Linkage between In Utero Environmental Changes and Preterm Birth

ABSTRACT Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS), or Streptococcus agalactiae . However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth. IMPORTANCE GBS are a family of bacteria that frequently colonize the vagina of pregnant women. In some cases, GBS ascend from the vagina into the uterine space, leading to fetal injury and preterm birth. Unfortunately, little is known about the mechanisms underlying ascending GBS infection. In this study, we show that a GBS virulence factor, HylB, shows higher activity in strains isolated from cases of preterm birth than those isolates from rectovaginal swabs of healthy women. We discovered that GBS rely on HylB to avoid immune detection in uterine tissue, but not placental tissue, which leads to increased rates of fetal injury and preterm birth. These studies provide novel insight into the underlying mechanisms of ascending infection.

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Maternal Low Fasting Plasm Glucose in the Second Trimester is Associated with Neonatal Asphyxia

10.21203/rs.3.rs-88563/v1 ◽

2020 ◽

Author(s):

Yuan Shasha ◽

An Yaxin ◽

Yang Yuxian ◽

Li Kun ◽

Ke Jing ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Preterm Birth ◽

Apgar Score ◽

Neonatal Death ◽

Gestational Hypertension ◽

Fetal Distress ◽

In Utero ◽

Second Trimester ◽

Multivariate Logistic Regression

Abstract Background Neonatal asphyxia (NA) is associated with neonatal respiratory distress syndrome, cerebral palsy and neonatal death. Risk factors for NA have been identified as maternal hypertension, premature birth and anemia. While the effect of maternal fasting plasm glucose (FPG) in the second trimester of pregnancy on NA remains unclear. Method Retrospective data from 9661 singleton newborns and mothers were analyzed from January 2016 to July 2018 in Tongzhou district, Beijing. Multivariate logistic regression was used to investigate the risk factors of NA, adjusted for gestational hypertension, triglyceride in the second trimester of pregnancy, fetal distress in utero and preterm birth. Results Of the 9,661 newborns, 26 (2.7‰) were diagnosed with neonatal death (Apgar score 1min = 0) and 52 (5.4‰) with varying degrees of asphyxia (Apgar score 1min = 1 to 6). The asphyxia group showed lower FPG [asphyxia group vs non-asphyxia group, 4.5±0.4 vs 4.8±0.5 mmol/L, P<.01], higher triglyceride level (asphyxia group vs non-asphyxia group, 3.0±1.3 vs 2.5±1.9 mmol/L P<.01) in the second trimester, higher rates of gestational hypertension, fetal distress in utero, preterm birth than the non-asphyxia group (P<.05). Multivariate logistic regression revealed that lower FPG in the second trimester was an independent risk factor of NA [adjusted odds ratio (AOR) 0.26; 95% CI 0.08 to 0.80]. Conclusion Pregnant women with low fasting glucose in the second trimester of pregnancy are at increased risk of birth asphyxia in their offspring.

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Risk Factors for Very Preterm Births in French Guiana: The Burden of Induced Preterm Birth

American Journal of Perinatology Reports ◽

10.1055/s-0039-1678716 ◽

2019 ◽

Vol 09 (01) ◽

pp. e44-e53

Author(s):

Malika Leneuve-Dorilas ◽

Anne Favre ◽

Alphonse Louis ◽

Stéphanie Bernard ◽

Gabriel Carles ◽

...

Keyword(s):

