Embryonic size and growth and adverse birth outcomes: the Rotterdam Periconception Cohort.

STUDY QUESTION: Is early embryonic size and growth in the first trimester of pregnancy associated with adverse birth outcomes? SUMMARY ANSWER: Larger embryonic crown-rump length (CRL) and embryonic volume (EV) are associated with lower odds of adverse birth outcomes, especially small for gestational age (SGA). WHAT IS ALREADY KNOWN: Preterm birth, SGA, and congenital anomalies are the most prevalent adverse birth outcomes with lifelong health consequences as well as high medical and societal costs. In the late first and second trimesters of pregnancy, fetuses at risk for adverse birth outcomes can be identified using 2-dimensional ultrasonography (US). STUDY DESIGN, SIZE, DURATION: Between 2009 and 2018, singleton pregnancies were enrolled in this ongoing prospective Rotterdam Periconception Cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included 918 pregnant women from a tertiary hospital in the Netherlands. Pregnancy dating was based on either a regular menstrual cycle (for natural pregnancies) or a conception date (for ART pregnancies). CRL and EV were measured using Virtual Reality software on 3-dimensional (3D) ultrasound scans, repeatedly performed around 7, 9, and 11 weeks of gestation. The main outcome measure was adverse birth outcome, defined as the composite of SGA (birth weight <10th percentile), preterm birth (<37th week of gestation), congenital anomalies (Eurocat criteria), stillbirth (>16th week of pregnancy), or early neonatal mortality (≤7 days of life). Reference curves for CRL and EV were constructed. Cross-sectional (CRL/EV <20th percentile at 7, 9, and 11 weeks of gestation) and longitudinal (CRL/EV growth trajectories between 6th and 13th weeks) regression analyses were performed, with adjustments for the participants' educational level, smoking, parity, age, BMI, geographical background, mode of conception, and fetal sex. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 918 pregnant women included, the median age was 32.3 years, and 404 (44%) pregnancies had been conceived via ART. In 199 (22%) pregnancies, there was an adverse birth outcome. Regression analyses showed that at 7 weeks of gestation onwards, embryos with a CRL <20th percentile had an ∼2-fold increased odds of adverse birth outcome (adjusted odds ratio (aOR) 2.03, 95% CI 1.21-3.39, P = 0.007). Similar associations were found for EV <20th percentile but were not statistically significant. These findings were mainly driven by the strong association between embryonic size and SGA (e.g. 7-week CRL: aOR 2.18 (1.16-4.09), P = 0.02; 9-week EV: aOR 2.09 (1.10-3.97, P = 0.02). Longitudinal growth trajectories of CRL, but not of EV, were associated with adverse birth outcomes. Both CRL and EV growth trajectories were associated with SGA. LIMITATIONS, REASONS FOR CAUTION: The tertiary hospital population and the availability of sophisticated 3D-ultrasound techniques limit the generalizability of this study to general populations and settings. WIDER IMPLICATIONS OF THE FINDINGS: Already very early in the first trimester of pregnancy, embryos with increased risks of an adverse birth outcome can be identified by using 3D-US and Virtual Reality. This expands the window of opportunity to enable the development of future interventions to potentially improve pregnancy outcomes and offspring health during their life-course. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: NL4115.

Effect of COVID-19 lockdown on maternity care and maternal outcome in the Netherlands: a national quasi-experimental study.

OBJECTIVES: The COVID-19 pandemic and associated lockdowns disrupted health care worldwide. High-income countries observed a decrease in preterm births during lockdowns, but maternal pregnancy-related outcomes were also likely affected. This study investigates the effect of the first COVID-19 lockdown (March-June 2020) on provision of maternity care and maternal pregnancy-related outcomes in the Netherlands. STUDY DESIGN: National quasi-experimental study. METHODS: Multiple linked national registries were used, and all births from a gestational age of 24+0 weeks in 2010-2020 were included. In births starting in midwife-led primary care, we assessed the effect of lockdown on provision of care. In the general pregnant population, the impact on characteristics of labour and maternal morbidity was assessed. A difference-in-regression-discontinuity design was used to derive causal estimates for the year 2020. RESULTS: A total of 1,039,728 births were included. During the lockdown, births to women who started labour in midwife-led primary care (49%) more often ended at home (27% pre-lockdown, +10% [95% confidence interval: +7%, +13%]). A small decrease was seen in referrals towards obstetrician-led care during labour (46%, -3% [-5%,-0%]). In the overall group, no significant change was seen in induction of labour (27%, +1% [-1%, +3%]). We found no significant changes in the incidence of emergency caesarean section (9%, -1% [-2%, +0%]), obstetric anal sphincter injury (2%, +0% [-0%, +1%]), episiotomy (21%, -0% [-2%, +1%]), or post-partum haemorrhage: >1000 ml (6%, -0% [-1%, +1%]). CONCLUSIONS: During the first COVID-19 lockdown in the Netherlands, a substantial increase in homebirths was seen. There was no evidence for changed available maternal outcomes, suggesting that a maternity care system with a strong midwife-led primary care system may flexibly and safely adapt to external disruptions.

Client-tailored maternity care to increase maternal empowerment: cluster randomized controlled trial protocol; the healthy pregnancy 4 All-2 program.

