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Non-invasive prenatal testing (NIPT) is a widely adopted maternal blood test that analyses foetal originating DNA to screen for foetal chromosomal conditions, including Down's syndrome (DS). The introduction of this test, which may have implications for important decisions made during pregnancy, requires continual monitoring and evaluation. This systematic review aims to assess the extent of NIPT introduction into national screening programmes for DS worldwide, its uptake, and impact on pregnancy outcomes. The study protocol was published in PROSPERO (CRD42022306167). We systematically searched MEDLINE, CINAHL, Scopus, and Embase for population-based studies, government guidelines, and Public Health documents from 2010 onwards. Results summarised the national policies for NIPT implementation into screening programmes geographically, along with population uptake. Meta-analyses estimated the pooled proportions of women choosing invasive prenatal diagnosis (IPD) following a high chance biochemical screening result, before and after NIPT was introduced. Additionally, we meta-analysed outcomes (termination of pregnancy and live births) amongst high chance pregnancies identified by NIPT. Results demonstrated NIPT implementation in at least 27 countries. Uptake of second line NIPT varied, from 20.4% to 93.2% (n = 6). Following NIPT implementation, the proportion of women choosing IPD after high chance biochemical screening decreased from 75% (95% CI 53%, 88%, n = 5) to 43% (95%CI 31%, 56%, n = 5), an absolute risk reduction of 38%. A pooled estimate of 69% (95% CI 52%, 82%, n = 7) of high chance pregnancies after NIPT resulted in termination, whilst 8% (95% CI 3%, 21%, n = 7) had live births of babies with DS. NIPT has rapidly gained global acceptance, but population uptake is influenced by healthcare structures, historical screening practices, and cultural factors. Our findings indicate a reduction in IPD tests following NIPT implementation, but limited pre-NIPT data hinder comprehensive impact assessment. Transparent, comparable data reporting is vital for monitoring NIPT's potential consequences.

Despite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age. We searched the major electronic databases Medline, Embase, and Google Scholar (January 1990-October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95% confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95% CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95% CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95% CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome. Our findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks. PROSPERO CRD42015013785.

Mairead Black and Sohinee Bhattacharya discuss research findings on preferences for cesarean delivery in Asian settings and share their Perspective on facilitating woman-centered birth choices in China following the end of the one-child policy.

ObjectiveWeight management interventions during pregnancy have had limited success in reducing the risk of pregnancy complications. Focus has now shifted to pre-pregnancy counselling to optimise body weight before subsequent conception. We aimed to assess the effect of interpregnancy body mass index (BMI) change on the risk of perinatal complications in the second pregnancy.MethodsA cohort study was performed using pooled maternity data from Aberdeen, Finland and Malta. Women with a BMI change of ±2 kg/m2 between their first and second pregnancies were compared with those who were BMI stable (remained within ±2 kg/m2). Outcomes assessed included pre-eclampsia (PE), intrauterine growth restriction (IUGR), preterm birth, birth weight, and stillbirth in the second pregnancy. We also assessed the effect of unit change in BMI for PE and IUGR. Logistic regression was used to calculate odds ratios with 95% confidence intervals.ResultsAn increase of ≥2 kg/m2 between the first two pregnancies increased the risk of PE (1.66 (1.49–1.86)) and high birthweight (>4000 g) (1.06 (1.03–1.10)). A reduction of ≥2 kg/m2 increased the chance of IUGR (1.15 (1.01–1.31)) and preterm birth (1.14 (1.01–1.30)), while reducing the risk of instrumental delivery (0.75 (0.68–0.85)) and high birthweight (0.93 (0.87–0.98)). Reducing BMI did not significantly decrease PE risk in women with obesity or those with previous PE. A history of PE or IUGR in the first pregnancy was the strongest predictor of recurrence independent of interpregnancy BMI change (5.75 (5.30–6.24) and (7.44 (6.71–8.25), respectively).ConclusionChanges in interpregnancy BMI have a modest impact on the risk of high birthweight, PE and IUGR in contrasting directions. However, a prior history of PE and IUGR is the dominant predictor of recurrence at second pregnancy.

Aims/hypothesisMaternal obesity in pregnancy is associated with cardiovascular disease and mortality rate in the offspring. We aimed to determine whether maternal obesity is also associated with increased incidence of type 2 and type 1 diabetes in the offspring, independently of maternal diabetes as a candidate mechanistic pathway.MethodsBirth records of 118,201 children from 1950 to 2011 in the Aberdeen Maternity and Neonatal Databank were linked to Scottish Care Information–Diabetes, the national register for diagnosed diabetes in Scotland, to identify incident and prevalent type 1 and type 2 diabetes up to 1 January 2012. Maternal BMI was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on offspring outcomes was tested using time-to-event analysis with Cox proportional hazards regression to compare outcomes in offspring of mothers in underweight, overweight or obese categories of BMI, compared with offspring of women with normal BMI.ResultsOffspring of obese (BMI ≥30 kg/m2) and overweight (BMI 25–29.9 kg/m2) mothers had an increased hazard of type 2 diabetes compared with mothers with normal BMI, after adjustment for gestation when weight was measured, maternal history of diabetes before pregnancy, maternal history of hypertension, age at delivery, parity, socioeconomic status, and sex of the offspring: HR 3.48 (95% CI 2.33, 5.06) and HR 1.39 (1.06, 1.83), respectively.Conclusions/interpretationMaternal obesity is associated with increased incidence of type 2 diabetes in the offspring. Evidence-based strategies that reduce obesity among women of reproductive age and that might reduce the incidence of diabetes in their offspring are urgently required.