Preterm Birth ◽

Preterm Delivery ◽

French Guiana ◽

Conditional Logistic Regression ◽

Preterm Births ◽

Public Health Problem ◽

In Utero ◽

Major Public Health Problem ◽

Multiple Pregnancies ◽

Vaginal Infections

Background Early preterm births are still represented as a major public health problem in French Guiana. The objective of the present study was to study factors associated with early preterm birth in French Guiana. Methods A monocentric age-matched case control study was conducted at the sole level 3 maternity in French Guiana. In utero fetal deaths and multiple pregnancies were not included. Cases were defined as giving birth prematurely between 22 and 32 weeks of pregnancy. Controls were defined as women delivering on term. For each case three controls were matched on age. In utero deaths, medical pregnancy interruptions and multiple pregnancies (a known major cause of preterm delivery) were excluded from the study. Sociodemographic variables, medical and obstetrical history, the complications of the current pregnancy, and the results of the last vaginal swab before delivery were recorded in the second or the third trimester. Thematic conditional logistic regression models were computed. Results Overall 94 cases and 282 matched controls were included. Preterm delivery was spontaneous in 47.9% (45/94) of the cases and induced in 52.1% (49/94).A history of preterm birth was associated with both spontaneous and induced preterm delivery. The absence of health insurance was associated with spontaneous early preterm delivery AOR (adjusted odd ratio) = 9.1 (2.2–38.3), p = 0.002 but not induced preterm delivery adjusted odd ratio (AOR) = 2.1 (0.6–6.7), p = 0.2. Gravidic hypertension, placenta praevia, intrauterine growth retardation and mostly preeclampsia (66%, 32/49) were linked to induced preterm delivery but not spontaneous delivery. Gardnerellavaginalis and group B Streptococcus infections were significantly associated with induced early preterm delivery but not spontaneous early preterm delivery. Conclusions Social factors were associated with spontaneous early preterm delivery, suggesting that efforts to reduce psychosocial stressors could lead to potential improvements. Vaginal infections were also associated with induced preterm labor suggesting that early diagnosis and treatment could reduce induced early preterm delivery. Preeclampsia was a major contributor to induced early preterm delivery. Reliable routine predictors of preeclampsia are still not available which makes its prevention impossible in first pregnancies.

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Is there a Link between Preterm Birth and In Utero Exposure to Climate Change?

Annals of Nursing Research & Practice ◽

10.26420/annnursrespract.2021.1041 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Panait ED ◽

◽

Balaceanu-Stolnici C ◽

Glavce CS ◽

Moga MA ◽

...

Keyword(s):

Preterm Birth ◽

Premature Birth ◽

Birth Rate ◽

In Utero ◽

Pediatric Care ◽

Obstetrics And Gynecology ◽

In Utero Exposure ◽

Premature Births ◽

Climate Conditions ◽

Clinical Hospital

Aim: The aim of this study is to clarify if there is a link between preterm birth and temperature as a climate factor. Our study comes after a long period of clinical experience that rose the suspicion of a possible correlation between temperature variation and peaks of premature births. Materials and method: We conducted a retrospective study on the number of births registered at the “Dr. I.A. Sbarcea” Clinical Hospital of Obstetrics and Gynecology in Brasov in 2018 and 2019. Data related to premature birth was further correlated to climate information regarding Brasov area obtained from the National Administration of Meteorology, Romania and to results of fertility statistics made publicly available by the Romanian National Institute of Statistics. Results: Our study group included 99 premature births registered at “Dr. I.A. Sbarcea” Clinical Hospital of Obstetrics and Gynecology in Brasov in 2018 and 127 in 2019. The premature birth rate peaks in August for both years of study: 2018 and 2019. Statistical data processing shows there is significant correlation between in utero exposure to extreme temperatures and registration of peaks of premature births. Conclusion: Recognizing a pattern of the raise in the premature birth rate may help the healthcare system to cope with the increased demands of the pediatric care units in time periods marked by specific climate context. Easy recognition of climate conditions that can consequently lead to a peak in the rate of premature birth can be useful for medical staff and patients.

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Evaluating the use of the QUiPP app and its impact on the management of threatened preterm labour: A cluster randomised trial

PLoS Medicine ◽

10.1371/journal.pmed.1003689 ◽

2021 ◽

Vol 18 (7) ◽

pp. e1003689

Author(s):

Helena A. Watson ◽

Naomi Carlisle ◽

Paul T. Seed ◽

Jenny Carter ◽

Katy Kuhrt ◽

...

Keyword(s):