BACKGROUND: The postpartum period is an important period for preventive strategies as common maternal and child health risks may become manifest. Women with a lower socioeconomic status tend to have lower maternal empowerment. Increasing their risks of adverse maternal and child health outcomes. This study aims to assess the effectiveness of a primary care level intervention. Delivered to maternity care assistants, aiming to increase maternal empowerment postpartum. METHODS: This study is part of the Dutch nationwide "Healthy Pregnancy 4 All-2" (HP4All-2) program, which aims to identify vulnerable mothers and young children at risk of adverse health outcomes, and subsequently improve their care. This program targets women from deprived neighborhoods. A pragmatic cluster randomized controlled trial will be undertaken in 12 maternity care organizations. Maternity care organizations in urban municipalities (i.e. the clusters) will be randomized to either a systematic risk assessment during pregnancy with emphasis on identification of non-medical risk factors for adverse maternal and neonatal health outcomes, and subsequent adaptation of care towards a client-tailored approach during pregnancy and the postpartum period, or solely the systematic risk assessment. The primary outcome is the prevalence of a low maternal empowerment score postpartum. Secondary maternal outcomes cover health-related quality of life, postnatal depression, smoking, alcohol consumption, illicit drug use. Finally, maternal and neonatal health care utilization postpartum are recorded. All outcomes will be analyzed according to the intention-to-treat principle, using multi-level mixed effects models. DISCUSSION: The study will contribute to evidence regarding the effectiveness of client-tailored, risk-based maternity care to increase maternal empowerment postpartum. TRIAL REGISTRATION: Netherlands Trial Registry (NTR) 6311 , registered 03-27-2017.

[Tobacco control policies and perinatal health]. / Tabaksontmoediging en perinatale gezondheid.

OBJECTIVE: Study the association between the introduction of tobacco control policies in the Netherlands and changes in perinatal outcomes. DESIGN: National quasi-experimental study. METHOD: We used Netherlands Perinatal Registry data (now called Perined) for the period 2000-2011. We studied whether the introduction of smoke-free legislation in workplaces plus a tobacco tax increase and mass media campaign in January 2004, and extension of the smoke-free law to the hospitality industry accompanied by another tax increase and media campaign in July 2008, was associated with changes in perinatal outcomes. We studied all singleton births (gestational age: 24+0 to 42+6 weeks). Our primary outcome measures were: perinatal mortality, preterm birth and being small-for-gestational-age (SGA). Interrupted time series logistic regression analyses were performed to investigate changes in these outcomes occurred after the introduction of the aforementioned tobacco control policies (ClinicalTrials.gov: NCT02189265). RESULTS: Among 2,069,695 singleton births, 13,027 (0.6%) perinatal deaths, 116,043 (5.6%) preterm live-births and 187,966 (9.1%) SGA live-births were observed. The policies introduced in January 2004 were not associated with significant changes in any of the primary outcome measures. A -4.4% (95% CI: -6.4 to -2.4; p < 0.001) decrease in odds of a SGA birth was observed after the policy extension in July 2008 to include a smoke-free hospitality industry, a further tax increase and another media campaign. This translates to an estimated over 500 cases of SGA being averted per year. CONCLUSION: A reduction in SGA births, but not preterm birth or perinatal mortality, was observed in the Netherlands after extension of the smoke-free workplace law to include bars and restaurants, in conjunction with a tax increase and media campaign in 2008.

[The effects of smoking on health: growth of knowledge reveals even grimmer picture]. / De gezondheidseffecten van roken.

- In this article we give a short overview of new insights into the effects of smoking on health, both on smokers themselves and on those who are exposed to other people's tobacco smoke.- The number of diseases and conditions that are known to be caused by active smoking has now risen to over thirty.- The risk of premature death is not, as previously thought, twice as high in smokers as in non-smokers, but actually three times as high.- Passive smoking too has been shown to have a whole range of negative effects on health.- Further, the causal mechanisms of, amongst other things, the development of cancer, ischaemic heart disease and nicotine dependence under the influence of smoking have been largely unravelled.- Various issues require further investigation; these include the effect of smoking on psychological health and the effects of 'third-hand' smoke. In the meantime, a concerted campaign against this consumer product with its deleterious effects of the health of the population is overdue.

Chorioamnionitis: a multiorgan disease of the fetus?

The bacterial infection of chorion and amnion is a common finding in premature delivery and is referred to as chorioamnionitis. As the mother rarely shows symptoms of a systemic inflammation, the course of chorioamnionitis is frequently asymptomatic and chronic. In contrast, the fetal inflammatory response syndrome represents a separate phenomenon, including umbilical inflammation and increased serum levels of proinflammatory cytokines in the fetus. Ascending maternal infections frequently lead to systemic fetal inflammatory reaction. Clinical studies have shown that antenatal exposure to inflammation puts the extremely immature neonates at a high risk for worsening pulmonary, neurological and other organ development. Interestingly, the presence of chorioamnionitis is associated with a lower rate of neonatal mortality in extremely immature newborns. In the following review, the pathogeneses of inflammation-associated perinatal morbidity are outlined. The concept of fetal multiorganic disease during intrauterine infection is introduced and discussed.

Histological chorioamnionitis and respiratory outcome in preterm infants.

A considerable body of human and animal experimental evidence links antenatal inflammation to both accelerated maturation and adverse development of the lung. Initial reports suggest that in preterm infants histological chorioamnionitis is associated with a decreased incidence of respiratory distress syndrome (RDS), while the incidence of bronchopulmonary dysplasia (BPD) is increased. Considerable variation exists in the findings of subsequent human studies, largely dependent on differences in inclusion and exclusion criteria. Taking these differences into account, recent studies generally seem to confirm the effect of chorioamnionitis on RDS incidence, while no effect on BPD is seen. The increased use of antenatal steroids and the diminished effects of secondary pro-inflammatory hits seem to explain part of this change. Additional research is needed to explore these complex interactions and their underlying mechanisms, and evaluate the long term pulmonary effects of antenatal inflammation.