Unexplained fetal death is associated with increased concentrations of anti-angiogenic factors in amniotic fluid

Objective.?Angiogenesis is critical for successful pregnancy. An anti-angiogenic state has been implicated in preeclampsia, fetal growth restriction and fetal death. Increased maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, have been reported in women with preeclampsia and in those with fetal death. Recent observations indicate that an excess of sVEGFR-1 and soluble endoglin (sEng) is also present in the amniotic fluid of patients with preeclampsia. The aim of this study was to determine whether fetal death is associated with changes in amniotic fluid concentrations of sVEGFR-1 and sEng, two powerful anti-angiogenic factors.

Study design.?This cross-sectional study included patients with fetal death (n?=?35) and controls (n?=?129). Fetal death was subdivided according to clinical circumstances into: (1) unexplained (n?=?25); (2) preeclampsia and/or placental abruption (n?=?5); and (3) chromosomal/congenital anomalies (n?=?5). The control group consisted of patients with preterm labor (PTL) who delivered at term (n?=?92) and women at term not in labor (n?=?37). AF concentrations of sVEGFR-1 and sEng were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied.

Results.?(1) Patients with a fetal death had higher median amniotic fluid concentrations of sVEGFR-1 and sEng than women in the control group (p?<?0.001 for each); (2) these results remained significant among different subgroups of stillbirth (p?<?0.05 for each); and (3) amniotic fluid concentrations of sVEGFR-1 and those of sEng above the third quartile were associated with a significant risk of unexplained preterm fetal death (adjusted OR?=?10.8; 95%CI 1.3–89.2 and adjusted OR 87; 95% CI 2.3–3323, respectively).

Conclusion.?Patients with an unexplained fetal death at diagnosis are characterized by an increase in the amniotic fluid concentrations of sVEGFR-1 and sEng. These observations indicate that an excess of anti-angiogenic factors in the amniotic cavity is associated with unexplained fetal death especially in preterm gestations.     

Perinatal outcomes in patients with gestational diabetes mellitus by race/ethnicity

Objective.?To determine if racial/ethnic differences exist in perinatal outcomes in women with gestational diabetes mellitus (GDM).

Methods.?This is a retrospective cohort study of singleton pregnancies with GDM cared for by the Sweet Success: California Diabetes and Pregnancy Program (CDAPP) between 2001 and 2004 at inpatient obstetric and neonatal services in California. There were a total of 26,411 women with gestational diabetes who were subgrouped by four races/ethnicities: Caucasian, African-American, Latina, and Asian. The chi-squared test was used to compare the dichotomous outcomes and p?<?0.05 was used to indicate statistical significance. Multivariable logistic regression analyses were performed to control for potential confounders. Perinatal outcomes, including severity of GDM, cesarean delivery (CD), birthweight, preterm birth, intrauterine fetal demise (IUFD) and neonatal intensive care unit (NICU) admission were compared.

Results.?Compared to Caucasians, African-Americans had higher odds of primary CD [aOR?=?1.29, 95% CI (1.05–1.59)] while lower odds were seen in Latinas [aOR?=?0.84, 95% CI (0.75–0.94)] and Asians [aOR?=?0.86, 95% CI (0.77–0.96)]. Asians had lower odds [aOR?=?0.58 (95% CI 0.48–0.70)] of birthweight >4000?g. African-Americans had highest odds of IUFD [aOR?=?5.93 95% CI (1.73–20.29)]. There were no differences in NICU admission.

Conclusion.?Perinatal outcomes in women diagnosed with GDM differ by racial/ethnic group. Such variation can be used to individually counsel women with GDM.     

The use of angiogenic biomarkers in maternal blood to identify which SGA fetuses will require a preterm delivery and mothers who will develop pre-eclampsia

Objective: To determine (1) whether maternal plasma concentrations of angiogenic and anti-angiogenic factors can predict which mothers diagnosed with “suspected small for gestational age fetuses (sSGA)” will develop pre-eclampsia (PE) or require an indicated early preterm delivery (≤?34 weeks of gestation); and (2) whether risk assessment performance is improved using these proteins in addition to clinical factors and Doppler parameters.