Preterm Birth ◽

Clinical Decision Making ◽

Preterm Labour ◽

External Validation ◽

Randomised Trial ◽

In Utero ◽

Receiver Operating Curve ◽

Cluster Randomised Trial ◽

Cluster Randomised ◽

National Guidance

Background Preterm delivery (before 37 weeks of gestation) is the single most important contributor to neonatal death and morbidity, with lifelong repercussions. However, the majority of women who present with preterm labour (PTL) symptoms do not deliver imminently. Accurate prediction of PTL is needed in order ensure correct management of those most at risk of preterm birth (PTB) and to prevent the maternal and fetal risks incurred by unnecessary interventions given to the majority. The QUantitative Innovation in Predicting Preterm birth (QUIPP) app aims to support clinical decision-making about women in threatened preterm labour (TPTL) by combining quantitative fetal fibronectin (qfFN) values, cervical length (CL), and significant PTB risk factors to create an individualised percentage risk of delivery. Methods and findings EQUIPTT was a multi-centre cluster randomised controlled trial (RCT) involving 13 maternity units in South and Eastern England (United Kingdom) between March 2018 and February 2019. Pregnant women (n = 1,872) between 23+0 and 34+6 weeks’ gestation with symptoms of PTL in the analysis period were assigned to either the intervention (762) or control (1,111). The mean age of the study population was 30.2 (+/− SD 5.93). A total of 56.0% were white, 19.6% were black, 14.2% were Asian, and 10.2% were of other ethnicities. The intervention was the use of the QUiPP app with admission, antenatal corticosteroids (ACSs), and transfer advised for women with a QUiPP risk of delivery >5% within 7 days. Control sites continued with their conventional management of TPTL. Unnecessary management for TPTL was a composite primary outcome defined by the sum of unnecessary admission decisions (admitted and delivery interval >7 days or not admitted and delivery interval ≤7 days) and the number of unnecessary in utero transfer (IUT) decisions/actions (IUT that occurred or were attempted >7 days prior to delivery) and ex utero transfers (EUTs) that should have been in utero (attempted and not attempted). Unnecessary management of TPTL was 11.3% (84/741) at the intervention sites versus 11.5% (126/1094) at control sites (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.66–1.42, p = 0.883). Control sites frequently used qfFN and did not follow UK national guidance, which recommends routine treatment below 30 weeks without testing. Unnecessary management largely consisted of unnecessary admissions which were similar at intervention and control sites (10.7% versus 10.8% of all visits). In terms of adverse outcomes for women in TPTL <36 weeks, 4 women from the intervention sites and 12 from the control sites did not receive recommended management. If the QUiPP percentage risk was used as per protocol, unnecessary management would have been 7.4% (43/578) versus 9.9% (134/1,351) (OR 0.72, 95% CI 0.45–1.16). Our external validation of the QUiPP app confirmed that it was highly predictive of delivery in 7 days; receiver operating curve area was 0.90 (95% CI 0.85–0.95) for symptomatic women. Study limitations included a lack of compliance with national guidance at the control sites and difficulties in implementation of the QUiPP app. Conclusions This cluster randomised trial did not demonstrate that the use of the QUiPP app reduced unnecessary management of TPTL compared to current management but would safely improve the management recommended by the National Institute for Health and Care Excellence (NICE). Interpretation of qfFN, with or without the QUiPP app, is a safe and accurate method for identifying women most likely to benefit from PTL interventions. Trial registration ISRCTN Registry ISRCTN17846337.

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All the right moves: why in utero transfer is both important for the baby and difficult to achieve and new strategies for change

F1000Research ◽

10.12688/f1000research.25923.1 ◽

2020 ◽

Vol 9 ◽

pp. 979

Author(s):

Helena Watson ◽

James McLaren ◽

Naomi Carlisle ◽

Nandiran Ratnavel ◽

Tim Watts ◽

...

Keyword(s):

Preterm Birth ◽

Transfer Process ◽

Assisted Reproductive Technologies ◽

Clinical Care ◽

Multiple Pregnancy ◽

Reproductive Technologies ◽

In Utero ◽

The Uk ◽

The Right ◽

The Impact

The best way to ensure that preterm infants benefit from relevant neonatal expertise as soon as they are born is to transfer the mother and baby to an appropriately specialised neonatal facility before birth (“in utero”). This review explores the evidence surrounding the importance of being born in the right unit, the advantages of in utero transfers compared to ex utero transfers, and how to accurately assess which women are at most risk of delivering early and the challenges of in utero transfers. Accurate identification of the women most at risk of preterm birth is key to prioritising who to transfer antenatally, but the administrative burden and pathway variation of in utero transfer in the UK are likely to compromise optimal clinical care. Women reported the impact that in utero transfers have on them, including the emotional and financial burdens of being transferred and the anxiety surrounding domestic and logistical concerns related to being away from home. The final section of the review explores new approaches to reforming the in utero transfer process, including learning from outside the UK and changing policy and guidelines. Examples of collaborative regional guidance include the recent Pan-London guidance on in utero transfers. Reforming the transfer process can also be aided through technology, such as utilising the CotFinder app. In utero transfer is an unavoidable aspect of maternity and neonatal care, and the burden will increase if preterm birth rates continue to rise in association with increased rates of multiple pregnancy, advancing maternal age, assisted reproductive technologies, and obstetric interventions. As funding and capacity pressures on health services increase because of the COVID-19 pandemic, better prioritisation and sustained multi-disciplinary commitment are essential to maximise better outcomes for babies born too soon.