Maternal obesity in pregnancy predicts offspring psychopathology risk in childhood but it remains unclear whether maternal obesity or underweight associate with adult offspring mental disorders. We examined longitudinally whether maternal body mass index (BMI) in pregnancy predicted mental disorders in her offspring and whether the associations differed by offspring birth year among 68,571 mother–child dyads of Aberdeen Maternity and Neonatal Databank, Scotland. The offspring were born 1950–1999. Maternal BMI was measured at a mean 15.7 gestational weeks and classified into underweight, normal weight, overweight, moderate obesity and severe obesity. Mental disorders were identified from nationwide registers carrying diagnoses of all hospitalizations and deaths in Scotland in 1996–2017. We found that maternal BMI in pregnancy was associated with offspring mental disorders in a time-dependent manner: In offspring born 1950–1974, maternal underweight predicted an increased hazard of mental disorders [Hazard Ratio (HR) = 1.74; 95% Confidence Interval (CI) = 1.01–3.00)]. In offspring born 1975–1999, maternal severe obesity predicted increased hazards of any mental (HR 1.60; 95% CI 1.08–2.38) substance use (HR 1.91; 95% CI 1.03–3.57) and schizophrenia spectrum (HR 2.80; 95% CI 1.40–5.63) disorders. Our findings of time-specific associations between maternal prenatal BMI and adult offspring mental disorders may carry important public health implications by underlining possible lifelong effects of maternal BMI on offspring psychopathology.

Policy consensus in high-income countries supports offering pregnant women with previous cesarean section a choice between planning an elective repeat cesarean section (ERCS) or attempting a vaginal birth, known as a planned vaginal birth after previous cesarean (VBAC), provided they do not have contraindications to planned VBAC. However, robust comprehensive information on the associated outcomes to counsel eligible women about this choice is lacking. This study investigated the short-term maternal and perinatal outcomes associated with planned mode of delivery after previous cesarean section among women delivering a term singleton and considered eligible to have a planned VBAC. A population-based cohort of 74,043 term singleton births in Scotland between 2002 and 2015 to women with one or more previous cesarean sections was conducted using linked Scottish national datasets. Logistic or modified Poisson regression, as appropriate, was used to estimate the effect of planned mode of delivery on maternal and perinatal outcomes adjusted for sociodemographic, maternal medical, and obstetric-related characteristics. A total of 45,579 women gave birth by ERCS, and 28,464 had a planned VBAC, 28.4% of whom went on to have an in-labor nonelective repeat cesarean section. Compared to women delivering by ERCS, those who had a planned VBAC were significantly more likely to have uterine rupture (0.24%, n = 69 versus 0.04%, n = 17, adjusted odds ratio [aOR] 7.3, 95% confidence interval [CI] 3.9-13.9, p < 0.001), a blood transfusion (1.14%, n = 324 versus 0.50%, n = 226, aOR 2.3, 95% CI 1.9-2.8, p < 0.001), puerperal sepsis (0.27%, n = 76 versus 0.17%, n = 78, aOR 1.8, 95% CI 1.3-2.7, p = 0.002), and surgical injury (0.17% versus 0.09%, n = 40, aOR 3.0, 95% CI 1.8-4.8, p < 0.001) and experience adverse perinatal outcomes including perinatal death, admission to a neonatal unit, resuscitation requiring drugs and/or intubation, and an Apgar score < 7 at 5 minutes (7.99%, n = 2,049 versus 6.37%, n = 2,570, aOR 1.6, 95% CI 1.5-1.7, p < 0.001). However, women who had a planned VBAC were more likely than those delivering by ERCS to breastfeed at birth or hospital discharge (63.6%, n = 14,906 versus 54.5%, n = 21,403, adjusted risk ratio [aRR] 1.2, 95% CI 1.1-1.2, p < 0.001) and were more likely to breastfeed at 6-8 weeks postpartum (43.6%, n = 10,496 versus 34.5%, n = 13,556, aRR 1.2, 95% CI 1.2-1.3, p < 0.001). The effect of planned mode of delivery on the mother's risk of having a postnatal stay greater than 5 days, an overnight readmission to hospital within 42 days of birth, and other puerperal infection varied according to whether she had any prior vaginal deliveries and, in the case of length of postnatal stay, also varied according to the number of prior cesarean sections. The study is mainly limited by the potential for residual confounding and misclassification bias. Among women considered eligible to have a planned VBAC, planned VBAC compared to ERCS is associated with an increased risk of the mother having serious birth-related maternal and perinatal complications. Conversely, planned VBAC is associated with an increased likelihood of breastfeeding, whereas the effect on other maternal outcomes differs according to whether a woman has any prior vaginal deliveries and the number of prior cesarean sections she has had. However, the absolute risk of adverse outcomes is small for either delivery approach. This information can be used to counsel and manage the increasing number of women with previous cesarean section, but more research is needed on longer-term outcomes.

