), history of a small newborn (aRR: 2.1, 95% CI: 1.2–3.7), and maternal malaria in pregnancy (aRR: 1.7, 95% CI: 1.01–2.9). Intermittent preventive treatment (IPT) for malaria, on the other hand, was associated with a reduced risk of LBW (aRR: 0.6, 95% CI: 0.4–0.8). Risk factors for preterm birth were maternal HIV infection (aRR: 2.8, 95% CI: 1.1–7.3), while maternal education for ≥7 years was associated with a reduced risk of preterm birth (aRR: 0.2, 95% CI: 0.1–0.98) in post-conflict northern Uganda. Conclusions: About 7.3% LBW and 5.0% PB infants were born in the community of post-conflict northern Uganda. Maternal malaria in pregnancy, history of small newborn and age ≥35 years increased the likelihood of LBW while IPT reduced it. Maternal HIV infection was associated with an increased risk of PB compared to HIV negative status. Maternal formal education of ≥7 years was associated with a reduced risk of PB compared to those with 0–6 years. Interventions to prevent LBW and PBs should include girl child education, and promote antenatal screening, prevention and treatment of malaria and HIV infections.

To assess the association between preterm first birth and preterm second birth according to gestational age and to determine the role of placental disorder in recurrent preterm birth. Population-based registry study. Medical Birth Registry of Norway and Statistics Norway. Women (n = 213 335) who gave birth to their first and second singleton child during 1999-2014 (total n = 426 670 births). Multivariate logistic regression analyses, adjusted for placental disorders, maternal, obstetric and socio-economic factors. Extremely preterm (<28+0 weeks), very preterm (28+0 -33+6 weeks) and late preterm (34+0 -36+6 weeks) second birth. Preterm birth (<37 weeks) rates were 5.6% for first births and 3.7% for second births. Extremely preterm second births (0.2%) occurred most frequently among women with an extremely preterm first birth (aOR 12.90, 95% CI 7.47-22.29). Very preterm second births (0.7%) occurred most frequently after an extremely preterm birth (aOR 12.98, 95% CI 9.59-17.58). Late preterm second births (2.8%) occurred most frequently after a previous very preterm birth (aOR 6.86, 95% CI 6.11-7.70). Placental disorders contributed 30-40% of recurrent extremely and very preterm births and 10-20% of recurrent late preterm birth. A previous preterm first birth was a major risk factor for a preterm second birth. The contribution of placental disorders was more pronounced for recurrent extremely and very preterm birth than for recurrent late preterm birth. Among women with any category of preterm first birth, more than one in six also had a preterm second birth (17.4%). Preterm first birth is a major risk factor for subsequent preterm birth, regardless of maternal, obstetric or fetal risk factors.

Background: Twin pregnancies are associated with an increased risk of adverse maternal and neonatal outcomes, mainly owing to prematurity. Few studies have evaluated the risk factors for preterm birth (PTB) in Chinese population. The objective of this study is to present the short-term maternal-neonatal outcomes, investigating the potential risk factors associated with preterm birth in Chinese twin pregnancies.Methods: A multi-center retrospective study of women pregnant with twins ≥28 weeks of gestation was conducted. Maternal and neonatal outcomes were analyzed. Logistic regression was used to identify potential risk factors for PTB before 37, 34, and 32 weeks, respectively.Results: A total of 3,288 twin pregnancies and 6,576 neonates were included in 99,585 pregnancies. The rate of twin pregnancy was 3.3%, while the PTB rate before 37, 34, and 32 weeks among this population were 62.1, 18.8, and 10.4%, respectively. Logistic regression revealed that monochorionicity [Odds ratio (OR) 3.028, 95% confident interval (CI) 2.489–3.683, P < 0.001], gestational weight gain (GWG) <10 kg (OR 2.285, 95% CI 1.563–3.339, P < 0.001) and GWG between 10 and 15 kg (OR 1.478, 95% CI 1.188–1.839, P < 0.001), preeclampsia (PE) (OR 3.067, 95% CI 2.142–4.390, P < 0.001), and intrahepatic cholestasis of pregnancy (ICP) (OR 3.122, 95% CI 2.121–4.596, P < 0.001) were the risk factors for PTB before 37 weeks. Monochorionicity (OR 2.865, 95% CI 2.344–3.501, P < 0.001), age < 25 years (OR 1.888, 95% CI 1.307–2.728, P = 0.001), and GWG <10 kg (OR 3.100, 95% CI 2.198–4.372, P < 0.001) were risk factors for PTB before 34 weeks. Monochorionicity (OR 2.566, 95% CI 1.991–3.307, P < 0.001), age younger than 25 years (OR 1.964, 95% CI 1.265–3.048, P = 0.003), and GWG <10 kg (OR 4.319, 95% CI 2.931–6.364, P < 0.001) were the risk factors for PTB before 32 weeks.Conclusions: Monochorionicity and GWG <10 kg were two major risk factors for PTB before 32, 34, and 37 weeks, whereas maternal age, PE, and ICP were also risk factors for PTB in specific gestational age.

Objective: To evaluate for the presence of risk factors (RFs) for preterm birth (PTB) in women without prior PTB having second trimester cervical length (CL) screening, and to estimate the utility of RF screening.Methods: “Low-risk” singletons were prospectively screened with midtrimester transvaginal ultrasound CL. Prior PTB, intrauterine fetal demise and lethal anomalies were excluded. Women were analyzed based on second trimester CL (<25 mm versus ≥25 mm) and the presence of RFs for PTB. A p-value of < 0.05 was considered significant.Results: A total of 639 women were screened; 8% had CL <25 mm. Ninety-eight percent of women with CL <25 mm and 95% of women with CL ≥25 mm had RFs for PTB. Five percent of women with a CL ≥25 mm delivered preterm as compared to 18% with CL <25 mm (p < 0.01). Treatment of cervical dysplasia, drug use during the pregnancy and unmarried status were significantly more common in women with CL <25 mm than CL ≥25 mm. When data were analyzed by CL, the presence of additional RFs did not add to the prediction of PTB <37 weeks.Discussion: Over 95% of singleton gestations without prior PTB have ≥1 other RF for PTB. In women without prior PTB, assessment of other PTB RFs does not add to prediction of PTB provided by CL alone.

BackgroundThis study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).MethodsThis multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.ResultsFor the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.ConclusionCerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.