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In Utero Antihypertensive Medication Exposure and Neonatal Outcomes

Hypertension ◽

10.1161/hypertensionaha.119.13802 ◽

2020 ◽

Vol 75 (3) ◽

pp. 628-633

Author(s):

Catherine A. Fitton ◽

Michael Fleming ◽

Markus F.C. Steiner ◽

Lorna Aucott ◽

Jill P. Pell ◽

...

Keyword(s):

Birth Weight ◽

Preterm Birth ◽

Low Birth Weight ◽

Gestational Age ◽

Small For Gestational Age ◽

Antihypertensive Medication ◽

Late Onset ◽

In Utero ◽

Medication Exposure ◽

Untreated Hypertension

Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment. Data describing the safety of in utero exposure to antihypertensive treatment is conflicting, with many studies suffering from significant methodological issues, such as inappropriate study design, small sample sizes, and no untreated control group. We conducted a retrospective cohort study using linked routinely collected healthcare records for 268 711 children born 2010–2014 in Scotland to assess outcomes following in utero exposure to antihypertensive medication. We identified a cohort of 265 488 eligible children born over the study period; of which, 2350 were exposed to in utero antihypertensive medication, 4391 exposed to treated late-onset hypertension, and 7971 exposed to untreated hypertension during pregnancy. Untreated hypertension was associated with increased risk of preterm birth (adjusted risk ratio [aRR], 1.15 [99% CI, 1.01–1.30]), low birth weight (aRR, 2.01 [99% CI, 1.72–2.36]) and being small for gestational age (aRR, 1.50 [99% CI, 1.35–1.66]), while in utero antihypertensive exposure was also associated with preterm birth (aRR, 3.12 [99% CI, 2.68–3.64]), low birth weight (aRR, 2.23 [99% CI, 1.79–2.78]), and being small for gestational age (aRR, 2.13 [99% CI, 1.81–2.52]). Late-onset hypertension was also associated with preterm birth (aRR, 2.21 [99% CI, 1.86–2.62]), low birth weight (aRR, 2.06 [99% CI, 1.74–2.43]), and being small for gestational age (aRR, 1.90 [99% CI, 1.68–2.16]). Our results suggest that hypertension is a key risk factor for low birth weight and preterm birth. Although preterm birth may be associated with antihypertensive medication exposure during pregnancy, these associations may reflect increasing hypertension severity necessitating treatment.

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Preterm birth and selection in utero among males following the November 2015 Paris attacks

International Journal of Epidemiology ◽

10.1093/ije/dyz089 ◽

2019 ◽

Vol 48 (5) ◽

pp. 1614-1622 ◽

Cited By ~ 2

Author(s):

Tim A Bruckner ◽

Élodie Lebreton ◽

Natalie Perrone ◽

Laust H Mortensen ◽

Béatrice Blondel

Keyword(s):

Preterm Birth ◽

Serial Correlation ◽

Preterm Births ◽

Interrupted Time Series ◽

In Utero ◽

Risk Difference ◽

Terrorist Attacks ◽

Live Births ◽

Sensitivity Tests ◽

The Usa

Abstract Background On 13 November 2015, coordinated terrorist attacks swept through Paris. This large stressor, like earlier terrorist attacks in the USA, may have perturbed the health of pregnant women. We test whether the attacks preceded an increase in the risk of preterm parturition among live-born males as well as excess male loss in utero. We focused on males on the basis of previous findings of elevated male frailty following population stressors. Methods We examined live births in the Paris region (n = 1 049 057) over 70 months, from January 2011 to October 2016. Interrupted time-series methods identified and removed serial correlation in the monthly risk of preterm birth; these methods employed non-linear least-squares estimation. We also repeated analyses using month of conception, and performed sensitivity tests among females as well as among male births outside Paris. Results Males exhibited an elevated incidence of preterm birth in November 2015 and January 2016 [risk difference for November 2015 = 0.006, 95% confidence interval (CI): 0.0002—0.012; risk difference for January 2016 = 0.010, 95% CI: 0.004—0.016], which equates to an 11% increase in the count of preterm births. Females, as well as males born outside Paris, showed no change in preterm delivery. The sex ratio also fell below expected values in December 2015, January 2016 and February 2016. Conclusions Among males, more preterm births, but fewer live births, occurred after the November 2015 Paris attacks. Future examinations of perinatal health responses to unexpected stressors may benefit from sex-specific analyses.

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