This study aimed to investigate the reproductive impact of a third- or fourth-degree tear in primigravid women. A retrospective population-based cohort study was conducted using data from Scottish Morbidity Records (SMR02). Primigravid women with a vaginal birth in Scotland from 1997 until 2010 were included. Exposure was third- or fourth-degree tear in the first pregnancy. The second pregnancy rate, interpregnancy interval and third- or fourth-degree tear in a second pregnancy were the primary outcomes. A nested case-control study was used to determine factors associated with repeat third- or fourth-degree tears in a second vaginal birth. Cox regression analysis and logistic regression were used to look for associations. Initial third- or fourth-degree tear occurred in 2.8% women (5174/182445). The percentage of third- or fourth-degree tears in first vaginal births increased from 1% in 1997 to 4.9% in 2010. There was no difference in having a second pregnancy (adjusted Odds Ratio (aOR) 0.98 (99%CI 0.89-1.09)) or the median interpregnancy interval to second pregnancy (adjusted Hazard Ratio (aHR) 1.01 (99%CI 0.95-1.08)) after an initial third- or fourth-degree tear. Women were over four times more likely to have a repeat injury in a subsequent vaginal birth (n = 149/333, aOR 4.68 (99% 3.52-6.23)) and were significantly more likely to have an elective caesarean section in their second pregnancy (n = 887/3333, 26.6%; 12.75 (11.29-14.40)). Increased maternal age and birthweight ≥4500g were risk factors for repeat injury. Third- and fourth-degree tears are increasing in Scotland. Women do not delay or avoid childbirth after initial third- or fourth-degree tear. However, women are more likely to have a repeat third- or fourth-degree tear or an elective caesarean section in the second pregnancy. Strategies to prevent third- or fourth-degree tears are needed.

ObjectivesTo identify any associations between in utero exposure to five over-the-counter (non-prescription) analgesics (paracetamol, ibuprofen, aspirin, diclofenac, naproxen) and adverse neonatal outcomes.DesignRetrospective cohort study using the Aberdeen Maternity and Neonatal Databank.Participants151 141 singleton pregnancies between 1985 and 2015.Main outcome measuresPremature delivery (<37 weeks), stillbirth, neonatal death, birth weight, standardised birthweight score, neonatal unit admission, APGAR score at 1 and 5 min, neural tube and amniotic band defects, gastroschisis and, in males, cryptorchidism and hypospadias.Results83.7% of women taking over-the-counter analgesics reported first trimester use when specifically asked about use at their first antenatal clinic visit. Pregnancies exposed to at least one of the five analgesics were significantly independently associated with increased risks for premature delivery <37 weeks (adjusted OR (aOR)=1.50, 95% CI 1.43 to 1.58), stillbirth (aOR=1.33, 95% CI 1.15 to 1.54), neonatal death (aOR=1.56, 95% CI 1.27 to 1.93), birth weight <2500 g (aOR=1.28, 95% CI 1.20 to 1.37), birth weight >4000 g (aOR=1.09, 95% CI 1.05 to 1.13), admission to neonatal unit (aOR=1.57, 95% CI 1.51 to 1.64), APGAR score <7 at 1 min (aOR=1.18, 95% CI 1.13 to 1.23) and 5 min (aOR=1.48, 95% CI 1.35 to 1.62), neural tube defects (aOR=1.64, 95% CI 1.08 to 2.47) and hypospadias (aOR=1.27, 95% CI 1.05 to 1.54 males only). The overall prevalence of over-the-counter analgesics use during pregnancy was 29.1%, however it rapidly increased over the 30-year study period, to include over 60% of women in the last 7 years of the study. This makes our findings highly relevant to the wider pregnant population.ConclusionsOver-the-counter (non-prescription) analgesics consumption during pregnancy was associated with a substantially higher risk for adverse perinatal health outcomes in the offspring. The use of paracetamol in combination with other non-steroidal anti-inflammatory drugs conferred the highest risk. The increased risks of adverse neonatal outcomes associated with non-prescribed, over-the-counter, analgesics use during pregnancy indicate that healthcare guidance for pregnant women regarding analgesic use need urgent updating.

[This corrects the article DOI: 10.1371/journal.pone.0298643.].