Methods: This prospective cohort study included women with singleton pregnancies diagnosed with sSGA (estimated fetal weight <10th percentile) between 24 and 34 weeks of gestation (n?=?314). Plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), soluble endoglin (sEng) and placental growth factor (PlGF) were determined in maternal blood obtained at the time of diagnosis. Doppler velocimetry of the umbilical (Umb) and uterine (UT) arteries was performed. The outcomes were (1) subsequent development of PE; and (2) indicated preterm delivery at ≤34 weeks of gestation (excluding deliveries as a result of spontaneous preterm labor, preterm pre-labor rupture of membranes or chorioamnionitis).

Results: (1) The prevalence of PE and indicated preterm delivery was 9.2% (n?=?29/314) and 7.3% (n?=?23/314), respectively; (2) the area under the receiver operating characteristic curve (AUC) for the identification of patients who developed PE and/or required indicated preterm delivery was greater than 80% for the UT artery pulsatility index (PI) z-score and each biochemical marker (including their ratios) except sVEGFR-1 MoM; (3) using cutoffs at a false positive rate of 15%, women with abnormal plasma concentrations of angiogenic/anti-angiogenic factors were 7–13 times more likely to develop PE, and 12–22 times more likely to require preterm delivery than those with normal plasma MoM concentrations of these factors; (4) sEng, PlGF, PIGF/sEng and PIGF/sVEGFR-1 ratios MoM, each contributed significant information about the risk of PE beyond that provided by clinical factors and/or Doppler parameters: women who had low MoM values for these biomarkers were at 5–9 times greater risk of developing PE than women who had normal values, adjusting for clinical factors and Doppler parameters (adjusted odds ratio for PlGF: 9.1, PlGF/sEng: 5.6); (5) the concentrations of sVEGFR-1 and PlGF/sVEGFR-1 ratio MoM, each contributed significant information about the risk of indicated preterm delivery beyond that provided by clinical factors and/or Doppler parameters: women who had abnormal values were at 8–9 times greater risk for indicated preterm delivery, adjusting for clinical factors and Doppler parameters; and (6) for a two-stage risk assessment (Umb artery Doppler followed by Ut artery Doppler plus biochemical markers), among women who had normal Umb artery Doppler velocimetry (n?=?279), 21 (7.5%) developed PE and 11 (52%) of these women were identified by an abnormal UT artery Doppler mean PI z-score (>2SD): a combination of PlGF/sEng ratio MoM concentration and abnormal UT artery Doppler velocimetry increased the sensitivity of abnormal UT artery Doppler velocimetry to 76% (16/21) at a fixed false-positive rate of 10% (p?=?0.06).

Conclusion: Angiogenic and anti-angiogenic factors measured in maternal blood between 24 and 34 weeks of gestation can identify the majority of mothers diagnosed with “suspected SGA” who subsequently developed PE or those who later required preterm delivery ≤34 weeks of gestation. Moreover, incorporation of these biochemical markers significantly improves risk assessment performance for these outcomes beyond that of clinical factors and uterine and umbilical artery Doppler velocimetry.     

Nulliparity and preterm birth in the era of obesity epidemic

Objective.?To assess the impact of obesity on preterm birth among nulliparous women.

Methods.?Retrospective cohort study of nulliparous mothers delivering infants in Florida between 2004 and 2007. Women were classified as non-obese (pre-pregnancy body mass index (BMI) <30) or obese (BMI?≥?30). The main outcomes assessed were preterm birth, very preterm birth and extremely preterm birth. Risk estimates were obtained using logistic regression. Multiparous non-obese mothers were the referent group for all analyses.

Results.?As compared to multiparous women, nulliparous mothers had an increased risk of very preterm and extremely preterm birth with the highest risk observed for extremely preterm birth (odds ratios (OR)?=?1.37, 95% CI?=?1.28, 1.47) (p for trend <0.01). Obese nulliparous mothers had an elevated risk of preterm, very preterm and extremely preterm birth, with the risk of extremely preterm birth being the most pronounced (OR?=?1.97, 95% CI?=?1.75–2.22) [p for trend <0.05]. The heightened risk associated with obesity among nulliparous women was observed across all racial/ethnic sub-populations, with black nulliparous obese mothers being at greatest risk of all preterm birth-subtypes.

