Background Preterm birth is the leading cause of child mortality globally, with many survivors experiencing long-term adverse consequences. Preliminary evidence suggests that numbers of preterm births greatly reduced following implementation of policy measures aimed at mitigating the effects of the COVID-19 pandemic. We aimed to study the impact of the COVID-19 mitigation measures implemented in the Netherlands in a stepwise fashion on March 9, March 15, and March 23, 2020, on the incidence of preterm birth.Methods We used a national quasi-experimental difference-in-regression-discontinuity approach. We used data from the neonatal dried blood spot screening programme (2010−20) cross-validated against national perinatal registry data. Stratified analyses were done according to gestational age subgroups, and sensitivity analyses were done to assess robustness of the findings. We explored potential effect modification by neighbourhood socioeconomic status, sex, and small-for-gestational-age status. FindingsData on 1 599 547 singleton neonates were available, including 56 720 births that occurred after implementation of COVID-19 mitigation measures on March 9, 2020. Consistent reductions in the incidence of preterm birth were seen across various time windows surrounding March 9 (± 2 months [n=531 823] odds ratio [OR] 0•77, 95% CI 0•66-0•91, p=0•0026; ± 3 months [n=796 531] OR 0•85, 0•73-0•98, p=0•028; ± 4 months [n=1 066 872] OR 0•84, 0•73-0•97, p=0•023). Decreases in incidence observed following the March 15 measures were of smaller magnitude, but not statistically significant. No changes were observed after March 23. Reductions in the incidence of preterm births after March 9 were consistent across gestational age strata and robust in sensitivity analyses. They appeared confined to neighbourhoods of high socioeconomic status, but effect modification was not statistically significant.Interpretation In this national quasi-experimental study, initial implementation of COVID-19 mitigation measures was associated with a substantial reduction in the incidence of preterm births in the following months, in agreement with preliminary observations elsewhere. Integration of comparable data from across the globe is needed to further substantiate these findings and start exploring underlying mechanisms.

In a systematic review and meta-analysis, Jasper Been and colleagues investigate the association between preterm birth and the development of wheezing disorders in childhood. Please see later in the article for the Editors' Summary

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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.

SummaryBackgroundTobacco smoking and smoke exposure during pregnancy and childhood cause considerable childhood morbidity and mortality. We did a systematic review and meta-analysis to investigate whether implementation of WHO's recommended tobacco control policies (MPOWER) was of benefit to perinatal and child health.MethodsWe searched 19 electronic databases, hand-searched references and citations, and consulted experts to identify studies assessing the association between implementation of MPOWER policies and child health. We did not apply any language restrictions, and searched the full time period available for each database, up to June 22, 2017. Our primary outcomes of interest were perinatal mortality, preterm birth, hospital attendance for asthma exacerbations, and hospital attendance for respiratory tract infections. Where possible and appropriate, we combined data from different studies in random-effects meta-analyses. This study is registered with PROSPERO, number CRD42015023448.FindingsWe identified 41 eligible studies (24 from North America, 16 from Europe, and one from China) that assessed combinations of the following MPOWER policies: smoke-free legislation (n=35), tobacco taxation (n=11), and smoking cessation services (n=3). Risk of bias was low in 23 studies, moderate in 16, and high in two. Implementation of smoke-free legislation was associated with reductions in rates of preterm birth (–3·77% [95% CI −6·37 to −1·16]; ten studies, 27 530 183 individuals), rates of hospital attendance for asthma exacerbations (–9·83% [–16·62 to −3·04]; five studies, 684 826 events), and rates of hospital attendance for all respiratory tract infections (–3·45% [–4·64 to −2·25]; two studies, 1 681 020 events) and for lower respiratory tract infections (–18·48% [–32·79 to −4·17]; three studies, 887 414 events). Associations appeared to be stronger when comprehensive smoke-free laws were implemented than when partial smoke-free laws were implemented. Among two studies assessing the association between smoke-free legislation and perinatal mortality, one showed significant reductions in stillbirth and neonatal mortality but did not report the overall effect on perinatal mortality, while the other showed no change in perinatal mortality. Meta-analysis of studies on other MPOWER policies was not possible; all four studies on increasing tobacco taxation and one of two on offering disadvantaged pregnant women help to quit smoking that reported on our primary outcomes had positive findings. Assessment of publication bias was only possible for studies assessing the association between smoke-free legislation and preterm birth, showing some degree of bias.InterpretationSmoke-free legislation is associated with substantial benefits to child health. The majority of studies on other MPOWER policies also indicated a positive effect. These findings provide strong support for implementation of such policies comprehensively across the world.FundingChief Scientist Office Scotland, Farr Institute, Netherlands Lung Foundation, Erasmus...

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.

Currently available evidence supports a role for antenatal inflammation in NEC pathophysiology. This finding emphasizes the need to further study the underlying mechanisms and evaluate potential interventions to improve postnatal intestinal outcomes.

Periodontal disease is very common during pregnancy. Although it has been linked to adverse pregnancy outcomes, systematic reviews have reached discrepant conclusions on these links. Therefore, we conducted a systematic overview of systematic reviews studying the association between periodontal disease and adverse pregnancy outcomes. We searched 6 online databases up to November 2016 and hand-searched references and citations of eligible papers. Systematic reviews of studies comparing pregnancy outcomes among women with and without periodontal disease were eligible for inclusion. Primary outcomes were maternal mortality, preterm birth, and perinatal mortality. Two reviewers extracted data and assessed risk of bias of individual systematic reviews. Findings are described in tabular and narrative form. Twenty-three systematic reviews (including between 3 and 45 studies) were included. None reported the association between periodontal disease and maternal or perinatal mortality. Systematic reviews with the lowest risk of bias consistently demonstrated positive associations between periodontal disease and preterm birth (relative risk, 1.6; 95% confidence interval, 1.3 to 2.0; 17 studies, 6,741 participants), low birth weight (LBW; relative risk, 1.7; 95% CI, 1.3 to 2.1; 10 studies, 5,693 participants), preeclampsia (odds ratio, 2.2; 95% CI, 1.4 to 3.4; 15 studies, 5,111 participants), and preterm LBW (relative risk 3.4; 95% CI, 1.3 to 8.8; 4 studies, 2,263 participants). Based on these figures, estimated population-attributable fractions for periodontal disease were 5% to 38% for preterm birth, 6% to 41% for LBW, and 10% to 55% for preeclampsia. In terms of limitations, as several primary studies did not adjust for confounding, meta-analyses may have overestimated the strength of the associations under study. Due to substantial overlap in included primary studies, we could not aggregate results across reviews. Consistent evidence from systematic reviews with low risk of bias indicates that pregnant women with periodontal disease are at increased risk of developing preeclampsia and delivering a preterm and/or LBW baby (PROSPERO: CRD42015030132).Knowledge Transfer Statement: This study highlights that periodontal disease is an important risk factor for several common adverse pregnancy outcomes. Clinicians should be aware of this link to guide risk selection. Research is needed to develop novel preventive and treatment strategies.