Conclusions.?Obesity is a risk marker for preterm, very preterm and extremely preterm birth among first-time mothers and particularly among blacks and Hispanics.     

The impact of fetal gender on preterm birth in a southern Chinese population

Objective: This study was conducted to determine whether carrying a singleton male fetus increases the risk of preterm birth (PTB) in Chinese women. Methods: A retrospective cohort study was conducted on women with singleton pregnancies and delivered in our hospital. Maternal characteristics, pregnancy outcome, and incidence of PTB, were compared between women carrying a male versus a female fetus. The independent effect of a male fetus on PTB was examined with multiple logistic regression analysis adjusting for the other confounding factors identified. Results: There were significant differences in maternal and infant characteristics between women with a male versus a female fetus. Despite similar or lower incidences of complications and labor induction, women with a male fetus had increased birth <37 weeks (7.0% versus 6.2%, p?<?0.001) and birth at 34–36 weeks (5.15% versus 4.4%, p?<?0.001), but not for birth <34 weeks (2.0% versus 1.8%, p?=?0.163). Regression analysis confirmed the association between male fetus with birth at 34–36 weeks (aOR 1.11, 95% CI 1.10–1.33) and spontaneous preterm labor (aOR 1.09, 95% CI 1.00–1.19). Conclusions: The results confirmed that carrying a male fetus is an independent risk factor for spontaneous preterm labor and PTB at 34–36 weeks gestation in southern Chinese women.     

The risk of preterm birth associated with a low cerebroplacental ratio

Objective: This paper investigated whether a cerebroplacental ratio (CPR)?Methods: This was a retrospective cohort study of 8977 women during 2014 and 2015 at a major tertiary referral hospital. Selection criteria included women who had a nonanomalous, singleton fetus and underwent an ultrasound scan between 23?+?0–36?+?6 weeks gestation.

Results: A low CPR increased the risk of preterm birth or birth within 2 weeks of the scan with the highest odds of birth within 2 weeks seen at 28-week gestation (odds ratio (OR) 3.78, 95%CI 1.63–8.77) – the mode of delivery was most likely emergency caesarean section for nonreassuring fetal status (aOR 2.11, 95%CI 1.69–2.64, p?p?Conclusions: A low CPR is associated with an increased risk of preterm birth and birth within 2 weeks but not spontaneous preterm birth.     

Endocan,a putative endothelial cell marker,is elevated in preeclampsia,decreased in acute pyelonephritis,and unchanged in other obstetrical syndromes

Objective: Endocan, a dermatan sulphate proteoglycan produced by endothelial cells, is considered a biomarker for endothelial cell activation/dysfunction. Preeclampsia is characterized by systemic vascular inflammation, and endothelial cell activation/dysfunction. Therefore, the objectives of this study were to determine whether: (1) plasma endocan concentrations in preeclampsia differ from those in uncomplicated pregnancies; (2) changes in plasma endocan concentration relate to the severity of preeclampsia, and whether these changes are specific or observed in other obstetrical syndromes such as small-for-gestational age (SGA), fetal death (FD), preterm labor (PTL) or preterm prelabor rupture of membranes (PROM); (3) a correlation exists between plasma concentration of endocan and angiogenic (placental growth factor or PlGF)/anti-angiogenic factors (soluble vascular endothelial growth factor receptor or sVEGFR-1, and soluble endoglin or sEng) among pregnancies complicated by preeclampsia; and (4) plasma endocan concentrations in patients with preeclampsia and acute pyelonephritis (both conditions in which there is endothelial cell activation) differ.

Method: This cross-sectional study included the following groups: (1) uncomplicated pregnancy (n?=?130); (2) preeclampsia (n?=?102); (3) pregnant women without preeclampsia who delivered an SGA neonate (n?=?51); (4) FD (n?=?49); (5) acute pyelonephritis (AP; n?=?35); (6) spontaneous PTL (n?=?75); and (7) preterm PROM (n?=?64). Plasma endocan concentrations were determined in all groups, and PIGF, sEng and VEGFR-1 plasma concentrations were measured by ELISA in the preeclampsia group.

Results: (1) Women with preeclampsia had a significantly higher median plasma endocan concentration than those with uncomplicated pregnancies (p?=?0.004); (2) among women with preeclampsia, the median plasma endocan concentration did not differ significantly according to disease severity (p?=?0.1), abnormal uterine artery Doppler velocimetry (p?=?0.7) or whether diagnosis was made before or after 34 weeks gestational age (p?=?0.3); (3) plasma endocan concentration in women with preeclampsia correlated positively with plasma anti-angiogenic factor concentrations [sVEGFR-1: Spearman rho 0.34, p?=?0.001 and sEng: Spearman rho 0.30, p?=?0.003]; (4) pregnancies complicated by acute pyelonephritis with bacteremia had a lower median plasma endocan concentration than pregnancies complicated by acute pyelonephritis without bacteremia (p?=?0.004), as well as uncomplicated pregnancies (p?=?0.001); and (5) there was no significant difference in the median plasma endocan concentration between uncomplicated pregnancies and those complicated by FD, delivery of an SGA neonate, PTL or preterm PROM (other members of the “great obstetrical syndromes”; each p?>?0.05).

Conclusion: Median maternal plasma endocan concentrations were higher preeclampsia and lower in acute pyelonephritis with bacteremia than in uncomplicated pregnancy. No significant difference was observed in the median plasma endocan concentration between other great obstetrical syndromes and uncomplicated pregnancies. The difference in the direction of change of endocan in preeclampsia and acute pyelonephritis with bacteremia may be consistent with the view that both disease entities differ in pathogenic mechanisms, despite their associations with systemic vascular inflammation and endothelial cell activation/dysfunction.     

Late-onset preeclampsia is associated with an imbalance of angiogenic and anti-angiogenic factors in patients with and without placental lesions consistent with maternal underperfusion

Objective: An imbalance between maternal angiogenic/anti-angiogenic factors concentrations has been observed in preeclampsia (PE) and other obstetrical syndromes. However, the frequency of pathologic findings in the placenta and the changes in maternal plasma angiogenic/anti-angiogenic factor concentrations differ between late- and early-onset PE. The aim of this study was to determine if the maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 and 2 (sVEGFR-1 and sVEGFR-2) are different in late-onset PE with and without placental pathologic findings consistent with maternal underperfusion. Study design: A cross-sectional study was conducted including 64 uncomplicated women and 66 women with late-onset PE (>34 weeks) who had blood samples and placenta available for pathologic examination. Patients with late-onset PE were divided into those with and without placental histologic findings consistent with maternal underperfusion as proposed by the Society for Pediatric Pathology. Maternal plasma concentrations of PlGF, sEng, sVEGFR-1 and sVEGRF-2 were determined by ELISA. Non-parametric statistics were used for analysis. Results: 1) the prevalence of placental histological findings consistent with maternal underperfusion among women with late-onset PE was higher than that of those with an uncomplicated pregnancy (47% (31/66) vs. 7.8% (5/64), respectively; p?<?0.01); 2) patients with late-onset PE and histological findings consistent with maternal underperfusion had a significantly lower median plasma concentration of PlGF, plasma PlGF/sVEGFR-1 ratio and plasma PlGF/sEng ratio than those with late-onset PE without placental underperfusion lesions (each p?<?0.05); 3) the most common pathological findings in the placenta of patient with PE were lesions consistent with villous changes (77%, 24/31); and 4) isolated vascular lesions in the placenta were found only in 2 cases (6.5%), and the rest had a combination of villous and vascular lesions. Conclusions: Nearly half of the patients with late-onset PE have placental lesions consistent with maternal underperfusion. These lesions are associated with an imbalance in the maternal concentration of angiogenic/anti-angiogenic factors. We propose that there is a link between maternal underperfusion and an anti-angiogenic state characterized by the changes in the concentrations of angiogenic and anti-angiogenic factors in women with late onset PE.     

The effect of prepregnancy body mass index on birth weight,preterm birth,cesarean section,and preeclampsia in pregnant women

Objective: The objective of this study is to determine the impact of maternal prepregnancy BMI on birth weight, preterm birth, cesarean section, and preeclampsia among pregnant women delivering singleton life birth.

Methods: A cross-sectional study of 4397 women who gave singleton birth in Tehran, Iran from 6 to 21 July 2015, was conducted. Women were categorized into four groups: underweight (BMI?2), normal (BMI 18.5–25?kg/m²), overweight (BMI 25–30?kg/m²) and obese (BMI >30?kg/m²), and their obstetric and infant outcomes were analyzed using both univariate and multivariate logistic regression.

Results: Prepregnancy BMI of women classified 198 women as underweight (4.5%), 2293 normal (52.1%), 1434 overweight (32.6%), and 472 as obese (10.7%). In comparison with women of normal weight, women who were overweight or obese were at increased risk of preeclampsia (odds ratio (OR)?=?1.47, 95% CI?=?1.06–2.02; OR?=?3.67, 95% CI?=?2.57–5.24, respectively) and cesarean section (OR?=?1.21, 95% CI?=?1.04–1.41; OR?=?1.35, 95% CI?=?1.06–1.72, respectively). Infants of obese women were more likely to be macrosomic (OR?=?2.43, 95% CI?=?1.55–3.82).

Conclusion: Prepregnancy obesity is a risk factor for macrosomia, preeclampsia, and cesarean section and need for resuscitation.     

Fish oil supplementation improves pregnancy outcomes and size of the newborn: a meta-analysis of 21 randomized controlled trials

Objective: To observe the effects of fish oil on related pregnancy outcomes.

Methods: A systematic search of the Medline, EMBASE and Cochrane’s library databases was conducted for the randomized controlled trials published till February 2015 that compared the effects of fish oil supplementation with a control diet in women during pregnancy.

Results: Twenty-one studies comprising 10?802 pregnant women were included. Dietary fish oil was associated with a 5.8-day increase in gestational age of the newborn, a 22% reduced risk for early preterm delivery (risk ratio [RR]?=?0.78, 95% CI: 0.64–0.95, p?=?0.01) and a 10% reduction in preterm delivery (RR?=?0.90, 95% CI 0.81–1.00, p?=?0.05). Fish oil supplementation was associated with higher infantile birth weight (51.23?g), birth length (0.28?cm) and head circumference (0.09?cm), and a 23% lower risk of low birth weight. No benefit from fish oil supplementation was found with regard to risk of intrauterine growth restriction or stillbirth.

Conclusions: Dietary fish oil during pregnancy was associated with reduced risk of preterm delivery and improved size of the newborn. Fish oil during pregnancy may be an effective prophylactic for preterm delivery.     

Biomarkers of inflammation and placental dysfunction are associated with subsequent preterm birth

Objective.?To assess whether the analysis of high sensitivity C-Reactive Protein (hsCRP), a biomarker of inflammation, and placental growth factor (PlGF), a biomarker of placental dysfunction, could help identify patients at risk for preterm birth (PTB).

Methods.?We performed a prospective cohort study of women with symptoms of preterm labor (22–33 6/7 weeks). Maternal serum was analyzed for hsCRP and PlGF. Median biomarker values were used as analytic cut-points. We performed chi-square tests of association between biomarkers and PTB, nonparametric tests to compare medians, and logistic regression to determine the odds of PTB associated with biomarker values. Test characteristics of each biomarker were calculated.

Results.?56.3% of the cohort (N = 96) delivered preterm. Median hsCRP (N = 78) was 4.34 mg/L, and median PlGF (N = 86) was 558.25 mg/l. In the setting of inflammation (high hsCRP), women with low PlGF had a 6.84-fold (95%CI: 1.57–29.80) increased risk of PTB. In the setting of placental dysfunction (low PlGF), women with high hsCRP had a 5.97-fold (95%CI: 1.52–23.43) increased risk of PTB.

Conclusions.?Our results suggest an interplay between inflammation and placental dysfunction in the pathogenesis of PTB. Analyzing biomarkers that reflect different pathways of PTB may hold promise for identifying patients at greatest risk.     

What factors are related to recurrent preterm birth among underweight women?*

Objective: Our objective was to identify factors associated with recurrent preterm birth among underweight women.

Methods: Maternally linked hospital and birth certificate records of deliveries in California between 2007 and 2010 were used. Consecutive singleton pregnancies of women with underweight body mass index (BMI?<18.5?kg/m²) in the first pregnancy were analyzed. Pregnancies were categorized based on outcome of the first and second birth as: term-term; term-preterm; preterm-term and preterm-preterm.

Results: We analyzed 4971 women with underweight BMI in the first pregnancy. Of these, 670 had at least one preterm birth. Among these 670, 86 (21.8%) women experienced a recurrent preterm birth. Odds for first term – second preterm birth were decreased for increases in maternal age (aOR: 0.90, 95%CI: 0.95–0.99) whereas inter-pregnancy interval <6?months was related to both first term – second preterm birth (aOR:1.66, 95%CI: 1.21–2.28) and first preterm birth – second term birth (aOR: 1.43, 95%CI: 1.04–1.96). Factors associated with recurrent preterm birth were: negative or no change in pre-pregnancy weight between pregnancies (aOR: 1.67, 95%CI: 1.07–2.60), inter-pregnancy interval?<6?months (aOR: 2.14, 95%CI: 1.29–3.56), and maternal age in the first pregnancy (aOR: 0.93, 95%CI: 0.90–0.97).

Conclusions: Recurrent preterm birth among underweight women was associated with younger age, short inter-pregnancy interval, and negative or no weight change between pregnancies.     

Has improved health care provision impacted on the obstetric outcome in teenage women?

Objective: To determine the obstetric outcome in teenage women managed in the recent decade with easily accessible health care provision. Methods: In a retrospective cohort study, maternal demographics, underlying medical conditions, obstetric complications, preterm birth, type of labor, mode of delivery, and perinatal mortality were compared between 1505 women aged ≤19 years (study group) with 10,320 women aged 20–24 years (comparison group), who were carrying singleton pregnancies beyond 24 weeks of gestation and managed in our hospital between January 1998 and June 2008. Results: The study and comparison groups accounted for 2.2% and 15.1% respectively of the total deliveries. Despite comparable health status and rates of other obstetric complications, teenage women was associated with birth <34 weeks (aOR 2.45, 95% CI 1.67–3.60), birth at 34–36 weeks (aOR 2.13, 95% CI 1.71–2.65), and reduced instrumental vaginal (aOR 0.62, 95% CI 0.50–0.77) and caesarean (aOR 0.79, 95% CI 0.64–0.97) delivery, without increase in perinatal mortality. Conclusions: Teenage women had increased preterm birth, despite improved health care provision, nutrition, and similar incidence of other obstetric complications, but the obstetric and perinatal outcome remained favorable.     

Serum and plasma determination of angiogenic and anti-angiogenic factors yield different results: The need for standardization in clinical practice

Objective.?The importance of an anti-angiogenic state as a mechanism of disease in preeclampsia is now recognized. Assays for the determination of concentrations of soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF) and soluble endoglin (sEng) have been developed for research and clinical laboratories. A key question is whether these factors should be measured in plasma or serum. The purpose of this study was to determine if there are differences in the concentrations of these analytes between plasma and serum in normal pregnancy and in preeclampsia.

Methods.?Samples of maternal blood were obtained by venipuncture and collected in EDTA (lavender top) and serum collection tubes (red top). A standard laboratory procedure was implemented for the centrifugation, aliquoting and storage of samples. Plasma and serum from 70 women with normal pregnancies and 34 patients with preeclampsia were assayed for sVEGFR-1, sVEGFR-2, PlGF and sEng by ELISA. Nonparametric paired tests were used for analyses.

Results.?A significant difference between plasma and serum concentration was observed for sVEGFR-1 and sVEGFR-2 in normal pregnancy, and for sVEGFR-1, sVEGFR-2, PlGF and sEng in women with preeclampsia.

Conclusion.?The concentrations of sVEGFR-1, sVEGFR-2, PlGF and sEng when measured in maternal plasma and in serum are different. Therefore, the matrix used for the assay (serum versus plasma) needs to be considered when selecting thresholds for predictive studies and interpreting the growing body of literature on this subject.     

Maternal hepatitis B surface antigen carrier status and its impact on neonatal outcomes: a cohort study of 21 947 singleton newborns in China

Objective: To explore the impact of maternal hepatitis B surface antigen (HBsAg) carrier status on neonatal outcomes.

Methods: A retrospective cohort study was conducted using data from medical records database of six hospitals in China. Information on maternal characteristics and selected neonatal outcomes was retrieved for all women who delivered singleton infants between 1 January 2009 and 31 December 2010.

Results: A total of 21 947 singleton newborns and their mothers were included. The prevalence of maternal HBsAg positivity was 4.2% (95% confidence interval (CI) 3.9–4.5%). Compared with infants born to HBsAg-negative women, infants born to HBsAg-positive mothers were more than twice more likely to have a malformation before (adjusted odds ratio (aOR) 2.23, 95% CI 1.15–4.30) and at birth (aOR 2.66, 95% CI 1.38–5.14), but were less likely to be macrosomia (aOR 0.67, 95% CI 0.47–0.96). No statistically significant association was found between maternal HBsAg positivity and preterm birth (aOR 1.20, 95% CI 0.95–1.51), low birth weight (aOR 1.24, 95% CI 0.91–1.69), and Apgar scores at 1?min (aOR 0.88, 95% CI 0.49–1.57) and 5?min (aOR 1.84, 95% CI 0.89–3.81).

Conclusion: Maternal HBsAg positivity may be associated with a higher risk of congenital malformation.     

Maternal asthma: pregnancy course and outcome

Objective: To evaluate the association between maternal asthma and perinatal outcome.

Study design: In this retrospective population-based cohort study, all pregnancies between 1991 and 2014 in a tertiary medical center, were included. Multiple pregnancies and congenital malformations were excluded. Pregnancy course and outcomes were compared between women with and without asthma, and multivariable generalized estimating equations were used to control for confounders.

Results: During the study period, 243,363 deliveries met the inclusion criteria, 1.35% of which (n?=?3283) occurred in women diagnosed with asthma. Multiple perinatal complications were found to be associated with maternal asthma, including hypertensive disorders, preterm delivery, and cesarean delivery. However, no significant differences between the groups were noted in neonatal outcomes, including perinatal mortality rates and low Apgar scores. In the regression model, maternal asthma was noted as an independent risk factor for preterm delivery, hypertensive disorders of pregnancy, and cesarean delivery (aOR?=?1.21, 95%CI 1.1–1.4, p?=?.007; aOR?=?1.35, 95%CI 1.2–1.6, p?p?Conclusions: Maternal asthma is associated with an increased risk for adverse pregnancy outcome. This association remains significant while controlling for variables considered to coexist with maternal asthma. Nevertheless, perinatal outcome is generally favorable.     

Temporal trends in cardiomyopathy in pregnancy and association with feto-infant morbidity outcomes

Objective: To examine temporal trends of cardiomyopathy in pregnancy and its association with feto-infant morbidity outcomes. Design and methods: We performed a population-based retrospective cohort analysis utilizing the Florida hospital discharge data linked to vital statistics for 1998 to 2007 (N?=?1 738 860). Prevalence rates and trend statistics of cardiomyopathy were computed. Conditional logistic regression models were used to generate adjusted odds ratios (AOR) and 95% confidence intervals (CI). Results: The annual prevalence of cardiomyopathy in pregnancy increased from 8.5/100 000 births to 32.7/100 000 (p for trend <0.0001), representing an absolute increase of 24% and a relative increase of 300% over the decade. Infants born to women with cardiomyopathy were at higher risk for feto-infant morbidities, including low birth weight (AOR?=?3.49, 95% CI: 2.97–4.11), very low birth weight (AOR?=?4.43, 95% CI: 2.98–6.60), preterm birth (AOR?=?3.33, 95% CI: 2.88–3.85), very preterm birth (AOR?=?5.22, 95% CI: 3.92–6.97) and small for gestational age (AOR?=?1.57, 95% CI: 1.26–1.96). Conclusion: The observed increasing prevalence of cardiomyopathy during pregnancy over the decade is of concern, as it is related to elevated risk for feto-infant morbidities. There is a need to delineate risk factors for this condition and to formulate appropriate preconception counseling for women with elevated risk for this diagnosis.     

Primiparity: An ‘intermediate’ risk group for spontaneous and medically indicated preterm birth

Objective.?Most women in their first pregnancy are at ‘unknown’ risk for preterm birth. We hypothesized that such women may be at an increased risk for preterm birth in comparison to those with a prior term birth.

Methods.?We used Missouri's maternally-linked data (1989–97), comprised of women delivering their first singleton live birth (N = 259 431) and women delivering their first two consecutive singleton live births (N = 154 810). We compared preterm birth (<37 weeks) rates among women with a previous term birth, women with no reproductive history (primiparous women), and in those with a previous preterm birth. Risks of spontaneous and medically indicated preterm birth were also examined after adjustments for confounders through multivariate log-binomial regression models.

Results.?Preterm birth rates were 8.1%, 9.6%, and 23.3% among women with a previous term birth, among primiparous women, and among those with a previous preterm birth, respectively. In comparison to women with a prior term birth, risks of spontaneous preterm birth among primiparous women and among women with a prior preterm birth were 1.1-fold (95% confidence interval (CI) 1.0, 1.2) and 2.5-fold (95% CI 2.4, 2.6) higher, respectively. These risks were higher for medically indicated preterm birth among both primiparous women (RR 1.3, 95% CI 1.2, 1.4) and those with a prior preterm birth (RR 3.2, 95% CI 3.0, 3.5) than for spontaneous preterm births.

Conclusions.?Primiparous women are at increased risk of both medically indicated and spontaneous preterm birth. The findings suggest that studies on preterm birth should consider a risk assignment to include three groups: low-risk (prior term birth), intermediate risk (primiparity), and high-risk (prior preterm birth). This strategy will be informative for the identification of women with impending risk of delivering preterm, and complications associated with prematurity.     

Polymorphisms in the vascular endothelial growth factor gene associated with recurrent spontaneous miscarriage

Abstract

Objective: To evaluate the association between the vascular endothelial growth factor (VEGF) polymorphism and the risk of recurrent spontaneous miscarriage (RSM).

Methods: The participants enrolled included 227 RSM patients and 232 women with normal fertility. We examined the potential association between RSM and 13 single nucleotide polymorphisms (rs699947, rs1570360, rs2010963, rs833068, rs833069, rs3024997, rs3024998, rs3025000, rs3025006, rs3025010, rs3025020, rs3025030 and rs3025039) of VEGF gene using the MassARRAY system.

Results: The results showed that rs3025020 located at intron 6 of VEGF gene was significantly associated with RSM (χ^2?=?12.6385, p?=?0.0004, odds ratio (OR)?=?1.6109, 95% confidence interval (CI)?=?1.2377–2.0967). Another significant association was observed for rs3025039 located in the 3′-untranslated region of VEGF gene (χ^2?=?9.7256, p?=?0.0018, OR?=?1.6492, 95% CI?=?1.2023–2.2622). Furthermore, strong linkage disequilibrium was observed in three blocks (D′?>?0.9), and significantly more T–G–C haplotypes (p?=?0.0286) and fewer C–G–C haplotypes (p?=?0.0006 after Bonferroni correction) residing in block 3 were found in RSM patients.

Conclusion: These findings point to a role for VEGF gene polymorphisms in RSM, and may be informative for future genetic or neurobiological studies on RSM.     

Early prediction of spontaneous twin very preterm birth: a population based study 2002–2012

Objective: The aim of this study was to establish early pregnancy risk indicators for spontaneous twin very preterm birth.

Methods: We conducted a retrospective observational population-based study. Twenty-one potential early pregnancy risk factors were analyzed using multivariable logistic regression to determine which of them was independently associated with spontaneous twin very preterm birth.

Results: Of 1815 spontaneous twin births 15.3% (277) occurred before 32 weeks. Previous preterm delivery (aOR 3.73; 95% CI, 2.52–5.52), nulliparity (aOR 2.94; 95% CI, 2.09–4.14), body mass index <18.5 (aOR 1.86; 95% CI, 1.12–3.10), body mass index ≥30 (aOR 1.87; 95% CI, 1.21–2.89), hysteroscopic metroplasty (aOR 1.63; 1.07–2.49), conization (aOR 2.05; 95% CI, 1.07–3.94) and monochorionicity (aOR 1.83; 95% CI, 1.28–2.63) were significantly associated with twin very preterm birth.

Conclusions: Pending verification in other populations, twin pregnancies at significant risk for spontaneous very preterm birth can be identified in early pregnancy using several risk indicators.